Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli bacteraemia can induce unfavorable clinical outcomes due to delay in appropriate antimicrobial treatment and the limited therapeutic options. Therefore, elucidating the predictors of ESBL-producing E. coli-induced bacteraemia is crucial for improving clinical outcomes. However, a literature search did not reveal any study that incorporates a meta-analysis of the predictors of ESBL-producing E. coli-induced bacteraemia. This review assessed the current evidence on the predictors of ESBL-producing E. coli-induced bacteraemia. METHODS: The PubMed, Web of Science, and Cochrane Library databases were searched for all relevant publications from January 2000 to September 2021. RESULTS: In this systematic review of 10 observational studies, comprising a total of 2325 patients with E. coli-induced bacteraemia and 850 (36.6%) ESBL-producing strains, were evaluated. In the meta-analysis, previous antibiotic therapy (pooled risk ratio [RR], 2.72; p < 0.001), especially cephalosporins (pooled RR, 4.66; p < 0.001) and quinolones (pooled RR, 5.47; p < 0.001), and urinary catheter use (pooled RR, 3.79; p < 0.001) were predictors of ESBL-producing E. coli-induced bacteraemia. CONCLUSIONS: Antibiotic therapy for patients with the above-mentioned risk factors should be selected considering the possibility of ESBL-producing E. coli-induced bacteraemia compared to non-ESBL-producing E. coli-induced bacteraemia. Furthermore, it is important to elucidate whether appropriate modulation of the identified risk factors can potentially mitigate the risk of ESBL-producing E. coli-induced bacteraemia compared to non-ESBL-producing E. coli-induced bacteraemia.

DOI： 10.1016/j.jhin.2023.09.017

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jvacx.2023.100412

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Mucormycosis is a potentially fatal fungal infection, and there is limited information on its precise epidemiology and treatment practices, including the optimal dosage of liposomal amphotericin B. METHODS: A retrospective, multicenter, nationwide analysis of 82 proven and probable cases of mucormycosis was performed. Cases between 2015 and 2022 were collected from 51 hospitals in Japan by hematologists and infectious disease specialists. The study included the epidemiology, treatment details, and association between the dose of liposomal amphotericin B and the outcome. RESULTS: The lungs were the most commonly involved organ (70.7% of cases), and 35.4% of patients had disseminated disease. Rhizopus spp., Cunninghamella spp., and Mucor spp. were the most common organisms. Mortality at 4 weeks was 41.5%. The survivors had a shorter duration of neutropenia (P = .006) and less persistent hyperglycemia (P = .023). The site of infection and species of Mucorales had no detectable effect on survival. Survival did not differ between patients receiving liposomal amphotericin B at 5 mg/kg/d relative to those receiving >5 mg/kg/d (P = .625). Using Cox proportional hazards models and adjusting for confounders, the hazard ratio for the influence of >5 mg/kg/d liposomal amphotericin B on 4-week survival was 0.86 (95% CI, 0.28-2.68; P = .796) compared with 5 mg/kg/d. CONCLUSIONS: This study provides important insights into the precise epidemiology and treatment practices of mucormycosis. Treatment with liposomal amphotericin B at doses higher than 5 mg/kg/d did not improve outcomes relative to 5 mg/kg/d.

DOI： 10.1093/ofid/ofad480

PubMed

International / domestic magazine：International journal  

Blastomycosis is a fungal infectious disease that can occur in both immunocompromised and immunocompetent populations endemic in North America, with no previous reports in Japan. A 26-year-old Japanese female patient with no relevant medical history presented intermittent left back pain and an abnormal shadow in the left upper lung field eight months ago at a local clinic. She was referred to our hospital for further evaluation and treatment. The patient currently lives in Japan, but until two years ago had spent several years in New York, Vermont and California. Chest computed tomography revealed a 30 mm mass with a cavity in the left pulmonary apex. The specimens obtained by transbronchial biopsy showed periodic acid-Schiff stain (PAS)-positive and Grocott-positive yeast-like fungi scattered among the granulomas, with no malignant findings, and the initial pathology did not lead to a definitive diagnosis. She was empirically started on fluconazole because of onset of multiple subcutaneous abscesses and was referred to the Medical Mycology Research Center. Although antibody tests could not diagnose the disease, blastomycosis was suspected based on the pathology of the skin and lung tissue at the Medical Mycology Research Center, and Blastomyces dermatitidis was identified by ITS analysis of the rRNA region. Her symptoms and CT findings gradually improved with fluconazole. We reported the first Japanese case of blastomycosis with pulmonary and cutaneous involvement in Japan. As the number of overseas travelers is expected to continue increasing, we would like to emphasize the importance of travel history interviews and information of blastomycosis.

DOI： 10.1016/j.jiac.2023.06.004

PubMed

DOI： 10.2169/internalmedicine.1074-22

PubMed

International / domestic magazine：International journal  

Sinusoidal obstruction syndrome (SOS) is a fatal complication after hematopoietic stem cell transplantation (HSCT). Only a few complications after HSCT have been reported as risk factors for SOS, including sepsis. Here, we report the case of a 35-year-old male diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent peripheral blood HSCT from a human leukocyte antigen-matched unrelated female donor in remission. Graft-versus-host disease prophylaxis contained tacrolimus, methotrexate, and low-dose anti-thymoglobulin. The patient was treated with methylprednisolone for engraftment syndrome from day 22. On day 53, he presented worsening fatigue, breathlessness, and abdominal pain in the right upper quadrant that had persisted for 4 days. Laboratory tests showed severe inflammation, liver dysfunction, and positive for Toxoplasma gondii PCR. He died on day 55. An autopsy showed SOS and disseminated toxoplasmosis. Hepatic infection with T. gondii was identified in zone 3 of the liver, which overlapped with the pathological features of SOS. In addition, the timing of the exacerbation of hepatic dysfunction coincided with the onset of systemic inflammatory symptoms and T. gondii reactivation. This rare case of toxoplasmosis is the first to suggest that hepatic infection with T. gondii is strongly associated with SOS after HSCT.

DOI： 10.1016/j.jiac.2023.05.009

PubMed

DOI： 10.1016/j.jiac.2023.04.008

PubMed

<p><b>Objective </b>Third-generation cephalosporins (3GCs) may be susceptible <i>in vitro</i> to <i>Enterobacter</i> spp. and <i>Klebsiella aerogenes</i>. However, treatment with mainly fourth-generation cephalosporins or carbapenems is currently recommended. Diversification of antimicrobial agents in therapy is required to avoid the selection pressure of resistant organisms by broad-spectrum antimicrobial agents. This study investigated the clinical efficacy of 3GC therapy for <i>Enterobacter</i> spp. and <i>Klebsiella aerogenes</i> bacteremia in a multicenter, retrospective, observational study. </p><p><b>Methods </b>Patients with <i>Enterobacter</i> spp. or <i>Klebsiella aerogenes</i> detected in blood cultures and treated with a susceptible antimicrobial agent were included in the study. Propensity score matching was performed to align patient background bases, and clinical outcomes between the 3GC and non-3GC groups were compared. Treatment success was defined as having no need for treatment escalation or the addition of other antimicrobial agents, no recurrence, or no death within 30 days. </p><p><b>Results </b>The study included 188 cases, of which 57 and 131 were included in the 3GC and non-3GC treatment groups, respectively; 53 patients in each group were matched by propensity score matching. There were no significant differences between groups in rates of switching to a susceptible antimicrobial or adding another agent, relapse within 30 days, or death within 30 days. In the 3GC group, source control was associated with favorable clinical outcomes. </p><p><b>Conclusion </b>Definitive 3GC therapy for susceptible <i>Enterobacter</i> spp. and <i>Klebsiella aerogenes</i> bacteremia is as clinically effective and valuable a targeted therapy as non-3GC therapy and can be implemented under conditions in which infection source control measures are in place. </p>

DOI： 10.2169/internalmedicine.0612-22

PubMed

2010年1月～2020年12月に日本の2施設において血液培養でEnterobacter属またはKlebsiella aerogenesが検出され、感受性抗菌薬治療を行った成人患者188例を対象に後向き観察研究を行い、第3世代セファロスポリン系薬(3GC)の臨床的有効性を評価した。57例が3GC治療を行った。傾向スコアマッチング後、3GC群53例、非3GC群53例を抽出した。治療成功の定義は、治療増強または他の抗菌薬追加の必要性なし、30日以内の再発なし、30日以内の死亡なしの場合とした。3GC群と非3GC群で、感受性抗菌薬の変更率/他剤の追加率(9.4 vs 5.7%)、30日以内の再発率(7.5 vs 5.7%)、30日以内の死亡率(3.8 vs 11.3%)に有意差は認めなかった。3GC群において、感染源コントロールは良好な臨床アウトカムと関連した。Enterobacter属およびK.aerogenes菌血症に対する根治的3GC療法は臨床的に有効であることが示された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

BACKGROUND: Healthcare workers (HCWs) caring for patients with coronavirus disease-2019 (COVID-19) can experience physical and mental health burdens. It is imperative that hospitals reduce such burdens on frontline HCWs, protect them, and support their healthcare. This study aimed to investigate the association between occupation and the manifestation of physical or psychological symptoms among HCWs during the current COVID-19 pandemic. METHODS: A twice-weekly survey using questionnaires targeting HCWs who care for COVID-19 patients was performed at Osaka Metropolitan University Hospital (tertiary hospital). The demographic characteristics of the participants, exposure level, and physical and psychological complaints were evaluated. RESULTS: Seventy-one HCWs participated in this study, of whom 27 (38.0%) were doctors, 25 (35.2%) were nurses, and 19 (26.8%) were technicians. Among the HCWs, the proportions of those who experienced any physical or psychological symptoms were 28.2% and 31.0%, respectively. The frequency of depression and anxiety was obviously higher among the nurses than that among the doctors (both p < 0.01). Multivariate analysis revealed that being a nurse (odds ratio 4.90; p = 0.04) and having physical complaints (odds ratio 4.66; p = 0.02) might be independent predictors of the manifestation of psychological symptoms. CONCLUSION: Our results indicate that the follow-up of HCWs experiencing physical symptoms, especially nurses engaged in the care of COVID-19 patients, may require more careful management to improve the psychological outcomes. We believe that this study is the first step toward establishing a psychological health management strategy for HCWs caring for COVID-19 patients.

DOI： 10.1002/jgf2.632

PubMed

DOI： 10.1016/j.jiac.2023.03.021

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Nelfinavir, an orally administered inhibitor of human immunodeficiency virus protease, inhibits the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. We conducted a randomized controlled trial to evaluate the clinical efficacy and safety of nelfinavir in patients with SARS-CoV-2 infection. We included unvaccinated asymptomatic or mildly symptomatic adult patients who tested positive for SARS-CoV-2 infection within 3 days before enrollment. The patients were randomly assigned (1:1) to receive oral nelfinavir (750 mg; thrice daily for 14 days) combined with standard-of-care or standard-of-care alone. The primary endpoint was the time to viral clearance, confirmed using quantitative reverse-transcription PCR by assessors blinded to the assigned treatment. A total of 123 patients (63 in the nelfinavir group and 60 in the control group) were included. The median time to viral clearance was 8.0 (95% confidence interval [CI], 7.0 to 12.0) days in the nelfinavir group and 8.0 (95% CI, 7.0 to 10.0) days in the control group, with no significant difference between the treatment groups (hazard ratio, 0.815; 95% CI, 0.563 to 1.182; P = 0.1870). Adverse events were reported in 47 (74.6%) and 20 (33.3%) patients in the nelfinavir and control groups, respectively. The most common adverse event in the nelfinavir group was diarrhea (49.2%). Nelfinavir did not reduce the time to viral clearance in this setting. Our findings indicate that nelfinavir should not be recommended in asymptomatic or mildly symptomatic patients infected with SARS-CoV-2. The study is registered with the Japan Registry of Clinical Trials (jRCT2071200023). IMPORTANCE The anti-HIV drug nelfinavir suppresses the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro. However, its efficacy in patients with COVID-19 has not been studied. We conducted a multicenter, randomized controlled trial to evaluate the efficacy and safety of orally administered nelfinavir in patients with asymptomatic or mildly symptomatic COVID-19. Compared to standard-of-care alone, nelfinavir (750 mg, thrice daily) did not reduce the time to viral clearance, viral load, or the time to resolution of symptoms. More patients had adverse events in the nelfinavir group than in the control group (74.6% [47/63 patients] versus 33.3% [20/60 patients]). Our clinical study provides evidence that nelfinavir, despite its antiviral effects on SARS-CoV-2 in vitro, should not be recommended for the treatment of patients with COVID-19 having no or mild symptoms.

DOI： 10.1128/spectrum.04311-22

PubMed

DOI： 10.1016/j.jiac.2023.02.001

PubMed

侵襲型肺アスペルギルス症は新型コロナウイルス感染症(COVID-19)の重要な合併症なので、COVID-19患者から単離したAspergillus属の種の株、感受性、遺伝的均一性を分析した。2020年12月～2021年6月に当院に入院したCOVID-19患者から検出されたAspergillus属の株を薬物感受性試験とTRESPERGタイピングにより検索した。COVID-19患者122名のうち11名に12株のAspergillus属が検出された。A.fumigatusが最も多く、A.aureolus、A.nidulans、A.niger、A.terreusが各1株ずつ検出された。A.aureolusはボリコナゾール抵抗性であったが、他の株に薬物抵抗性は認められなかった。11名のうち6名が抗真菌薬治療を受けており、β-D-グルカンおよび/またはAspergillusガラクトマンナン抗原試験が陽性であった。この結果は、Aspergillus感染が病院外感染であることを示していた。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Klebsiella pneumoniae strains pose a significant threat to public health. Currently, it is inconclusive whether hypermucoviscous K. pneumoniae (hmKp; semi-quantitatively defined by a positive 'string test') bacteraemia is clinically more severe than non-hmKp bacteraemia. Hence, this systematic review and meta-analysis was conducted with the aim of drawing some conclusions on hypermucoviscosity and bacteraemia. METHODS: PubMed and Web of Science databases were searched for all relevant publications from January 2000 to March 2022. The outcome measures were mortality rate and abscess formation. RESULTS: Fourteen observational studies were included in this systematic review, comprising a total of 3092 patients with K. pneumoniae bacteraemia, including 746 (24.1%) patients with hmKp strains. The meta-analysis showed that hmKp bacteraemia did not account for a significant increase in the incidence of all-cause mortality compared with non-hmKp bacteraemia [pooled hazard ratio 1.30, 95% confidence interval (CI) 0.79-2.12; P=0.30]. However, hmKp bacteraemia was associated with a significant increase in the incidence of abscess formation compared with non-hmKp bacteraemia (pooled odds ratio 7.74, 95% CI 4.96-12.06; P<0.00001). CONCLUSIONS: Although mortality may not be dependent on the causative agent, this review reaffirms the importance of the string test to detect hmKp. There is a need for prudent management, especially for patients with hmKp, that should include investigations for liver abscess and/or metastatic spread, and measures for early and proper source control as this can improve the prognosis.

DOI： 10.1016/j.ijantimicag.2023.106767

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKp) infections confer notable morbidity and mortality. Differential diagnosis to determine whether the infections are caused by either the hvKp or classical K. pneumoniae (cKp) strain is particularly important for undertaking optimal clinical care and infection control efforts. AIM: To identify and assess the potential predictors of hvKp infections. METHODS: PubMed, Web of Science, and Cochrane Library databases were searched for all relevant publications from January 2000 to March 2022. The search terms included a combination of the following terms: (i) Klebsiella pneumoniae or K. pneumoniae and (ii) hypervirulent or hypervirulence. A meta-analysis of factors for which risk ratio was reported in three or more studies was conducted, and at least one statistically significant association was identified. FINDINGS: In this systematic review of 11 observational studies, a total of 1392 patients with K. pneumoniae infection and 596 (42.8%) with hvKp strains were evaluated. In the meta-analysis, diabetes mellitus and liver abscess (pooled risk ratio: 2.61 (95% confidence interval: 1.79-3.80) and 9.04 (2.58-31.72), respectively; all P < 0.001) were predictors of hvKp infections. CONCLUSION: For patients with a history of the abovementioned predictors, prudent management, including the search for multiple sites of infection and/or metastatic spread and the enforcement of an early and appropriate source control procedure, should be initiated in consideration of the potential presence of hvKp. We believe that this research highlights the urgent need for increasing clinical awareness of the management of hvKp infections.

DOI： 10.1016/j.jhin.2023.02.005

PubMed

DOI： 10.1016/j.transproceed.2023.02.028

PubMed

DOI： 10.1016/j.jiac.2022.12.014

PubMed

International / domestic magazine：International journal  

Clostridium ramosum is one of the obligate anaerobes that constitute the intestinal flora, and one of the rare Clostridia. With Clostridium ramosum, very few data have been reported to investigate antimicrobial susceptibility for clinical isolates that have caused bacteremia. Here, we report two cases of Clostridium ramosum bacteremia. The first case was a 54-year-old Japanese man with taking 20mg hydrocortisone for hypopituitarism. He presented to the emergency department for an unknown cause cardiopulmonary arrest. At the hospital day 36, he had fever and a drop in blood pressure. Abdomen computed tomography (CT) revealed free air around the ascending colon, we diagnosed with intestinal perforation, and peritonitis. Blood culture revealed Clostridium ramosum. We administered conservative management by 6-week of antibiotic treatment. The second case was a 78-year-old Japanese man with no significant medical history. He was referred to our hospital with fever and abdominal pain. Abdomen CT revealed perforated appendicitis, and blood cultures revealed Clostridium ramosum. We performed emergency surgery, and administered one-week course of antibiotic treatment. This report demonstrates two cases of Clostridium ramosum bacteremia with intestinal perforation, and the antimicrobial susceptibility of each clinical strain. For the future, it is necessary to accumulate data on the susceptibility of clinical isolates in order to find an appropriate treatment.

DOI： 10.1016/j.anaerobe.2023.102695

PubMed

症例は70歳男性で、2型糖尿病と糖尿病性網膜症の基礎疾患があった。左手の小指を車のドアにはさんで爪がはがれてから1ヵ月後、左手の指を動かすのが困難であることに気づいた。かかりつけの整形外科医でステロイド局所注入を受けたが症状は悪化していった。左手の指が拘縮し、親指～薬指が曲がった位置で固定したため当院を紹介された。左手と前腕部のMRI検査で掌の手根管～屈筋腱のT2強調画像に高信号が認められ、浅指屈筋と深指屈筋の腱鞘滑膜炎と滑膜炎が示唆された。滑膜周囲の関節液を吸引し培養した結果、Mycobacterium属菌が検出された。続いて手根管開放術と浅指屈筋・深指屈筋滑膜切除を実施した。切除された滑膜からもMycobacterium属菌が分離された。rpoB遺伝子とhap65遺伝子のシーケンス解析を行った。その結果、滑液と滑膜から分離された菌はM.virginienseと同定された。BLAST検索でM.virginienseのrpoB遺伝子塩基配列と100%、hsp65遺伝子配列と99.3%の類似性を示した。微量液体希釈法による薬剤感受性試験結果とこれまでの報告に基づいて、手術後にエタンブトール、リファブチン、クラリスロマイシンの併用療法を開始した。治療は継続中で左手の指の拘縮と運動の困難さが緩和されつつあった。治療期間は9ヵ月～1年、場合によっては18ヵ月が必要と推測された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Cross-neutralizing capacity of antibodies against SARS-CoV-2 variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2-, 6-, or 10-months post-recovery, and BNT162b2 vaccine recipients at 3- or 25-weeks post-vaccination, were analyzed. Anti-spike IgG avidity was measured on urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescence, avidity indices of late-convalescent sera were significantly higher (median 37.7 (interquartile range 28.4-45.1) vs. 64.9 (57.5-71.5), p < 0.0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman's r = 0.49 vs. 0.67 (wild-type); 0.18-0.52 vs. 0.48-0.83 (variants)). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (p < 0.001 (Alpha); p < 0.01 (Delta and Omicron)). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week-25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the two building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

DOI： 10.1093/infdis/jiac492

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: In hypervirulent Klebsiella pneumoniae (hvKP), the hypermucoviscous capsule is known to be a major virulence determinant. We previously discovered that rifampicin (RFP), a bactericidal drug that binds to and inhibits the β subunit of RNA polymerase (RpoB), elicits anti-mucoviscous activity against hvKP by suppressing rmpA, a regulator of capsule production. Here, we aimed to determine whether RFP exerts this effect at sub-growth-inhibitory concentrations via its binding to RpoB. METHODS: Five spontaneous RFP-resistant mutants (R1-R5) were prepared from an hvKP clinical isolate and subjected to whole genome sequencing and mucoviscosity analyses. Subsequently, a two-step allelic exchange procedure was used to create a rpoB mutant R6 and revertants with wild-type rpoB from R1-R5 (named R1'-R5'). Transcription levels of rmpA and the capsular polysaccharide polymerase gene magA and capsule thickness of R1-R5 and R1'-R5' grown without or with RFP were evaluated by quantitative reverse transcription polymerase chain reaction and microscopic observation using India ink staining. RESULTS: R1-R5 all had non-synonymous point mutations in rpoB and were highly resistant to the bactericidal effects and anti-mucoviscous activity of RFP. While the properties of R6 were similar to those of R1-R5, the responses of R1'-R5' to RFP were identical to those of the wild type. rmpA and magA transcription levels and capsule thickness correlated well with the mucoviscosity levels. CONCLUSIONS: RFP exerts anti-mucoviscous activity by binding to RpoB. The mechanism of how this causes rmpA suppression remains to be explored.

DOI： 10.1016/j.jgar.2022.11.018

PubMed

DOI： 10.1016/j.resinv.2022.12.011

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses. PATIENTS AND METHODS: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT). RESULTS: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole. CONCLUSIONS: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated.

DOI： 10.1016/j.jiac.2022.10.010

PubMed

International / domestic magazine：International journal  

Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) is being increasingly recognized as a severe complication that contributes to poor prognoses among patients with COVID-19. However, little is known regarding the clinical course of CAPA with hematological malignancies, especially after allogeneic hematopoietic stem cell transplantation (HSCT). A 29-year-old woman was diagnosed with proven CAPA with an Aspergillus fumigatus identified by cultures of bronchoalveolar lavage and lung biopsy four years after haploidentical HSCT for acute myelogenous leukemia. She had been taking oral prednisolone for bronchiolitis obliterans syndrome that developed after HSCT. Although prolonged RT-PCR positivity for SARS-CoV-2 (133 days after the onset of COVID-19) without shedding of viable virus was observed, the COVID-19 was treated with favipiravir, remdesivir, dexamethasone, and enoxaparin. However, the CAPA did not respond to combination therapy, which included triazole (voriconazole, itraconazole, posaconazole) and echinocandin (caspofungin, micafungin), even though the Aspergillus fumigatus isolate was found to be susceptible to these agents in vitro. Nevertheless, a total of 16 weeks of liposomal amphotericin B (L-AMB) therapy led to a favorable response, and the patient was discharged from the hospital on day 213. This case provided essential experience of CAPA treated with L-AMB in a recipient with chronic respiratory disease after HSCT.

DOI： 10.1016/j.jiac.2022.10.020

PubMed

2018年4月～2021年4月に日本の39施設において深在性真菌症の日本人患者を対象に、トリアゾール系抗真菌剤イサブコナゾール(ISCZ)の有効性と安全性について検討する第3相無作為化非盲検試験を実施した。アスペルギルス症(慢性肺アスペルギルス症および侵襲性アスペルギルス症)患者をISCZまたはボリコナゾール(VRCZ)に2:1の割合で無作為化し(コホートA)、またはクリプトコッカス症およびムコール症患者をISCZによる最大84日間の治療に割り当てた(コホートB)。その結果、合計103例が登録され、試験薬を投与された。慢性肺アスペルギルス症患者における治療終了時の全奏効率はISCZ群52例(年齢35～86歳)、VRCZ群27例(年齢41～88歳)でそれぞれ82.7%、77.8%であった。クリプトコッカス症患者(10例、ISCZ群のみ)の奏効率は90.0%であった。ISCZ群の侵襲性アスペルギルス症3例中1例、ムコール症3例中1例に奏効が認められた。安全性評価では、慢性肺アスペルギルス症患者における有害事象の発生率は両試験薬群で同等であった。有害事象はISCZ群32例(61.5%)、VRCZ群23例(85.2%)で報告された。以上より、ISCZは慢性肺アスペルギルス症およびクリプトコッカス症の日本人患者において有効性および安全性を示した。

症例は29歳女性で、発熱、息切れ、持続性の乾性咳嗽で当科を受診した。SARS-CoV-2の抗原検査が陽性であり、胸部CTで両側のすりガラス陰影が認められたことから、COVID-19治療のために隔離病棟に入院した。4年前に急性骨髄性白血病の治療で父親からHLA半合致同種造血幹細胞移植を受けていた。白血病は完全寛解に至ったが、造血幹細胞移植から1年半後に閉塞性細気管支炎症候群を発症したため、プレドニゾロンを内服していた。入院後、生存ウイルスの排出を伴わないSARS-CoV-2のRT-PCR陽性の遷延(COVID-19発症後133日)が認められたが、COVID-19をファビピラビル、レムデシビル、デキサメタゾン、エノキサパリンで治療した。しかし、呼吸状態が悪化し、7日目の胸部CTで中心部まで広がるすりガラス陰影と両肺に厚い空洞が多数出現した。気管支肺胞洗浄の培養と肺生検により新型コロナウイルス感染症関連肺アスペルギルス症と診断した。トリアゾール系薬剤(ボリコナゾール、イトラコナゾール、ポサコナゾール)とエキノカンジン系薬剤(カスポファンギン、ミカファンギン)の併用療法には反応しなかったが、合計16週間のリポソーム型アムホテリシンB療法により良好な反応が得られ、213日目に退院した。

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult. Based on the findings of a biopsy of the biceps femoris, which confirmed small vessel vasculitis, the patient was diagnosed with MPA. The fever was alleviated by glucocorticoids. Tuberculosis and antituberculosis drugs can cause ANCA-associated vasculitis (AAV). A muscle biopsy is useful for the diagnosis of AAV. </p>

DOI： 10.2169/internalmedicine.9599-22

PubMed

DOI： 10.1002/ams2.868

PubMed

症例は70歳男性で、他院で行った胸部CTで右上葉の肺結核が示唆された。無症状であったが、喀痰培養でMycobacterium tuberculosisが陽性で、肺結核と診断された。抗結核治療(イソニアジド、リファンピシン、エタンブトール、ピラジナミド)を開始した。その結果、3ヵ月後に持続熱が出現した。薬剤中止後も発熱が持続したため、精査目的で紹介来院した。ミエロペルオキシダーゼ抗好中球細胞質抗体(MPO-ANCA)が陽性で、薬剤誘発性リンパ球刺激試験はイソニアジド陽性であった。胸部CTで間質性肺炎を示唆する所見はみられなかった。造影腹部CT検査およびMRI検査では、発熱の原因となる所見はなかった。経胸壁心エコー検査で疣贅は認めず、血液・喀痰・尿の培養は陰性であった。大腿痛を認め、四肢MRI検査で両側大腿筋の血管炎が示唆された。MPO-ANCA陽性から、顕微鏡的多発血管炎(MPA)が疑われた。右大腿二頭筋の生検を行い、MPAと診断した。MPAをきたす可能性のある薬剤を使用していたことから、薬剤性MPAと診断した。プレドニゾロン投与を開始すると、発熱と大腿痛が速やかに改善した。

DOI： 10.11534/jsmm.64.suppl1.0_60_1

DOI： 10.11534/jsmm.64.suppl1.0_78

DOI： 10.11534/jsmm.64.suppl1.0_50_2

DOI： 10.11534/jsmm.64.suppl1.0_87

Pulmonary aspergillosis is a refractory infectious disease that occurs in patients with impaired immunity or pulmonary underlying diseases. It is roughly categorized into invasive pulmonary aspergillosis and chronic pulmonary aspergillosis depending on their clinical course or underlying diseases. Diagnosing aspergillosis requires a review of background information or radiological findings. As the sensitivity of fungal culture is low, bronchoscopy must be performed to obtain specimen from the site of infection for fungal culture or pathological examination. However, bronchoscopy is occasionally avoided if the patient has poor general conditions. Hence, a better supportive diagnostic method is needed. Galactomannan antigen has good accuracy for the diagnosis of invasive pulmonary aspergillosis, but not for chronic pulmonary aspergillosis. Although the <i>Aspergillus</i> precipitating antibody test has a relatively good sensitivity and specificity for the diagnosis of chronic pulmonary aspergillosis, it is not covered by the Japanese medical insurance system. Approval of <i>Aspergillus</i> IgG EIA antibody tests or the development of new diagnostic methods for pulmonary aspergillosis is necessary.

DOI： 10.11534/ishinkin.23.003

The Japanese Society of Medical Mycoses (JSMM) has issued guidelines regarding the diagnosis and management of candidiasis, aspergillosis, and cryptococcosis in 2013, 2015, and 2019, respectively, and published the updated guidelines for the management and diagnosis of candidiasis in 2021. JSMM is presently preparing new guidelines for the diagnosis and management of rare fungal infections, including mucormycosis, trichosporonosis, fusariosis, scedosporonosis, imported mycoses (histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, and penicilliosis), candidiasis caused by <i>Candida auris</i>, and endogenous endophthalmitis resulting from mold infections. To obtain new evidence, a working group has attempted to conduct a systematic literature review pertaining to six clinical questions (CQs).

DOI： 10.11534/ishinkin.23.004

There is limited evidence available for the diagnosis and management of rare fungal infections including mucormycosis, fusariosis, trichosporonosis, and scedosporiosis. To prepare the JSMM guidelines for the diagnosis and management of rare fungal infections, JSMM organized a Systematic Review Working Group (WG) consisting of eight members (the launching meeting was held on July 20, 2021). WG members came up with ideas on clinical questions (CQs) for systematic review. From among those ideas, a total of six CQs were selected. They include two CQs regarding mucormycosis (optimal duration of treatment, usefulness of combination antifungal therapy), and one each regarding fusariosis (monotherapy or combination therapy as initial therapy), trichosporonosis (azole or polyene antifungal agent as initial therapy), scedosporonosis (optimal initial therapy), and endogenous endophthalmitis due to mold infection (optimal initial therapy). Using a search formula, the WG conducted systematic literature review for each CQ. The progress of the systematic review was reported by the WG in the 66th Annual Meeting of JSMM held in October 2022. In March 2023, a preliminary draft on the recommendations for CQs based on the results of the systematic review was proposed and is now being discussed in the WG. This article provides a report on the progress of the Systematic Review WG activities, from the setting of CQs to the systematic review.

DOI： 10.11534/ishinkin.23.007

Publishing type：Research paper (scientific journal)  

Abstract

Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.

DOI： 10.1038/s41598-022-25398-6

PubMed

Other URL： https://www.nature.com/articles/s41598-022-25398-6

DOI： 10.1186/s12916-022-02695-5

PubMed

2013年1月から2021年7月までに大阪市立大学医学部附属病院(現:大阪公立大学医学部附属病院)において血液培養から検出されたClostridium属およびClostridioides属40株を対象とし,各種同定法による同定成績とGram variabilityによる血液培養陽性時の鏡検結果への影響,そして薬剤感受性試験について検討を行った.検出菌の内訳はC.perfringensが最も多く,次いでC.butyricumであった.16S rRNA解析による同定結果との一致率は,同定キットを用いた場合は属レベルで100%,種レベルで76.7%,MALDI-TOF MSを用いた場合は種レベルで100%の一致であった.Gram variabilityにより血液培養陽性時にグラム陰性桿菌と報告した例は12.5%(5/40株)であり,内訳はC.ramosumが2株,C.tertiumが2株,C.clostridioformeが1株であった.薬剤感受性についてはペニシリン系薬およびカルバペネム系薬に対しては低いMICを示したが,VCMに高いMICを示す菌株も複数存在し,より適切な抗菌薬治療を選択するためにも早期の正確な菌種同定に加え,薬剤感受性の評価も重要であると考える.(著者抄録)

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.mimet.2022.106566

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: In vitro drug screening studies have indicated that camostat mesilate (FOY-305) may prevent SARS-CoV-2 infection into human airway epithelial cells. This study was conducted to investigate whether camostat mesilate is an effective treatment for SARS-CoV-2 infection (COVID-19). METHODS: This was a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Patients were enrolled if they were admitted to a hospital within 5 days of onset of COVID-19 symptoms or within 5 days of a positive test for asymptomatic patients. Severe cases (e.g., those requiring oxygenation/ventilation) were excluded. Patients were enrolled, randomized, and allocated to each group using an interactive web response system. Randomization was performed using a minimization method with the factors medical institution, age, and underlying diseases (chronic respiratory disease, chronic kidney disease, diabetes mellitus, hypertension, cardiovascular diseases, and obesity). The patients, investigators/subinvestigators, study coordinators, and other study personnel were blinded throughout the study. Patients were administered camostat mesilate (600 mg qid; four to eight times higher than the clinical doses in Japan) or placebo for up to 14 days. The primary efficacy endpoint was the time to the first two consecutive negative tests for SARS-CoV-2. RESULTS: One-hundred fifty-five patients were randomized to receive camostat mesilate (n = 78) or placebo (n = 77). The median time to the first test was 11.0 days (95% confidence interval [CI]: 9.0-12.0) in the camostat mesilate group and 11.0 days (95% CI: 10.0-13.0) in the placebo group. Conversion to negative viral status by day 14 was observed in 45 of 74 patients (60.8%) in the camostat mesilate group and 47 of 74 patients (63.5%) in the placebo group. The primary (Bayesian) and secondary (frequentist) analyses found no significant differences in the primary endpoint between the two groups. No additional safety concerns beyond those already known for camostat mesilate were identified. CONCLUSIONS: Camostat mesilate did not substantially reduce the time to viral clearance, based on upper airway viral loads, compared with placebo for treating patients with mild to moderate SARS-CoV-2 infection with or without symptoms. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04657497. Japan Registry for Clinical Trials, jRCT2031200198.

DOI： 10.1186/s12916-022-02518-7

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Although several assays are used to measure anti-receptor-binding domain (RBD) antibodies induced after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination, the assays are not fully comparable in practice. This study evaluated the immunogenicity of the BNT162b2 mRNA vaccine in healthy adults using two immunoassays. METHODS: This prospective cohort study included SARS-CoV-2-naïve adults, predominantly healthcare workers, aged 20-64 years, who received two BNT162b2 vaccine doses between March and May 2021. Blood samples were collected before the first vaccination (S0), before the second vaccination (S1), 4 weeks after the second vaccination (S2), and 6 months after the second vaccination (S3). anti-RBD antibodies were measured using the Architect SARS-CoV-2 IgG II Quant (Abbott Laboratory) and Elecsys anti-SARS-CoV-2 S (Roche Diagnostics) assays. RESULTS: Among the 385 participants, the geometric mean antibody titers (GMTs) on the Architect assay (AU/mL) were 7.5, 693, 7007, and 1030 for S0, S1, S2, and S3, respectively. The corresponding GMTs on the Elecsys assay (U/mL) were 0.40, 24, 928, and 659, respectively. The GMT ratio (S3/S2) was 0.15 on the Architect and 0.71 on the Elecsys assay. The correlation between antibody titers measured with the two assays were strong at all time points after vaccination (Spearman's correlation coefficient: 0.74 to 0.86, P < 0.01 for all). GMT was significantly lower in the older age group after vaccination (P < 0.01), with no significant differences according to sex. Seroprotection (≥5458 AU/mL on the Architect assay and ≥ 753 U/mL on the Elecsys) at each time point was 0 %, 1 %, 67 %, and 1 % on the Architect assay and 0 %, 1 %, 62 %, and 43 % on the Elecsys, respectively. CONCLUSIONS: Two BNT162b2 vaccine doses resulted in adequate anti-RBD antibody response, which varied by age. As the two assays showed different kinetics, the results of single immunoassays should be interpreted with caution.

DOI： 10.1016/j.vaccine.2022.08.018

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: Only a few reports are available on the population pharmacokinetic (PK) analysis of linezolid and its main metabolites. Therefore, we investigated the population PK of linezolid and its metabolites in adult patients treated with intravenous linezolid to identify the causative factors affecting pharmacokinetics, and evaluated the relationship between the parent compound and major metabolites PNU-142300 and PNU-142586. METHODS: Population PK analysis was performed using medical data collected from patients who were treated with intravenous linezolid (600 mg twice daily). We examined the impact of covariate candidates such as demographic characteristics and laboratory parameters. Simulations using the final model were investigated and used to estimate the plasma concentrations, trough concentrations (Cmin ), and area under the curve (AUC) of linezolid and its metabolites, and the metabolite-to-parent ratios for Cmin and AUC were used to assess the accumulation of metabolites over linezolid. RESULTS: A total of 82 plasma concentrations from 23 patients were analyzed. The volume of distribution was estimated to be 47.1 L, assuming that linezolid and its metabolites were the same. The total clearance (CL) of linezolid, and CLs of PNU-142300 and PNU-142586 were influenced by creatinine clearance (CLcr), with population mean CLs of 3.86, 7.27, and 13.54 L/h, respectively. The Cmin and AUCs of linezolid and its metabolites and the ratios of metabolites per linezolid were predicted to increase exponentially with decreasing renal function. CONCLUSION: We developed the first population PK model in which CLcr was incorporated as a covariate in the CL of linezolid and its metabolites. Using the final model, it was possible to predict the plasma concentration, Cmin , and AUC appropriately. The model was found to be a potentially useful tool for future studies on optimal dosing and toxicity analysis.

DOI： 10.1002/phar.2719

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

DOI： 10.1093/qjmed/hcac139

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza. METHODS: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted. RESULTS: Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors. CONCLUSIONS: Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989).

DOI： 10.1016/j.jiac.2022.02.001

PubMed

危険因子を持たない入院中のインフルエンザ患者の臨床所見を明らかにするため、インターネットサーベイランスシステムを介した多施設共同前向き観察研究を実施した。2014年11月から2020年8月(6回のインフルエンザシーズン)に、インフルエンザで重症化し、入院を必要とした患者の臨床データをインターネットサーベイランスシステムで収集・解析し、インフルエンザによる合併症の危険因子がない患者を抽出した。最終的に、危険因子を持たない患者91例(年齢16～64歳)(インフルエンザ関連入院の9.0%)を分析対象とした。危険因子なしの群は危険因子ありの群より若かったが、その他の臨床的特徴に有意差は認められなかった。危険因子なしの群の入院原因は肺炎が最も多く、原発性インフルエンザウイルス肺炎が最も一般的な肺炎であった。抗ウイルス剤投与は危険因子なしの群の96.7%で行われ、人工呼吸は18.7%で行われた。院内死亡は危険因子なしの患者3例で記録された。以上より、入院を必要とするようなインフルエンザの重篤な合併症は、危険因子を持たない患者でも一定程度発生する可能性があった。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan. METHODS: We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality. RESULTS: Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality. CONCLUSION: The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

DOI： 10.1016/j.jgar.2022.04.004

PubMed

<p><b><i>Background.</i></b> A paradoxical reaction is a phenomenon that causes a transient exacerbation of existing lesions or fever after the initiation of tuberculosis treatment, and it is often difficult to differentiate from other diseases. <b><i>Case Presentation.</i></b> A 35-year-old woman with Crohn's disease was referred to our hospital for the evaluation of fever and an abnormal shadow on chest radiography. She was diagnosed with pulmonary tuberculosis and miliary tuberculosis based on a positive sputum smear for acid-fast bacilli; and a positive polymerase chain reaction for <i>Mycobacterium tuberculosis</i>, and treatment with anti-tuberculous drugs was initiated. A negative sputum smear for acid-fast bacilli and the regression of the lesions were confirmed after the initiation of treatment. However, she developed worsening cough 15 months after the initiation of treatment. Furthermore, chest computed tomography revealed enlargement of the mediastinal lymph nodes, enlargement of the consolidation in the right lower lobe, and a bronchial polyp at the truncus intermedius. A sputum smear for acid-fast bacilli was positive. Bronchoscopic biopsy of each lesion was performed, and a histopathological examination revealed caseous necrosis and epithelioid cells; however, no acid-fast bacilli were detected in the biopsy specimens. We continued anti-tuberculosis treatment because we considered that these lesions had formed as a result of a paradoxical reaction. Treatment was discontinued when cultures of bronchoscopic specimens to detect acid-fast bacilli were confirmed to be negative. <b><i>Conclusion.</i></b> Physicians should be aware that paradoxical reactions can occur late in the course of treatment and may have multiple manifestations, and a histological diagnosis should be performed to exclude other diseases.</p>

DOI： 10.18907/jjsre.44.3_199

COVID-19患者の入院が三次医療施設の感染症治療と感染対策に及ぼす影響を調べた。COVID-19患者の入院前(2019年度)と後(2020年度)の期間に分け、救急科と他の診療科の患者数、使用された手指消毒剤の量、血液培養で検出された細菌、シュードモナス属細菌の薬剤耐性、使用された抗菌薬の量を比較した。救急科と他の診療科の、2020年度の入院患者数は2019年度より少なかった。2020年度に救急科、ICU、全病棟で使用された手指消毒剤の量は増加した。2015～2019年度に血液培養で検出された黄色ブドウ球菌のうちメチシリン耐性黄色ブドウ球菌のベースライン検出割合は22.2%、大腸菌と肺炎桿菌のうち基質特異性拡張型βラクタマーゼの割合は25.5%と12.1%であった。2015～2019年度に22件のカルバペネム耐性腸内細菌科細菌が検出されたが、それらのうちカルバペネマーゼ産生菌はなかった。全ての診療科で2019年度と比べて2020年度のメチシリン感受性黄色ブドウ球菌と黄色ブドウ球菌菌血症は有意に減少した。2020年度に救急科以外の診療科でシュードモナス属細菌菌血症患者数が増加したが薬剤感受性に変化は見られなかった。救急科と他の診療科で使用された抗菌薬は増加傾向を示した。COVID-19患者受入れ後入院患者が減少したにもかかわらず手指消毒剤の使用量は増加した。しかし、薬剤耐性菌検出と使用抗菌薬量に明らかな変化は見られなかった。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has greatly impacted medical care practices. Although the effects on infectious disease treatment and infection control, such as antimicrobial resistance, have been specified, very few reports exist on the specific effects of COVID-19. METHODS: We investigated the effects of COVID-19 on daily medical practices at a tertiary hospital in Japan by comparing the use of hand sanitizers, the detection of bacteria from blood cultures, and the amount dose of antibacterial drugs used for one year before (April 2019 to March 2020, fiscal year 2019.) and after COVID-19 admissions began (April 2020 to March 2021, fiscal year 2020). RESULTS: The use of hand sanitizers increased by 1.4-3 times during the year after COVID-19 admissions began; the incidence of methicillin-susceptible Staphylococcus aureus and all S. aureus detected in blood cultures reduced in all departments. No decrease was observed in the usage of all antibacterial drugs; rather, the usage of all antibacterial drugs tended to increase in all departments. Therefore, no significant change was observed in the detection of drug-resistant bacteria and the trends of antibacterial drug use based on the acceptance of COVID-19 patients. CONCLUSIONS: The prevalence of drug-resistant bacteria and trends of antibacterial drug use remained unchanged despite the increased use of hand sanitizers due to the admission of patients with COVID-19.

DOI： 10.1016/j.jiac.2022.01.008

PubMed

背景.Paradoxical reactionは結核治療開始後に一過性に既存病変の悪化や発熱などを生じる現象であり,しばしば他疾患との鑑別に難渋する.症例.クローン病治療中の35歳女性.発熱と胸部異常陰影精査のため当院を紹介受診した.喀痰抗酸菌塗抹,結核菌群PCRともに陽性であり肺結核および粟粒結核と診断した.結核専門病院で入院治療を行い,退院後は当院で治療を継続し画像所見の改善も認めていた.しかし治療開始15ヵ月後から咳嗽悪化と喀痰抗酸菌塗抹再陽性化を認めたほか,胸部CTで縦隔リンパ節と右下葉コンソリデーションの増大,中間幹のポリープ様病変を認めた.気管支鏡にて各病変の生検を施行したところ乾酪壊死と類上皮細胞を認めたが,抗酸菌は検出されなかった.Paradoxical reactionによる変化と考え結核治療を継続したところ症状は改善し,気管支鏡検体の抗酸菌培養陰性確認をもって治療を終了した.結論.Paradoxical reactionでは遅発性に複数の所見を呈することがあり,他疾患除外のためにできる限り組織学的診断を行うべきである.(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND/PURPOSE: Klebsiella pneumoniae bacteremia-induced sepsis is a clinically important condition with a high mortality rate and various known virulence factors. However, studies on the association of these virulence factors with the occurrence of K. pneumoniae bacteremia-induced sepsis are scarce. We aimed to investigate clinical variables and virulence factors in patients with K. pneumoniae bacteremia-induced sepsis. METHODS: We retrospectively reviewed the medical records of 76 patients with K. pneumoniae bacteremia between January 2012 and July 2017. Patients were divided into sepsis (n = 25) and non-sepsis (n = 51) groups. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. We assessed the distribution of virulence factors related to K. pneumoniae, such as mucoviscosity, capsular polysaccharide, and siderophores. Siderophore production levels were determined by measuring the orange halo zone on chrome azurol S agar plate assay. RESULTS: There were no intergroup differences in male-to-female ratio and age. Multivariable analysis revealed that siderophore production level (p < 0.01) was an independent predictor of K. pneumoniae bacteremia-induced sepsis. Furthermore, the optimal cut-off point of siderophore production to predict sepsis was 9.6 mm (sensitivity, 86%; specificity, 76%; AUC, 0.81). CONCLUSION: Siderophore production was an independent predictor of sepsis caused by K. pneumoniae bacteremia. The optimal cut-off point for siderophore production for sepsis occurrence prediction was 9.6 mm. To improve outcomes, patients with K. pneumoniae bacteremia-induced sepsis with high siderophore production levels should be managed prudently.

DOI： 10.1016/j.jfma.2021.06.027

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

An internet questionnaire survey for investigating empirical antibiotic usage and bacterial superinfections in patients with coronavirus disease-2019 (COVID-19) in Japan was conducted among the chief physicians of respiratory disease departments of 715 Japanese Respiratory Society-certified hospitals using Google Forms between January 28, 2021 and February 28, 2021. Responses to the questionnaire survey were obtained from 198 of 715 hospitals (27.6%). The survey revealed that the complication incidences of community-acquired pneumonia; hospital-acquired pneumonia, including ventilator-associated pneumonia; and sepsis were 2.86, 5.59, and 0.99%, respectively, among patients with moderate/severe and critical COVID-19. Bacterial co-infection and secondary infection rarely affected patients with COVID-19 in Japan, and the isolated pathogens were not specific to these patients. Moreover, the anti-inflammatory effects of macrolides for COVID-19 were not observed in several studies. These results might be useful in clinical practice for COVID-19.

DOI： 10.1016/j.resinv.2021.09.004

PubMed

DOI： 10.11534/jsmm.63.suppl1.0_107_2

DOI： 10.11534/jsmm.63.suppl1.0_104

DOI： 10.11534/jsmm.63.suppl1.0_79_2

DOI： 10.11534/jsmm.63.suppl1.0_77

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

In clinical settings, the number of immune compromised patients have increased as a result of developments in medical technology (e.g., organ transplantation, anticancer drugs, steroids, TNF inhibitors, etc.). However, patients with fungal diseases are also increasing globally. In recent years, the distribution and pathogenicity of fungi worldwide have been changing, with reports that new fungi are emerging, and antifungal-resistant fungi are spreading globally. Global warming, globalization, human activities, and other factors have been suggested as contributing to the emergence of new fungi. Some of the antifungals against which resistant fungi have emerged are commonly used not only for human but also for animal health care and crop protection. Consequently, the occurrence of antifungal-resistant fungi has become a clinical issue. Solving these problems entails continuing the “One Health” approach, which in turn requires updating medical mycology information with regard to the emerging pathogenic fungi. In particular, this paper reviews the recent information on <i>Cryptococcus gattii</i>, <i>Candia auris</i>, and azole-resistant <i>Aspergillus fumigatus</i>.

DOI： 10.3314/mmj.22.001

PubMed

CiNii Article

DOI： 10.11534/jsmm.63.suppl1.0_100_2

DOI： 10.11534/jsmm.63.suppl1.0_110

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. METHODS: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight < 18.5, normal weight 18.5-25.0, and obese ≥ 25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. RESULTS: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (P < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (P < 0.05). CONCLUSION: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient's renal function but also based on BMI.

DOI： 10.1159/000522455

PubMed

International / domestic magazine：International journal  

A 78-year-old Japanese woman without any history of asthma or smoking presented prolonged cough. Laboratory data showed elevated serum CEA levels and a chest CT revealed a mass with abnormal uptake in the left lower lobe. One month later, the mass spontaneously regressed, and CEA levels improved. However, the symptoms progressed during the observation period without treatment. Chest radiograph findings revealed collapse of the right middle lobe, and Schizophyllum commune was isolated from the mucous plugs; the patient was diagnosed with allergic bronchopulmonary mycosis (ABPM). Herein, we report the first case of ABPM caused by S. commune with elevated CEA levels and mimicking lung cancer.

DOI： 10.1016/j.rmcr.2022.101677

PubMed

DOI： 10.11534/jsmm.63.suppl1.0_75_1

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The prompt rollout of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is facilitating population immunity, which is becoming more dominant than natural infection-mediated immunity. In the midst of coronavirus disease 2019 (COVID-19) vaccine deployment, understanding the epitope profiles of vaccine-elicited antibodies will be the first step in assessing the functionality of vaccine-induced immunity. In this study, the high-resolution linear epitope profiles of Pfizer-BioNTech COVID-19 mRNA vaccine recipients and COVID-19 patients were delineated by using microarrays mapped with overlapping peptides of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The vaccine-induced antibodies targeting the RBD had a broader distribution across the RBD than that induced by the natural infection. Half-maximal neutralization titers were measured in vitro by live virus neutralization assays. As a result, relatively lower neutralizability was observed in vaccine recipient sera, when normalized to a total anti-RBD IgG titer. However, mutation panel assays targeting the SARS-CoV-2 variants of concern have shown that the vaccine-induced epitope variety, rich in breadth, may grant resistance against future viral evolutionary escapes, serving as an advantage of vaccine-induced immunity. IMPORTANCE Establishing vaccine-based population immunity has been the key factor in attaining herd protection. Thanks to expedited worldwide research efforts, the potency of mRNA vaccines against the coronavirus disease 2019 (COVID-19) is now incontestable. The next debate is regarding the coverage of SARS-CoV-2 variants. In the midst of vaccine deployment, it is of importance to describe the similarities and differences between the immune responses of COVID-19 vaccine recipients and naturally infected individuals. In this study, we demonstrated that the antibody profiles of vaccine recipients are richer in variety, targeting a key protein of the invading virus, than those of naturally infected individuals. Vaccine-elicited antibodies included more nonneutralizing antibodies than infection-elicited antibodies, and their breadth in antibody variations suggested possible resilience against future SARS-CoV-2 variants. The antibody profile achieved by vaccinations in naive individuals provides important insight into the first step toward vaccine-based population immunity.

DOI： 10.1128/Spectrum.00965-21

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

<title>Abstract</title>
<sec>
<title>Objectives</title>
To characterize Acinetobacter baumannii OCU_Ac16a, a clinical isolate co-harbouring three acquired carbapenemase genes, blaNDM-1, blaTMB-1, and blaOXA-58, and assess the clinical significance of so-called multiple-carbapenemase producers.


</sec>
<sec>
<title>Methods</title>
OCU_Ac16a and its close relative, OCU_Ac16b, which lacks the blaNDM-1, were isolated from sputum cultures of a patient at Osaka City University Hospital. We subjected these strains to whole-genome analysis, particularly focusing on the genetic context of each carbapenemase gene. The transmissibility and functionality of each carbapenemase gene were analysed by conjugation and transformation experiments and antimicrobial susceptibility tests.


</sec>
<sec>
<title>Results</title>
bla TMB-1 was located in a class 1 integron on the chromosome, whereas blaNDM-1 and blaOXA-58 were found on plasmids named pOCU_Ac16a_2 and pOCU_Ac16a_3, respectively. pOCU_Ac16a_2 (which exhibited highly efficient self-transmissibility) and pOCU_Ac16a_3 (which did not show transmissibility but could be introduced into another A. baumannii strain via electroporation) could both confer carbapenem resistance (MICs ≥512 and ≥32 mg/L, respectively) on the recipient strain. The functionality of blaTMB-1 was evident from the high resistance of OCU_Ac16b to ceftazidime and cefepime (MICs ≥256 and 48 mg/L, respectively), and the high resistance of OCU_Ac16a to cefiderocol (MIC 32 mg/L) could be explained by the additive effect of blaNDM-1 and blaTMB-1.


</sec>
<sec>
<title>Conclusions</title>
Our data revealed the genomic organization of OCU_Ac16a and demonstrated that all the carbapenemase genes are functional, each contributing to the extremely high broad-spectrum resistance of OCU_Ac16a to β-lactams. As multiple-carbapenemase producers can be serious health threats as drug-resistant pathogens and disseminators of carbapenemase genes, close attention should be paid to their emergence.


</sec>

DOI： 10.1093/jacamr/dlab191

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Several severity indexes have been reported for critically ill patients. The Pitt bacteremia score (PBS) is commonly used to predict the risk of mortality in patients with bacteraemia. OBJECTIVES: To develop a scoring system for predicting mortality in candidaemia patients. METHODS: Medical records at five Japanese tertiary hospitals were reviewed. Factors associated with mortality were analysed using logistic regression modelling. The discriminatory power of scoring models was evaluated by assessing the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: In total, 422 candidaemia patients were included. Higher PBS, dialysis and retainment of central venous catheter were independent risk factors for all-cause 30-day mortality. However, among the five PBS components, fever was not associated with mortality; therefore, we developed a modified version of the PBS (mPBS) by replacing fever with dialysis. AUC for PBS and mPBS were 0.74 (95% confidence interval [CI]: 0.68-0.80) and 0.76 (95% CI: 0.71-0.82), respectively. The increase in predictive ability of mPBS for 30-day mortality was statistically significant as assessed by NRI (0.24, 95% CI: 0.01-0.46, p = .04) and IRI (0.04, 95% CI: 0.02-0.06, p = .0008). When patients were stratified by mPBS into low (scores 0-3), moderate (4-7) and high risk (≥8), there were significant differences among the survival curves (p < .0001, log-rank test), and 30-day mortality rates were 13.8% (40/290), 36.8% (28/76) and 69.4% (34/49), respectively. CONCLUSIONS: mPBS can be a useful tool for predicting mortality in candidaemia patients.

DOI： 10.1111/myc.13380

PubMed

症例は73歳男性で、食道の粘膜関連リンパ組織リンパ腫と診断され、リツキシマブを8回投与後、局所照射を行った。最終リツキシマブ投与の12週後、発熱と呼吸症状が出現し、SARS-CoV-2陽性が判明した。呼吸検体だけでなく血清もSARS-CoV-2陽性であったことから、SARS-CoV-2播種によるRNA血症が示唆された。胸部CT所見から、新型コロナウイルス感染症(COVID-19)H型が示唆された。重度呼吸障害のために機械的換気を行い、ファビピラビルとクロロキンによる併用療法を行ったが、明らかな有効性は得られなかった。高用量メチルプレドニゾロンにより換気パラメータが軽度に改善したが、一過性であった。イベルメクチン単回投与を行ったが、発症24日目の喀痰PCRは、依然としてSARS-CoV-2陽性であった。発症25日目の血清SARS-CoV-2特異的抗体検査では矛盾した結果が得られ、スパイク標的ウイルス中和抗体は検出レベル未満であったが、抗ヌクレオカプシド結合抗体の程度と動態は他の免疫正常重度COVID-19患者と同等であった。発症29日目、酸素化不良により死亡した。

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>Drug-induced thrombocytopenia occurs through immune-mediated platelet destruction, and its management is challenging during tuberculosis treatment. Although rifampicin is the most common drug causing thrombocytopenia, isoniazid can also cause thrombocytopenia. We herein report a 75-year-old man who developed thrombocytopenia during tuberculosis treatment. Platelet-associated immunoglobulin G and a drug-induced lymphocyte stimulation test for isoniazid were positive; no other causes of thrombocytopenia were identified. The patient was diagnosed with isoniazid-induced immune thrombocytopenia, and the platelet count normalized after isoniazid discontinuation. We describe the immunological mechanism of thrombocytosis due to isoniazid, an uncommon cause of thrombocytopenia that physicians should be aware exists. </p>

DOI： 10.2169/internalmedicine.6520-20

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Introduction: Combined use of vancomycin (VCM) and piperacillin/tazobactam (PIPC/TAZ) has been reported to increase the incidence of acute kidney injury (AKI). However, the risk factors associated with AKI after VCM and PIPC/TAZ (VPT) administration have not yet been identified. Therefore, we retrospectively assessed patients treated with VPT to investigate the risk factors for AKI development. Methods: The study involved patients who were treated with VPT from January 1, 2016 to March 31, 2020. The patients were divided into the AKI or non-AKI group. The clinical characteristics of patients and antimicrobial therapy were compared between the groups. Their association with AKI risk was evaluated using multivariate logistic regression analysis. Results: In total, 182 patients were included, with 118 in the non-AKI group and 64 in the AKI group. Therefore, the incidence of AKI was 35.2 %. The initiation of VPT combination therapy on the same day and concomitant use of vasopressors were associated with an increased risk of AKI (odds ratio [OR] 2.55, 95 % confidential interval [CI] 1.20-5.44 and OR 3.22, 95 % CI 1.31-7.89, respectively). Conclusion: Our findings suggest that the concomitant use of vasopressors and initiating VPT combination therapy on the same day are likely risk factors for AKI development.

DOI： 10.1016/j.jiac.2021.07.017

PubMed

症例は75歳男性で、結核および結核性脊椎炎と診断され、他院でリファンピシン(RFP)、イソニアジド(INH)、エタンブトール(EB)、ピラジナミドによる治療を開始した。1ヵ月後、肝毒性が出現し、薬剤を中止した。薬剤中止後11日目、血小板数が減少し、その後に増加した。肝機能が改善後、INHとRFPで脱感作したが、肝毒性が再発した。RFPを中止し、INHとEBを継続した。治療開始後3ヵ月目(RFP中止後10日目)、治療継続が困難であったため、搬送されてきた。血小板数が少なかったため、入院1日目と2日目に血小板輸血を行った。貧血に対し、入院1日目に赤血球輸血も行った。検査所見から、結核による二次性貧血と診断した。血小板数の減少はINH投与と関連していたため、入院3日目にINHを中止し、レボフロキサシンとストレプトマイシンを追加した。血小板関連免疫グロブリンGが陽性で、薬剤誘発性リンパ球刺激試験ではINHが陽性、RFPが陰性であった。血小板減少の他の原因は特定されなかったため、INH誘発性免疫性血小板減少症と診断した。INHを中止後、血小板数は正常化した。

バンコマイシン(VCM)とピペラシリン/タゾバクタム(PIPC/TAZ)の併用療法(VPT)を受けた患者における急性腎障害(AKI)の発症リスクを後方視的に検討した。2016年1月1日から2020年3月31日までにVPTを実施した患者182例のうち、AKIを発症した患者(AKI群)は64例、発症しなかった患者(非AKI群)は118例であり、AKIの発生率は35.2%であった。VCMまたはPIPC/TAZの開始からVPT併用療法開始までの日数中央値はAKI群で有意に短かった。VPT併用療法は、非AKI群に比べてAKI群で有意に多くの患者で同日に開始された。また、AKI群では、VPT併用療法開始からAKI発症までの期間の中央値は3日(範囲1～14日)であり、30日死亡率は両群間に有意差はなかった。多変量ロジスティック回帰分析により、VPT併用療法の同日開始および血管収縮薬の併用は、AKIのリスク上昇と関連していた(それぞれ、オッズ比2.55、95%CI:1.20～5.44およびオッズ比3.22、95%CI:1.31～7.89)。以上より、VPT併用療法の同日開始と血管収縮薬の併用は、AKI発症の危険因子である可能性が示唆された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Invasive aspergillosis is a significant cause of mortality in patients with hematological malignancy. Early diagnosis of invasive pulmonary aspergillosis (IPA) by bronchoscopy is recommended but is often difficult to perform because of small lesion size and bleeding risk due to thrombocytopenia. A 71-year-old woman had received initial induction therapy for acute myeloid leukemia. On day 22 of chemotherapy, she had a high fever, and the chest computed tomography scan revealed a 20-mm-sized nodule with a halo sign. Bronchoscopy assisted by virtual bronchoscopic navigation (VBN) and endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed, and Aspergillus terreus was identified from the culture of obtained specimens. A. terreus is often resistant to amphotericin B; thus, voriconazole is usually recommended for treatment. However, the obtained A. terreus isolate showed minimal inhibitory concentrations of 2 µg/mL for voriconazole and 0.5 µg/mL for amphotericin B. Therefore, the patient was successfully treated with liposomal amphotericin B. For patients suspected of having IPA, early diagnosis and drug susceptibility testing are very important. This case suggests that bronchoscopy using VBN and EBUS-GS is helpful for accurate diagnosis and successful treatment even if the lesion is small and the patient has a bleeding risk.

DOI： 10.1007/s15010-020-01545-x

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Here, we report the complete genome sequence of an
<named-content content-type="genus-species">Acinetobacter baumannii</named-content>
isolate harboring 11 plasmids, obtained at a hospital in Japan in 2016. The complete 4.07-Mbp genome sequence (1 chromosome and 11 plasmids) was analyzed by a combination of long-read (Flongle) and short-read (NovaSeq 6000) sequencing.

DOI： 10.1128/MRA.00695-21

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

<named-content content-type="genus-species">Acinetobacter pittii</named-content>
isolate OCU_Ac17 was obtained from the venous blood of a patient at a hospital in Japan. We present its complete 4.108-Mbp genome sequence (1 chromosome plus 3 plasmids), analyzed by combining long-read (Flongle) and short-read (MiniSeq) sequencing.

DOI： 10.1128/MRA.00696-21

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Healthcare workers (HCWs) who manage patients with the novel coronavirus disease 2019 (COVID-19) are at an increased risk and fear of contracting the infection themselves. Hospitals must reduce both the physical and mental burden of HCWs on the front lines and ensure their safety. No prospective study has focused on the physical health complaints among HCWs engaged in the care of critically ill COVID-19 patients. This study aimed to evaluate the prevalence of various physical symptoms experienced by HCWs following their exposure to COVID-19 patients and investigate the association between occupation and the manifestation of physical symptoms among HCWs at a tertiary hospital in Japan during the current ongoing COVID-19 pandemic. METHODS: A twice-weekly questionnaire targeting HCWs who care for COVID-19 patients was performed at Osaka City University Hospital from April 30 to May 31, 2020. The demographic characteristics of the participants, frequency of exposure to at-risk care, and physical complaints were evaluated. RESULTS: Seventy-six HCWs participated in this study, of whom 24 (31.6%) were doctors, 43 (56.6%) were nurses, and 9 (11.8%) were technicians. The frequency of experiencing any physical symptom was 25.0% among HCWs. Exposure to at-risk care was significantly higher among nurses than among doctors (p < 0.001). Notably, the frequency of physical symptoms among the nurses was very high at 39.5% and obviously higher than that of physical symptoms among the doctors (p < 0.01). CONCLUSIONS: Our results indicate that hospital occupational health care must be provided to HCWs who are engaged in the care of COVID-19 patients and are thus highly exposed to at-risk care.

DOI： 10.1016/j.jiph.2021.08.023

PubMed

DOI： 10.24479/j01814.2021305794

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The spread of vancomycin-resistant enterococci (VRE) is a major threat in nosocomial settings. A large-scale multiclonal VRE outbreak has rarely been reported in Japan due to low VRE prevalence. We evaluated the transmission of vancomycin resistance in a multiclonal VRE outbreak, conducted biological and genomic analyses of VRE isolates, and assessed the implemented infection control measures. In total, 149 patients harboring VanA-type VRE were identified from April 2017 to October 2019, with 153 vancomycin-resistant Enterococcus faecium isolated being grouped into 31 pulsotypes using pulsed-field gel electrophoresis, wherein six sequence types belonged to clonal complex 17. Epidemic clones varied throughout the outbreak; however, they all carried vanA-plasmids (pIHVA). pIHVA is a linear plasmid, carrying a unique structural Tn1546 containing vanA; it moves between different Enterococcus spp. by genetic rearrangements. VRE infection incidence among patients in the "hot spot" ward correlated with the local VRE colonization prevalence. Local prevalence also correlated with vancomycin usage in the ward. Transmission of a novel transferrable vanA-plasmid among Enterococcus spp. resulted in genomic diversity in VRE in a non-endemic setting. The prevalence of VRE colonization and vancomycin usage at the ward level may serve as VRE cross-transmission indicators in non-intensive care units for outbreak control.

DOI： 10.1038/s41598-021-94213-5

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2021.02.026

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2021.01.005

PubMed

症例は66歳男性で、持続性発熱と腰痛を主訴とした。5年前に大動脈弁狭窄症(AS)と診断されていた。1年前に労作時呼吸困難と倦怠感が観察され、10ヵ月前の心電図検査で重度のASと判明していた。8ヵ月前の冠動脈CTと血管造影検査で右冠動脈狭窄症と左前下行枝狭窄症が判明していた。5ヵ月前に冠動脈バイパスと生体弁による大動脈弁置換術を受けていた。持続性完全房室ブロックのため4ヵ月前までペースメーカーを埋め込んでいた。術後2～3ヵ月後から発熱と腰痛が出現した。受診時のCRP値は高値であった。心雑音、Janeway病変、Osler結節はみられなかった。経食道心エコー図検査で僧帽弁の前尖に2個の疣贅と弁周囲膿瘍が見つかった。MRI検査で第4/5腰椎化膿性椎間板炎が判明した。タゾバクタム/ピペラシリン(TAZ/PIPC)とバンコマイシン(VCM)による経験的治療を開始し、血液培養を行った。化膿性椎間板炎は抗菌薬療法で治療した。血液からCorynebacterium jeikeiumが分離された。入院6日目にBentall処置、弁輪パッチ修復、三尖弁形成を行い、弁周囲膿瘍を摘出した。膿瘍から菌は培養されなかったが、16SリボソームRNAのシーケンス解析でC.jeikeiumシーケンスと相同性が100%一致した。分離菌がペニシリン耐性、VCM感受性のため、VCM静脈内投与を6週間継続後、リネゾリドに変更し、退院した。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

This study aimed to analyze the risk factors for piperacillin-tazobactam (TZP1)-resistant Enterobacter spp. bacteremia. The medical records of 111 patients with Enterobacter spp. bacteremia divided into a TZP-susceptible group (minimum inhibitory concentrations [MICs2] ≤16 μg/mL) and TZP-resistant group (MICs >16 μg/mL) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, and infection site did not differ between the 2 groups. Multivariate analysis revealed that the independent predictor associated with TZP-resistant Enterobacter spp. bacteremia was the previous usage of third-generation cephalosporins (P = 0.036). In conclusion, TZP administration in cases of suspected Enterobacter spp. bacteremia previously treated with third-generation cephalosporin should be cautiously considered.

DOI： 10.1016/j.diagmicrobio.2021.115342

PubMed

International / domestic magazine：International journal  

CAPA (COVID-19 associated pulmonary aspergillosis) is an important complication of COVID-19. It has been reported that the incidence of CAPA is as high as 19%-33% worldwide. However, its onset has not been reported in Japan. A 72-year-old Japanese man was diagnosed with COVID-19 and was transferred to our hospital due to deterioration of respiratory condition. Treatment with remdesivir, dexamethasone (DEXA), and antibiotics was performed under mechanical ventilation. Although the condition improved temporarily, a new shadow appeared in the lung, and Aspergillus fumigatus was cultured from sputum. The patient was clinically diagnosed with CAPA and treated with voriconazole. However, his progress deteriorated and he died. High-risk COVID-19 patients should be tested for Aspergillus to ensure early diagnosis of CAPA.

DOI： 10.1016/j.jiac.2021.02.026

PubMed

International / domestic magazine：International journal  

INTRODUCTION: Corynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis. CASE REPORT: A 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE. CONCLUSION: 16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.

DOI： 10.1016/j.jiac.2021.01.005

PubMed

キャップ依存性エンドヌクレアーゼであるbaloxavir marboxil(以下、baloxavir)とノイラミニダーゼ阻害薬の臨床効果を比較した報告は少ない。本研究では、2019～2020年のインフルエンザ流行期における各種抗インフルエンザ薬投与後のインフルエンザ罹患患者の臨床経過を調査した。インフルエンザの迅速診断キットで陽性の診断を受けた患者に対して質問紙調査が送付され、有効回答の得られたインフルエンザ罹患患者252例(男性120例、女性132例、平均21.8歳)を解析対象とした。baloxavirは10歳未満の患者97例のうち3例(3.1%)に、10歳以上の患者155例のうち19例(12.3%)に投与された。抗インフルエンザ薬が投与された患者の発熱期間の中央値は2～2.5日であり、oseltamivir(94例)、laninamivir(101例)、zanamivir(32例)またはbaloxavir(22例)の抗インフルエンザ薬の違いによる有意な差はなかった。249例中10例(4.0%)で2相性の発熱エピソードが生じたが、2相性の発熱エピソードの発症頻度と抗インフルエンザ薬の選択に有意な差はなかった。各有害事象の発生頻度にも4群間で差はなかった。以上の結果より、baloxavirの投与と早期発熱の緩和および2相性の発熱エピソードの発症頻度には有意な関連性がないことが示された。

症例は62歳男性。前医にてAspergillus fumigatusによる慢性肺アスペルギルス症と診断され,itraconazoleの経口投与にて外来で治療を継続されていた。しかし,胸部X線上,左肺尖部の陰影の増悪および腎機能の悪化を認めたため,当院の感染症内科に紹介受診となった。提出された喀痰より白色の糸状菌が検出され,ITSおよびD1/D2領域のシークエンス解析にてA.fumigatusの類縁種であるAspergillus thermomutatusと同定した。また,薬剤感受性試験にてアゾール系薬に対し高いMIC値を示したため,micafunginの静脈注射へと変更となった。アスペルギルス症における早期の適切な治療の開始には,正確な菌種の同定および薬剤感受性試験の実施が重要である。(著者抄録)

症例は62歳男性。前医にてAspergillus fumigatusによる慢性肺アスペルギルス症と診断され,itraconazoleの経口投与にて外来で治療を継続されていた。しかし,胸部X線上,左肺尖部の陰影の増悪および腎機能の悪化を認めたため,当院の感染症内科に紹介受診となった。提出された喀痰より白色の糸状菌が検出され,ITSおよびD1/D2領域のシークエンス解析にてA.fumigatusの類縁種であるAspergillus thermomutatusと同定した。また,薬剤感受性試験にてアゾール系薬に対し高いMIC値を示したため,micafunginの静脈注射へと変更となった。アスペルギルス症における早期の適切な治療の開始には,正確な菌種の同定および薬剤感受性試験の実施が重要である。(著者抄録)

症例は72歳男性で、脳卒中による発話障害の悪化とよろめき歩行で、他院で脳梗塞と診断された。SARS-CoV-2の抗原検査とLAMP法で陽性となった。高血圧症、心房細動、COPDの病歴があり、入院1年前まで喫煙していた。抗血小板薬注入とデキサメタゾン(DEXA)治療が開始され、セフトリアキソンとアジスロマイシン(AZM)が投与された。呼吸状態が改善しないため8日後に当院へ移送された。胸部CTで両肺野にすりガラス影が認められた。気管挿管し補助呼吸を開始した。セフトリアキソンとDEXAにレムデシビルを追加した。未分画ヘパリン投与を開始した。入院13日目のCTで右下葉に結節影の集合体が出現した。18日目に発熱、臨床検査結果が悪化し、カテーテル関連血流感染が疑われた。バンコマイシンとセフェピム治療を開始し、中心静脈カテーテルを交換した。X線検査で陰影が悪化したため真菌感染症を考えミカファンギンを追加した。19日目のCT検査で右下葉の結節影集合体が塊状陰影となった。右肺の他の部位にも結節が出現して両下葉にコンソリデーションが発生した。Β-Dグルカン濃度が高く喀痰からA.fumigatusが検出されCOVID-19関連肺アスペルギルス症と診断された。ボリコナゾールに変更した。血清ガラクトマンナン抗原陽性となった。呼吸状態は悪化を続け、発作性上室頻拍が頻発し、26日目に死亡した。

新型コロナウイルス感染症(COVID-19)の罹患後に急性呼吸窮迫症候群(ARDS)を発症した際のARDSに対する治療戦略は、医療従事者への二次感染を回避しながら一般的なARDS治療戦略を最適化する必要がある。本研究では、ARDS合併COVID-19罹患患者に対する治療戦略と転帰を後ろ向きに評価した。2020年3月～6月に単一施設におけるPCR検査でCOVID-19陽性を確認後にARDSを合併した男性患者9例(年齢中央値72歳)を対象とした。入院時のPaO2/FiO2比中央値は116であり、sequential organ failure assessmentスコアの中央値は8であった。2例は敗血症性ショックを呈し、血管拡張剤が投与されていた。治療戦略に基づいて、6例で腹臥位療法が行われたが、体外式膜型人工肺を使用した症例はいなかった。5例はARDSから回復し、合併症もなく気管内チューブは抜去された。本研究期間中における病院での致死率は33.3%であった。以上の結果より、本研究で用いたARDSを合併するCOVID-19罹患患者に対する治療戦略を用いることで、日本の他施設や他国における高い致死率と比較した際に許容できる結果を得ることができた。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Stenotrophomonas maltophilia is a pathogen commonly associated with respiratory infection. However, the characteristics of pneumonia caused by S. maltophilia remain unknown. AIM: To evaluate the characteristics of and risk factors for S. maltophilia pneumonia. METHODS: A retrospective evaluation was undertaken of 2002 patients with sputum cultures positive for S. maltophilia between January 2010 and December 2019. Cases were excluded based on clinical information and laboratory results. Included cases were divided into two groups: the S. maltophilia pneumonia group (patients with pneumonia caused by S. maltophilia) and the non-S. maltophilia pneumonia group (patients with pneumonia caused by pathogens other than S. maltophilia). Patient characteristics, clinical data and Sequential Organ Failure Assessment (SOFA) scores were compared between the groups. FINDINGS: Eight and 91 patients were assigned to the S. maltophilia pneumonia and non-S. maltophilia pneumonia groups, respectively. The median age was significantly lower in the S. maltophilia pneumonia group than in the non-S. maltophilia pneumonia group (63.4 vs 73.1 years; P<0.01), and the SOFA score was significantly higher in the S. maltophilia pneumonia group (7.5 vs 3.0; P<0.01). Underlying malignancy and pre-administration of antipseudomonal β-lactams and steroids were confirmed in seven of the eight cases in the S. maltophilia pneumonia group, suggesting an association with immunosuppression. CONCLUSIONS: Pneumonia due to S. maltophilia is a rare occurrence. Treatment for this pathogen should be considered in cases of pneumonia with: (1) predominance of S. maltophilia in sputum cultures; (2) pre-administration of broad-spectrum antibiotics; (3) immunodeficiency; and (4) a high SOFA score.

DOI： 10.1016/j.jhin.2021.01.011

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2020.10.021

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2020.10.001

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

© 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases Introduction: Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. Methods: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. Results: A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67–84), and the patients in the 2015–2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. Conclusions: Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

DOI： 10.1016/j.jiac.2020.10.021

PubMed

International / domestic magazine：International journal  

Syphilis has recently increased in prevalence in Japan. Neurosyphilis is a special pathological condition of syphilis well known to cause cerebral vasculitis and ischemic stroke. Neurosyphilis in the meningovascular stage rarely causes caliber irregularity of the cerebral blood vessels or cerebral hemorrhage. We describe the case of a 49-year-old Japanese man with neurosyphilis. Cerebral hemorrhage, multiple cerebral infarctions, and caliber irregularity of the cerebral blood vessels were observed, the patient underwent surgery for cerebral hemorrhage on the day of admission, all of which were suspected to be caused by syphilis. He was started on an antibacterial treatment of penicillin on the day of admission and was diagnosed with neurosyphilis the following week based on his serum and spinal fluid test results. His condition improved, and he was transferred to another hospital after 4 weeks of treatment consisting of 3 weeks of infusion treatment with benzylpenicillin followed by oral treatment with amoxicillin. To the best of our knowledge, this is a rare case of neurosyphilis in conjunction with cerebral hemorrhage and cerebral infarction. Clinicians should consider syphilis in the differential diagnosis of cerebral hemorrhage and cerebral infarction and test patients for sexually transmitted diseases, in addition to cerebrospinal fluid testing, when cerebral hemorrhage occurs with an unknown cause. This is especially pertinent when patients present with cerebral infarction or caliber irregularity of the cerebral blood vessels.

DOI： 10.1016/j.jiac.2020.10.001

PubMed

インフルエンザに感染した重症患者の臨床状態を明らかにした。インターネット調査システムで、2014年11月～2019年8月の5インフルエンザシーズンに、インフルエンザで重症化し入院を必要とした患者のデータを収集し分析した。患者924名(中央値78歳、67～84歳)を登録し分析した(2015～2016年シーズンは他のシーズンよりも有意に若かった)。入院の原因としては肺炎が最も多く、続いて全身状態不良と呼吸器疾患の悪化であった。抗ウイルス薬が97.0%の患者に投与され、そのうちでペラミビルが最も多かった。院内死亡は44名(4.8%)であった。多変量解析では、老人ホーム入居者と肥満が院内死亡の独立予測因子であった。インフルエンザの合併は特に高齢者で重い負担となっていることが示された。

症例は神経梅毒の49歳男性。道端で意識を失い、救急搬送された。CTとMRIにて脳出血、複数の脳梗塞と脳血管の径の不整が観察されたため、入院した日に脳出血に対する手術を行った。その原因は梅毒によることが疑われた。入院した日にペニシリンによる抗菌薬治療を開始し、血清と髄液試験の結果から次の週に梅毒と診断した。病状が改善したので、ベンジルペニシリンの3週間の注入療法とその後にアモキシシリン経口投与を行い、転院した。

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.diagmicrobio.2021.115342

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2020.08.020

PubMed

Publishing type：Research paper (scientific journal)  

従来、心臓血管外科手術では、手術部位感染予防抗菌薬としてアンピシリン/スルバクタム(ampicillin/sulbactam:以下、ABPC/SBT)が使用されていたが、抗菌薬供給不足により2019年5月1日からクリンダマイシン(clindamycin:以下、CLDM)が使用された。そこで、予防抗菌薬変更前の2019年3〜4月に手術を受けた28例をABPC/SBT群、変更後の同年5〜6月に手術を受けた20例をCLDM群とし、予防抗菌薬変更が及ぼす影響を調査した。手術部位感染発生例数はABPC/SBT群0例、CLDM群1例で、両群間に統計学的な有意差はなかったが、他剤への変更例数はCLDM群で有意に高かった。本検討よりCLDM群は、抗菌スペクトラムに該当しない原因菌による術後感染症が発生したため、CLDMを使用せざるを得ない場合は、これらの菌種による術後感染症の発生に注意する必要がある。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

INTRODUCTION: Clostridioides difficile is an important causative pathogen in antibiotic-associated colitis and nosocomial infections. This study aimed to assess immunochromatographic test results for C. difficile infection and the utility of PCR-based open-reading frame typing (POT) for potentially controlling the intra-ward transmission of C. difficile. METHODS: We conducted a molecular epidemiological analysis using POT to investigate 102 inpatients who tested positive for the C. difficile toxin using immunochromatography in a tertiary-care teaching hospital in Japan between 2016 and 2018; isolates from the patients were obtained and cultured. RESULTS: The number of POT numbers detected in 2016, 2017, and 2018 were 27 (among 34 patients), 20 (among 31 patients), and 28 (among 37 patients), respectively. During this three-year period, there were seven cases whose bacterial strains with the same POT number was identified in the same ward within 6 months. The intra-ward transmission rate was the highest in 2017 (16.1%). Intra-ward transmission was identified at a higher rate in patients whose sample cultures tested toxin-positive than in patients whose sample cultures tested toxin- and glutamate-dehydrogenase-positive via immunochromatography (16% vs. 3%, p < 0.05). CONCLUSIONS: We conclude that the use of immunochromatographic tests for C. difficile diagnosis and epidemiological analyses via POT may be helpful for evaluating intra-ward transmission of C. difficile.

DOI： 10.1016/j.jiac.2020.08.020

PubMed

3年間の病院内におけるClostridioides difficileトキシン陽性患者のPOT法を用いた分子疫学解析を行った。後ろ向き研究には2016～2018年の間にイムノクロマト検査でC.difficileが陽性となった入院患者102例を登録した。糞便を用いたイムノクロマト検査でGDHとトキシンが陽性を示した患者群をTP群、嫌気培養後にトキシン陽性が確認された患者群をTC群とした。2016、2017、2018年のC.difficileトキシン陽性率はそれぞれ1.16、1.09、1.39/10000PDで、POT型検出数は27/34、20/31、28/37例であった。病棟内伝播株を除き、検出頻度が最も高かったPOT型は826-279(7.8%)であった。2016、2017、2018年に同一病棟で6ヵ月以内に同じPOTナンバーの株が検出された患者の割合はそれぞれ0%(0/34)、16.1%(5/31)、5.4%(2/37)であった。2017年に発生した5例中3例は病棟内伝播が疑われ、そのうち2例はバイナリートキシン陽性であった。TP群の32例中5例(16%)は病棟内伝播であったのに対しTC群では70例中2例(3%)のみが病棟内伝播であった。バイナリートキシン陽性患者の病棟内伝播率の方が陰性患者より高い傾向を示した(p=0.09)。頻繁な下痢とバイナリートキシン陽性を示す患者で病棟内伝播が確認された。

従来、心臓血管外科手術では、手術部位感染予防抗菌薬としてアンピシリン/スルバクタム(ampicillin/sulbactam:以下、ABPC/SBT)が使用されていたが、抗菌薬供給不足により2019年5月1日からクリンダマイシン(clindamycin:以下、CLDM)が使用された。そこで、予防抗菌薬変更前の2019年3～4月に手術を受けた28例をABPC/SBT群、変更後の同年5～6月に手術を受けた20例をCLDM群とし、予防抗菌薬変更が及ぼす影響を調査した。手術部位感染発生例数はABPC/SBT群0例、CLDM群1例で、両群間に統計学的な有意差はなかったが、他剤への変更例数はCLDM群で有意に高かった。本検討よりCLDM群は、抗菌スペクトラムに該当しない原因菌による術後感染症が発生したため、CLDMを使用せざるを得ない場合は、これらの菌種による術後感染症の発生に注意する必要がある。(著者抄録)

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12890-020-01367-5

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Congenital bronchial atresia is a rare pulmonary abnormality characterized by the disrupted communication between the central and the peripheral bronchus and is typically asymptomatic. Although it can be symptomatic especially when infections occur in the involved areas, fungal infections are rare complications in patients with bronchial atresia. We report a case of congenital bronchial atresia complicated by a fungal infection. CASE PRESENTATION: A 30-year-old man with no previous history of immune dysfunction was brought to a nearby hospital and diagnosed with a left lung abscess. Although antimicrobial treatment was administered, it was ineffective, and he was transferred to our hospital. Since diagnostic imaging findings and bronchoscopy suggested congenital bronchial atresia and a fungal infection, he was treated with voriconazole and surgical resection was subsequently performed. A tissue culture detected Aspergillus fumigatus and histopathological findings were compatible with bronchial atresia. After discharge, he remained well and voriconazole was discontinued 5 months after the initiation of therapy. CONCLUSION: Bronchial atresia is a rare disease that is seldom complicated by a fungal infection, which is also a rare complication; however, physicians should consider fungal infections in patients with bronchial atresia who present with infections resistant to antimicrobial treatment.

DOI： 10.1186/s12890-020-01367-5

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s15010-020-01545-x

PubMed

DOI： 10.11534/jsmm.62.suppl1.0_55_3

CiNii Article

DOI： 10.11534/jsmm.62.suppl1.0_79

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>A 73-year-old man previously treated with rituximab for his mucosa-associated lymphoid tissue lymphoma suffered a suboptimal humoral immune response against an acquired SARS-CoV-2 infection. A detailed serological description revealed discrepant antigen-specific humoral immune responses. The titer of spike-targeting, "viral-neutralizing" antibodies remained below the detection level, in contrast to the anti-nucleocapsid, "binding" antibody response, which was comparable in both magnitude and kinetics. Accordingly, viral neutralizability and clearance was delayed, leading to prolonged RNAemia and persistent pneumonia. The present case highlights the need to closely monitor this unique population of recipients of B-cell-targeted therapies for their neutralizing antibody responses against SARS-CoV-2. </p>

DOI： 10.2169/internalmedicine.7884-21

PubMed

CiNii Article

DOI： 10.1093/qjmed/hcaa240

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jgar.2020.10.024

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/qjmed/hcaa240

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: Stenotrophomonas maltophilia causes severe haemorrhagic pneumonia with a reported mortality rate of 100%. However, currently there are no available mouse models of haemorrhagic pneumonia. In the present study, we generated a mouse model of haemorrhagic pneumonia and subjected the animals to treatment with levofloxacin and moxifloxacin to determine whether this model can be used to determine therapeutic effects. METHODS: Stenotrophomonas maltophilia was transtracheally administered to mice immunosuppressed with cyclophosphamide. We confirmed the pathological status of the S. maltophilia isolate and assessed whether the therapeutic effects of quinolone antibiotics could be studied using the model. Levofloxacin and moxifloxacin were administered to evaluate survival rate, bacterial load in the lungs and cardiac blood, as well as pathological changes in diseased lungs compared with those of the control group. RESULTS: Haemorrhagic pneumonia developed within 16-24 h after bacterial infection and was confirmed pathologically. Levofloxacin and moxifloxacin significantly improved survival rates, decreased the bacterial load in lungs and cardiac blood, and improved haemorrhagic pneumonia as indicated by pathological examination. CONCLUSIONS: We established a mouse model of rapidly progressive fatal haemorrhagic pneumonia caused by S. maltophilia that is useful for determining the therapeutic effect of various agents. We believe that this model will prove useful to further elucidate the mechanisms underlying haemorrhagic pneumonia as well as in the design and development of novel therapeutic modalities and targets.

DOI： 10.1016/j.jgar.2020.10.024

PubMed

DOI： 10.3999/jscpt.51.325

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijid.2020.08.013

PubMed

Publishing type：Research paper (scientific journal)  

症例は40歳代女性で、末期腎不全にて維持血液透析中であった。201X年第13病日から第94病日まで、ダプトマイシン(DAP)を、月曜日および水曜日には270mg(6mg/kg)を1日1回30分かけて透析後に点滴静注し、金曜日は400mg(9mg/kg)を同様に点滴静注した。退院時のMRIでは硬膜外膿瘍は縮小しており、DAP投与期間中、クレアチンキナーゼ値はほぼ正常範囲(20〜150IU/L)を推移し、横紋筋融解症およびその他の副作用は見られなかった。投与開始10日目から12日目に採血して得られた血中濃度は、第5回目の投与開始前14.9μg/mL、投与終了5分後94.5μg/mL、投与終了4.6時間後53.5μg/mL、投与終了27.6時間後29.7μg/mL。第6回目の投与開始前13.4μg/mL、投与終了13分後179.5μg/mL、投与終了3.9時間後88.7μg/mLであった。翌週の(月曜日)の投与前の他は予測値11.0μg/mLであった。血中濃度推移をシミュレーションした結果より、週末1.5倍に増量することに意義があると考えられた。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

OBJECTIVES: Previously, cases of positive blood cultures were reported by a microbiological technologist (MT) to an attending physician (AP), and the AS team provided medical assistance by grasping the situation at the morning meeting the next day. Since April 2018, MTs have reported positive blood cultures to an infectious disease physician (IDP) who proposed management approach to the AP and provided weekend support. This study assessed the effectiveness of blood culture reports provided by IDPs to APs on outcomes of bacteremia, including cases of weekend onset. METHODS: Patient characteristics and prognoses before (October 2017 to March 2018) and after intervention (April to September 2018) were compared. RESULTS: The pre- and post-intervention groups were comprised of 134 and 161 patients, respectively. Patients were more likely to be older (over 65 years old) in the post-intervention group (P < 0.05).There were no significant differences in infection severity between two groups. The rate of de-escalation increased significantly from 38.1% to 57.8% (p = 0.001). The rates of 28-day and in-hospital mortality reduced following the intervention (21.3% vs. 8.2%, 32.8% vs. 10.6%: P = 0.004 and P < 0.001, respectively). In-hospital mortality for cases with weekend onset also reduced following the intervention (33.3% vs. 12.9%, P = 0.01). Sepsis was a poor prognostic factor (OR: 8.070, 95%CI: 3.320-19.600, P < 0.001) and intervention was a good prognostic factor (OR: 0.311, 95%CI: 0.142-0.680, P = 0.003) affecting 28-day mortality in multivariate analysis. CONCLUSIONS: Changes to blood culture results reporting protocol can improve outcomes of bacteremia, including cases of weekend onset.

DOI： 10.1016/j.ijid.2020.08.013

PubMed

症例は40歳代女性で、末期腎不全にて維持血液透析中であった。201X年第13病日から第94病日まで、ダプトマイシン(DAP)を、月曜日および水曜日には270mg(6mg/kg)を1日1回30分かけて透析後に点滴静注し、金曜日は400mg(9mg/kg)を同様に点滴静注した。退院時のMRIでは硬膜外膿瘍は縮小しており、DAP投与期間中、クレアチンキナーゼ値はほぼ正常範囲(20～150IU/L)を推移し、横紋筋融解症およびその他の副作用は見られなかった。投与開始10日目から12日目に採血して得られた血中濃度は、第5回目の投与開始前14.9μg/mL、投与終了5分後94.5μg/mL、投与終了4.6時間後53.5μg/mL、投与終了27.6時間後29.7μg/mL。第6回目の投与開始前13.4μg/mL、投与終了13分後179.5μg/mL、投与終了3.9時間後88.7μg/mLであった。翌週の(月曜日)の投与前の他は予測値11.0μg/mLであった。血中濃度推移をシミュレーションした結果より、週末1.5倍に増量することに意義があると考えられた。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Mucormycosis is a deep-seated fungal infection that mainly develops in patients with severe immunodeficiencies such as those with malignant hematological diseases. Despite poor prognosis, there is no reliable and minimally invasive diagnostic method-such as serodiagnosis-for making a clinical decision regarding the condition. As early diagnosis and early treatment improve the prognosis of mucormycosis, the development of a sensitive early diagnostic method is important. We had previously identified a Rhizopus-specific antigen (RSA) by signal sequence trapping and retrovirus-mediated expression (SST-REX), and evaluated its utility as a diagnostic antigen by constructing a sandwich enzyme-linked immunosorbent assay (ELISA) system to detect serum RSA levels in inoculated mice. In this study, we used the RSA-specific rabbit monoclonal antibodies generated by novel hybridoma technology to improve the sensitivity of the ELISA system. We observed an increase in serum and bronchoalveolar lavage fluid (BALF) levels of RSA in mouse model 1 day after inoculation, suggesting that this newly developed monoclonal antibody-based ELISA system may be useful for the diagnosis of mucormycosis in the early stages of infection. In addition, we measured RSA levels in human serum and BALF, and found that serum RSA level was higher in mucormycosis patients (15.1 ng/ml) than that in invasive pulmonary aspergillosis patients (0.53 ng/ml) and the negative control (0.49 ng/ml). Our results suggest that RSA may be a powerful tool for the diagnosis of pulmonary mucormycosis, and its differentiation from other deep-seated mycoses such as aspergillosis.

DOI： 10.1093/mmy/myaa001

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2020.05.001

PubMed

Publishing type：Research paper (scientific journal)  

症例は59歳女性で、白血球増加と血小板増加を主訴とした。入院初日(HD1)、白血球・血小板増加、LDH、CRP、AST、ALT値上昇が認められた。HD4に実施したIGRAとT-SPOT.TB試験は陰性であった。骨髄生検により有意な線維症を伴う骨髄球過形成、巨核球過形成が認められた。蛍光in situハイブリダイゼーションによりフィラデルフィア転座が検出された。造影CTにより大量の腹水と肝脾腫大が認められた。HD9に血中のMajor BCR/ABL1 mRNA(IS)の陽性所見に基づいて慢性骨髄性白血病と診断した。HD22の腹腔穿刺により半透明の黄色い液体が認められ、アデノシンデアミナーゼ値はカットオフ値以上であった。HD18に、血清中に極めて高値の可溶性インターロイキン2受容体(sIL-2R)値が観察された。心肺機能低下のため悪性リンパ腫を疑い、HD29にメチルプレドニゾロンパルス療法を開始したが、結核の家族歴があったことからHD32にレボフロキサシン、イソニアジド、ストレプトマイシンを静脈内投与した。腹水の培養検査結果に基づき、HD39に結核性腹膜炎と診断した。抗結核治療により血清中のsIL-2R値は顕著に低下し、腹水量も改善した。

International / domestic magazine：International journal  

Tuberculous peritonitis is difficult to diagnose due to the disadvantages of ascitic culture and peritoneal biopsy. Although previous reports suggested that very high serum soluble interleukin-2 receptor (sIL-2R) levels may reflect the clinical activity of tuberculosis, little is known about the diagnostic utility of serum sIL-2R for tuberculous peritonitis. We describe a case of tuberculous peritonitis with chronic myelogenous leukemia. The abnormally high serum sIL-2R value and negative findings for other possible causes including lymphoma suggested tuberculous peritonitis and we administered anti-tuberculosis treatment before definitive diagnosis. Abnormally high serum sIL-2R levels may contribute to earlier diagnosis of tuberculous peritonitis, along with ruling out other potential differential diagnoses.

DOI： 10.1016/j.jiac.2020.05.001

PubMed

症例は59歳女性で、白血球増加と血小板増加を主訴とした。入院初日(HD1)、白血球・血小板増加、LDH、CRP、AST、ALT値上昇が認められた。HD4に実施したIGRAとT-SPOT.TB試験は陰性であった。骨髄生検により有意な線維症を伴う骨髄球過形成、巨核球過形成が認められた。蛍光in situハイブリダイゼーションによりフィラデルフィア転座が検出された。造影CTにより大量の腹水と肝脾腫大が認められた。HD9に血中のMajor BCR/ABL1 mRNA(IS)の陽性所見に基づいて慢性骨髄性白血病と診断した。HD22の腹腔穿刺により半透明の黄色い液体が認められ、アデノシンデアミナーゼ値はカットオフ値以上であった。HD18に、血清中に極めて高値の可溶性インターロイキン2受容体(sIL-2R)値が観察された。心肺機能低下のため悪性リンパ腫を疑い、HD29にメチルプレドニゾロンパルス療法を開始したが、結核の家族歴があったことからHD32にレボフロキサシン、イソニアジド、ストレプトマイシンを静脈内投与した。腹水の培養検査結果に基づき、HD39に結核性腹膜炎と診断した。抗結核治療により血清中のsIL-2R値は顕著に低下し、腹水量も改善した。

Publishing type：Research paper (scientific journal)  

2016年2月〜8月に気道感染症から分離された病原菌の抗菌薬感受性に関する全国調査を実施した。全国32の医療機関から送付された1104株のうち、MALDI-TOF MS法と表現型法により目的の7菌種と再同定された1062株を試験に供した。42種の抗菌薬感受性試験、β-ラクタマーゼ産生性、基質特異性拡張型β-ラクタマーゼ(ESBL)産生性を調べた。1062株の内訳は、Staphylococcus aureus 143株、Streptococcus pneumoniae 210株、S.pyogenes 17株、Haemophilus influenzae 248株、Moraxella catarrhalis 151株、Klebsiella pneumoniae 134株、Pseudomonas aeruginosa 159株であった。S.aureus分離株の48.3%はMRSAであった。S.pneumoniae分離株の99.5%はペニシリン系に感受性であった。H.influenzae分離株の14.1%はβ-ラクタマーゼ産生アンピシリン耐性菌で、41.1%はβ-ラクタマーゼ非産生アンピシリン耐性菌であった。K.pneumoniae分離株の4.5%がESBLであった。Pseudomonas aeruginosa分離株の0.6%がメタロβ-ラクタマーゼ産生菌であった。

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2020.05.006

PubMed

2016年2月～8月に気道感染症から分離された病原菌の抗菌薬感受性に関する全国調査を実施した。全国32の医療機関から送付された1104株のうち、MALDI-TOF MS法と表現型法により目的の7菌種と再同定された1062株を試験に供した。42種の抗菌薬感受性試験、β-ラクタマーゼ産生性、基質特異性拡張型β-ラクタマーゼ(ESBL)産生性を調べた。1062株の内訳は、Staphylococcus aureus 143株、Streptococcus pneumoniae 210株、S.pyogenes 17株、Haemophilus influenzae 248株、Moraxella catarrhalis 151株、Klebsiella pneumoniae 134株、Pseudomonas aeruginosa 159株であった。S.aureus分離株の48.3%はMRSAであった。S.pneumoniae分離株の99.5%はペニシリン系に感受性であった。H.influenzae分離株の14.1%はβ-ラクタマーゼ産生アンピシリン耐性菌で、41.1%はβ-ラクタマーゼ非産生アンピシリン耐性菌であった。K.pneumoniae分離株の4.5%がESBLであった。Pseudomonas aeruginosa分離株の0.6%がメタロβ-ラクタマーゼ産生菌であった。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.

DOI： 10.1016/j.jiac.2020.05.006

PubMed

<p>We implemented “Prospective audit and Feedback” as core strategy of ASP. We evaluated the effectiveness of surgical infection treatment for all bacteremia and Bacteroides, which are frequently the cause of surgical infections. As a result, the rate of two sets of blood culture increased and the in–hospital mortality rate of bacteremia was significantly improved (34.9％→23.1％: P＝0.04). In Bacteroides bacteremia, AST activity decreased the frequency of carbapenem agents used in empirical treatment and increased TAZ/PIPC. In addition, the de–escalation rate in definitive therapy increased (9.7％→34.8％: P=0.04). No obvious change in susceptibility to Bacteroides was observed. The prognosis of bacteremia tended to be improved. From the above, it was shown that the AST activities in our hospital is effective in the treatment of surgical infectious diseases.</p>

DOI： 10.24679/gekakansen.17.4_172

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.anaerobe.2020.102214

PubMed

Publishing type：Research paper (scientific journal)  

当院ではASPとして「早期モニタリングとフィードバック」と「条件付き届出制」を採用している。今回外科感染症診療への有効性を菌血症全体と外科感染症の原因菌として頻度が高いBacteroidesを対象に評価を行った。その結果血液培養2セット率は上昇し,菌血症の院内死亡率は有意に改善した(34.9%→23.1%:P=0.04)。Bacteroides菌血症においてはAST活動により,経験的治療におけるカルバペネム系薬の使用頻度の減少,TAZ/PIPCの増加がみられた。また,標的治療におけるde-escalation率が上昇した(9.7%→34.8%:P=0.04)。感受性には明らかな変化はみられなかった。菌血症の予後は改善傾向であった。以上より当院でのAST活動は外科感染症診療において有効であることが示された。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The effect of antimicrobial stewardship (AS) on anaerobic bacteremia is uncertain. This study aimed to assess the effect of interventions by the AS team (AST) on clinical and microbiological outcomes and antimicrobial use. An AS program was introduced at Osaka City University Hospital in January 2014; an interdisciplinary AST was established. We enrolled patients with anaerobic bacteremia between January 2009 and December 2018. Patients were classified into the pre-intervention group (from January 2009 to December 2013) and the post-intervention group (from January 2014 to December 2018). A significant decrease in definitive carbapenem use (P = 0.0242) and an increase in empiric tazobactam/piperacillin use (P = 0.0262) were observed in the post-intervention group. The de-escalation rate increased significantly from 9.38% to 32.7% (P = 0.0316) in the post-intervention group. The susceptibility of Bacteroides species and 30-day mortality did not worsen in the post-intervention group. These results showed that interventions by an AST can reduce carbapenem use and increase the de-escalation rate without worsening patient outcomes.

DOI： 10.1016/j.anaerobe.2020.102214

PubMed

当院ではASPとして「早期モニタリングとフィードバック」と「条件付き届出制」を採用している。今回外科感染症診療への有効性を菌血症全体と外科感染症の原因菌として頻度が高いBacteroidesを対象に評価を行った。その結果血液培養2セット率は上昇し,菌血症の院内死亡率は有意に改善した(34.9%→23.1%:P=0.04)。Bacteroides菌血症においてはAST活動により,経験的治療におけるカルバペネム系薬の使用頻度の減少,TAZ/PIPCの増加がみられた。また,標的治療におけるde-escalation率が上昇した(9.7%→34.8%:P=0.04)。感受性には明らかな変化はみられなかった。菌血症の予後は改善傾向であった。以上より当院でのAST活動は外科感染症診療において有効であることが示された。(著者抄録)

<p>A 38-year-old man diagnosed as having COVID-19 pneumonia was transferred to our hospital from another hospital. The patient had received favipiravir at the previous hospital, and as he still had severe respiratory dysfunction, we added hydroxychloroquine and azithromycin to the treatment regimen for COVID-19 pneumonia at our hospital. The respiratory status improved gradually with the treatment and the patient began to be weaned from mechanical ventilation. However, on the 5^thhospital day, the patient developed ventricular fibrillation (Vf) and cardiac arrest, with return of spontaneous circulation (ROSC) 2 minutes after the start of cardiopulmonary resuscitation. An electrocardiogram recorded after the ROSC showed not QT interval prolongation, but first-degree atrioventricular block. Nevertheless, because both hydroxychloroquine and azithromycin could cause QT interval prolongation, both were discontinued and the Vf did not recur. The patient was transferred to another hospital after extubation and had no neurological deficit. Herein, we report a patient with COVID-19 pneumonia who developed Vf while being treated with hydroxychloroquine,azithromycin and favipiravir.</p>

DOI： 10.11150/kansenshogakuzasshi.94.600

CiNii Article

DOI： 10.11477/mf.1542202412

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12879-020-05205-1

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Extended use of oseltamivir in an immunocompromised host could reportedly induce neuraminidase gene mutation possibly leading to oseltamivir-resistant influenza A/H3N2 virus. To our knowledge, no report is available on the clinical course of a severely immunocompromised patient with a dual E119D/R292K neuraminidase mutated-influenza A/H3N2 during the administration of peramivir. CASE PRESENTATION: A 49-year-old male patient was admitted for second allogeneic hematopoietic cell transplantation for active acute leukemia. The patient received 5 mg prednisolone and 75 mg cyclosporine and had severe lymphopenia (70/μL). At the time of hospitalization, the patient was diagnosed with upper tract influenza A virus infection, and oseltamivir treatment was initiated immediately. However, the patient was intolerant to oseltamivir. The following day, treatment was changed to peramivir. Despite a total period of neuraminidase-inhibitor administration of 16 days, the symptoms and viral shedding continued. Changing to baloxavir marboxil resolved the symptoms, and the influenza diagnostic test became negative. Subsequently, sequence analysis of the nasopharyngeal specimen revealed the dual E119D/R292K neuraminidase mutant influenza A/H3N2. CONCLUSIONS: In a highly immunocompromised host, clinicians should take care when peramivir is used for extended periods to treat influenza virus A/H3N2 infection as this could potentially leading to a dual E119D/R292K substitution in neuraminidase protein. Baloxavir marboxil may be one of the agents that can be used to treat this type of mutated influenza virus infection.

DOI： 10.1186/s12879-020-05205-1

PubMed

Publishing type：Research paper (scientific journal)  

38歳男。発熱、咳嗽にて前医を受診した。異型肺炎の疑いで加療されるも呼吸困難が増強し、PCR検査でSARS-CoV-2陽性が判明した。人工呼吸器管理の上、新型コロナウイルス感染症(COVID-19)に対してファビピラビル、ヒドロキシクロロキン、アジスロマイシンを併用したが、治療中に突然心室細動をきたし、心室細動の原因として薬剤性のQTc延長からR on Tとなった可能性やCOVID-19に伴う心筋炎の可能性を考え、ヒドロキシクロロキン、アジスロマイシン、デクスメデトミジンを中止した。洞調律へ回復後の12誘導心電図では1度房室ブロックを認めるのみでQT延長はみられず、その後は不整脈の出現なく経過し、呼吸状態も安定していた。

38歳男。発熱、咳嗽にて前医を受診した。異型肺炎の疑いで加療されるも呼吸困難が増強し、PCR検査でSARS-CoV-2陽性が判明した。人工呼吸器管理の上、新型コロナウイルス感染症(COVID-19)に対してファビピラビル、ヒドロキシクロロキン、アジスロマイシンを併用したが、治療中に突然心室細動をきたし、心室細動の原因として薬剤性のQTc延長からR on Tとなった可能性やCOVID-19に伴う心筋炎の可能性を考え、ヒドロキシクロロキン、アジスロマイシン、デクスメデトミジンを中止した。洞調律へ回復後の12誘導心電図では1度房室ブロックを認めるのみでQT延長はみられず、その後は不整脈の出現なく経過し、呼吸状態も安定していた。

Publishing type：Research paper (scientific journal)  

DOI： 10.1186/s12879-020-05136-x

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

DOI： 10.1186/s12879-020-05136-x

PubMed

DOI： 10.2169/internalmedicine.4117-19

<p><b>Objective </b>Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs. </p><p><b>Methods </b>A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group. </p><p><b>Results </b>A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment ≥2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002). </p><p><b>Conclusion </b>The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice. </p>

DOI： 10.2169/internalmedicine.4117-19

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

臨床診療のA型インフルエンザ患者において、バロキサビルとノイラミニダーゼ阻害薬(NAI)の有効性を比較した。2018〜2019年のインフルエンザシーズンに大阪府の50施設でバロキサビルまたはNAIが処方された患者900例を対象に郵送による質問票調査を行い、A型インフルエンザ患者295例のデータを解析した。バロキサビル投与患者は111例(男性50例、女性60例、性別不明1例、2〜72歳)、NAI投与患者は184例(男性73例、女性108例、性別不明3例、0〜91歳)であった。多変量調整後、2日以内の発熱緩和の関連因子は、バロキサビル治療、発症から治療開始までの期間≧2.5日であった。バロキサビル投与患者はNAI投与患者に比し、発熱緩和までの期間が有意に短縮した(1.94±0.09 vs.2.35±0.08日)。臨床診療のA型インフルエンザ患者において、バロキサビルはNAIよりも有効性が高いことが示された。

Publishing type：Research paper (scientific journal)  

症例は62歳男性で、50日前、慢性Stanford B型大動脈解離のためfrozen elephant trunk修復術が施行された。術後29日目に退院したが、その8日後から発熱と全身疲労が発現し、CTで縦隔内と左腋窩動脈周辺の人工血管周囲に膿瘍が認められた。人工血管感染と診断し、入院当日に左鎖骨下のオープンドレナージ、その翌日に縦隔ドレナージを行った。入院5日目に膿瘍の膿汁培養でStaphylococcus schleiferiが判明した。抗生物質全身投与と局所陰圧閉鎖療法を行ったが感染をコントロールできなかったため、緊急手術として、人工血管による上行大動脈と大動脈弓の置換術、大網弁移植、自家腸骨動脈を用いた左鎖骨下動脈再建術を行った。術後4日目にリネゾリド(LZD)の投与を開始し、術後33日目にLZDの副作用のためダプトマイシンに変更した。術後80日目に経口ミノサイクリンに切り替え、術後115日目に介護施設に移った。

Publishing type：Research paper (scientific journal)  

59歳女。腕と背中の痛みおよび両手指関節炎を10年間患っており、血清中のリウマチ因子検査で関節リウマチと診断され、治療を受けていた。また、2年前に心房細動と左室肥大を発症していた。最近、耳鳴りや胃の不快感に気づき、失神様発作を発症した。定期検査で尿沈渣中にマルベリー小体(MB)が検出され、ファブリー病(FD)の疑いでα-ガラクトシダーゼ遺伝子を調べたところ、変異対立遺伝子(exon6のDel 1b)を持つヘテロ接合体であった。MBと変異したα-ガラクトシダーゼ遺伝子の検出よりFDと診断され、アガルシダーゼベータ(Fabrazyme)で酵素補充療法(ERT)による治療を開始したところ、症状は徐々に改善した。しかし、左室肥大は残っており、ERTのため定期通院とした。

Publishing type：Research paper (scientific journal)  

DOI： 10.18926/AMO/59959

PubMed

International / domestic magazine：Domestic journal  

A 62-year-old Japanese male presented with graft infection by Staphylococcus schleiferi 50 days after debranching of the left subclavian artery and frozen elephant trunk repair for the entry closure of a Stanford type B aortic dissection. The graft was removed, and the patient was successfully treated using in situ reconstruction of the arch with omental flap coverage, removal of the debranching graft, autologous iliac artery grafting, and longterm antibiotics. Domino reconstruction of the infected debranching graft using autologous external iliac artery and a Dacron graft can thus be a good option in similar cases.

DOI： 10.18926/AMO/59959

PubMed

臨床診療のA型インフルエンザ患者において、バロキサビルとノイラミニダーゼ阻害薬(NAI)の有効性を比較した。2018～2019年のインフルエンザシーズンに大阪府の50施設でバロキサビルまたはNAIが処方された患者900例を対象に郵送による質問票調査を行い、A型インフルエンザ患者295例のデータを解析した。バロキサビル投与患者は111例(男性50例、女性60例、性別不明1例、2～72歳)、NAI投与患者は184例(男性73例、女性108例、性別不明3例、0～91歳)であった。多変量調整後、2日以内の発熱緩和の関連因子は、バロキサビル治療、発症から治療開始までの期間≧2.5日であった。バロキサビル投与患者はNAI投与患者に比し、発熱緩和までの期間が有意に短縮した(1.94±0.09 vs.2.35±0.08日)。臨床診療のA型インフルエンザ患者において、バロキサビルはNAIよりも有効性が高いことが示された。

症例は62歳男性で、50日前、慢性Stanford B型大動脈解離のためfrozen elephant trunk修復術が施行された。術後29日目に退院したが、その8日後から発熱と全身疲労が発現し、CTで縦隔内と左腋窩動脈周辺の人工血管周囲に膿瘍が認められた。人工血管感染と診断し、入院当日に左鎖骨下のオープンドレナージ、その翌日に縦隔ドレナージを行った。入院5日目に膿瘍の膿汁培養でStaphylococcus schleiferiが判明した。抗生物質全身投与と局所陰圧閉鎖療法を行ったが感染をコントロールできなかったため、緊急手術として、人工血管による上行大動脈と大動脈弓の置換術、大網弁移植、自家腸骨動脈を用いた左鎖骨下動脈再建術を行った。術後4日目にリネゾリド(LZD)の投与を開始し、術後33日目にLZDの副作用のためダプトマイシンに変更した。術後80日目に経口ミノサイクリンに切り替え、術後115日目に介護施設に移った。

59歳女。腕と背中の痛みおよび両手指関節炎を10年間患っており、血清中のリウマチ因子検査で関節リウマチと診断され、治療を受けていた。また、2年前に心房細動と左室肥大を発症していた。最近、耳鳴りや胃の不快感に気づき、失神様発作を発症した。定期検査で尿沈渣中にマルベリー小体(MB)が検出され、ファブリー病(FD)の疑いでα-ガラクトシダーゼ遺伝子を調べたところ、変異対立遺伝子(exon6のDel 1b)を持つヘテロ接合体であった。MBと変異したα-ガラクトシダーゼ遺伝子の検出よりFDと診断され、アガルシダーゼベータ(Fabrazyme)で酵素補充療法(ERT)による治療を開始したところ、症状は徐々に改善した。しかし、左室肥大は残っており、ERTのため定期通院とした。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Acinetobacter baumannii ATCC 19606T, which is often used in genetic studies as a routine model microorganism, belongs to sequence type 52 (ST52), showing beta-lactam resistance. We present the complete 3.996-Mbp genome sequence (1 chromosome plus 2 plasmids), generated by combining long-read (MinION) and short-read (MiniSeq) sequencing data.

DOI： 10.1128/MRA.00289-20

PubMed

DOI： 10.11477/mf.1437200357

Publishing type：Research paper (scientific journal)  

DOI： 10.1128/MRA.00289-20

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/mmy/myaa001

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: There are limited data for direct comparisons of the efficacy of oral itraconazole (ITCZ) and oral voriconazole (VRCZ) therapy in the treatment of chronic pulmonary aspergillosis (CPA). METHODS: We conducted a retrospective, follow-up, observational study of CPA patients enrolled in 2 previous multicenter trials. RESULTS: Of the 273 CPA patients, 59 and 101 patients started maintenance therapy with oral ITCZ and oral VRCZ, respectively, just after the end of acute intravenous therapy in each trial. At the end of the observation period in this follow-up study (median observation period, 731 days), the percentage of patients who showed improvement was lower in the ITCZ group than in the VRCZ group (18.2% vs 40.0%). However, after including stable patients, the percentages were 50.9% and 52.6%, respectively, in the ITCZ and VRCZ groups, which were not significantly different (P = .652). Multivariable Cox regression analysis showed no significant influence of the choice of initial maintenance treatment (ITCZ or VRCZ) on overall mortality as well as CPA-associated mortality. Multivariable logistic regression showed that oral ITCZ selection for initial maintenance therapy was an independent risk factor for hospital readmission and switching to other antifungal agents (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.3-7.5 and OR, 5.7; 95% CI, 2.0-15.7, respectively). CONCLUSIONS: Oral VRCZ for initial maintenance therapy showed better effectiveness than oral ITCZ for clinical improvement in CPA patients. There was no difference in crude mortality between initial maintenance therapy with VRCZ and ITCZ, especially in elderly CPA patients. CLINICAL TRIALS REGISTRATION: UMIN000007055.

DOI： 10.1093/cid/ciz287

PubMed

DOI： 10.2169/naika.109.293

CiNii Article

Publishing type：Research paper (scientific journal)  

日本の日常診療におけるメチシリン耐性黄色ブドウ球菌(MRSA)肺炎の臨床成績を調査し、臨床的失敗に関する危険因子とMRSA肺炎患者の死亡率を決定する前向き観察研究を日本の48施設で共同施行した。MRSA肺炎の成人患者199名(男性160名、年齢四分位範囲69〜83歳)が適格とされたが、その肺炎の内訳は、医療・介護関連肺炎が95名、院内肺炎が76名、市中肺炎が25名、などであった。初期治療に用いられた抗MRSA薬の種類別では、バンコマイシン(VCM)が135名、リネゾリドが36名、テイコプラニンが22名であった。治癒判定時点での全臨床的失敗率は51.1%、30日死亡率は33.7%であった。VCM治療集団を対象に多変量ロジスティック回帰分析を行った。その結果、臨床的失敗の危険因子として白血球数異常(オッズ比4.34,95%CI 1.31〜14.39)が示された。また死亡に関する危険因子としては治療薬物モニタリング(TDM)が為されていないこと(オッズ比3.10,95%CI 1.35〜7.12)とC反応性蛋白質レベルの異常高値(3.54、1.26〜9.92)が明らかになった。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia. This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed. In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31-14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35-7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26-9.92) were risk factors for mortality. In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.

DOI： 10.1016/j.jiac.2019.08.018

PubMed

日本の日常診療におけるメチシリン耐性黄色ブドウ球菌(MRSA)肺炎の臨床成績を調査し、臨床的失敗に関する危険因子とMRSA肺炎患者の死亡率を決定する前向き観察研究を日本の48施設で共同施行した。MRSA肺炎の成人患者199名(男性160名、年齢四分位範囲69～83歳)が適格とされたが、その肺炎の内訳は、医療・介護関連肺炎が95名、院内肺炎が76名、市中肺炎が25名、などであった。初期治療に用いられた抗MRSA薬の種類別では、バンコマイシン(VCM)が135名、リネゾリドが36名、テイコプラニンが22名であった。治癒判定時点での全臨床的失敗率は51.1%、30日死亡率は33.7%であった。VCM治療集団を対象に多変量ロジスティック回帰分析を行った。その結果、臨床的失敗の危険因子として白血球数異常(オッズ比4.34,95%CI 1.31～14.39)が示された。また死亡に関する危険因子としては治療薬物モニタリング(TDM)が為されていないこと(オッズ比3.10,95%CI 1.35～7.12)とC反応性蛋白質レベルの異常高値(3.54、1.26～9.92)が明らかになった。

DOI： 10.2169/internalmedicine.3358-19

<p><b>Objective </b>Hemorrhagic pneumonia due to <i>Stenotrophomonas maltophilia</i> (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. </p><p><b>Methods </b>This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. </p><p><b>Patients </b>All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. </p><p><b>Results </b>The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). </p><p><b>Conclusion </b>Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation. </p>

DOI： 10.2169/internalmedicine.3358-19

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1002/jgf2.286

PubMed

Publishing type：Research paper (scientific journal)  

Stenotrophomonas maltophilia(SM)菌血症で入院した35例の医療データを用いて、SMによる出血性肺炎の予測因子を後向きに評価した。4例(男性3例、女性1例、中央値56.2歳)で出血性肺炎を認め、31例(男性19例、女性12例、中央値59.5歳)は出血性肺炎を認めなかった。出血性肺炎を認めた患者は認めなかった患者に比べて悪性血液疾患の割合が有意に高く(100 vs 38.7%)、血小板減少症の割合が有意に高く(100 vs 38.7%)、30日以内のキノロン系薬使用率が有意に高かった(75 vs 19.4%)。入院中の死亡率は、出血性肺炎を認めた患者100%、認めなかった患者32.3%であった(p=0.02)。悪性血液疾患、血小板減少症、30日以内のキノロン系薬使用歴のあるSM菌血症患者では慎重に治療を行う必要があることが示された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

BACKGROUND: After the A/H1N1 influenza pandemic in 2009, two new drugs against influenza, namely laninamivir and peramivir, were released in 2010 in Japan. We investigated prescription trends of four neuraminidase inhibitors (NAIs), which are laninamivir, peramivir, oseltamivir, and zanamivir, and assessed clinical data related to influenza for 8 years. METHODS: Patients living in Osaka Prefecture and diagnosed with influenza responded to a postcard questionnaire that collected data regarding their demographic characteristics, symptoms including fever, prescribed drugs, and influenza type. RESULTS: Laninamivir was most prescribed to patients aged ≥ 10 years, and oseltamivir was most prescribed to patients aged < 10 years. All four NAIs had similar effects on influenza. Patients with type A influenza experienced fever alleviation earlier than those with type B influenza. Older patients tended to have lower fever. Most seasons had similar results. CONCLUSIONS: Our descriptive epidemiologic study revealed the status of patients with influenza and their medication use.

DOI： 10.1002/jgf2.286

PubMed

ノイラミニダーゼ阻害剤(NAI)であるラニナミビル、ペラミビル、オセルタミビル、ザナミビルの処方傾向を8年にわたって調べ、インフルエンザに関連する臨床データを評価した。インフルエンザと診断された患者に対しアンケート調査を依頼し、人口統計学的特徴、発熱などの症状、処方薬、インフルエンザの種類に関するデータを収集した。その結果、ラニナミビルは10歳以上の患者に最も処方され、オセルタミビルは10歳未満の患者に最も処方されていた。4種類のNAIはいずれもインフルエンザに対して同様の効果を示した。A型インフルエンザの患者はB型インフルエンザの患者よりも早く熱が下がった。高齢患者は発熱時の体温が低い傾向があった。ほとんどの季節で同様の結果となった。

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.2169/naika.109.293

CiNii Article

Publishing type：Research paper (scientific journal)  

<p>A 38-year-old man diagnosed as having COVID-19 pneumonia was transferred to our hospital from another hospital. The patient had received favipiravir at the previous hospital, and as he still had severe respiratory dysfunction, we added hydroxychloroquine and azithromycin to the treatment regimen for COVID-19 pneumonia at our hospital. The respiratory status improved gradually with the treatment and the patient began to be weaned from mechanical ventilation. However, on the 5^thhospital day, the patient developed ventricular fibrillation (Vf) and cardiac arrest, with return of spontaneous circulation (ROSC) 2 minutes after the start of cardiopulmonary resuscitation. An electrocardiogram recorded after the ROSC showed not QT interval prolongation, but first-degree atrioventricular block. Nevertheless, because both hydroxychloroquine and azithromycin could cause QT interval prolongation, both were discontinued and the Vf did not recur. The patient was transferred to another hospital after extubation and had no neurological deficit. Herein, we report a patient with COVID-19 pneumonia who developed Vf while being treated with hydroxychloroquine,azithromycin and favipiravir.</p>

DOI： 10.11150/kansenshogakuzasshi.94.600

CiNii Article

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.61.Suppl1.0_62

CiNii Article

Publishing type：Research paper (scientific journal)  

<p><b>Objective </b>Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs. </p><p><b>Methods </b>A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group. </p><p><b>Results </b>A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment ≥2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002). </p><p><b>Conclusion </b>The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice. </p>

DOI： 10.2169/internalmedicine.4117-19

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.61.Suppl1.0_63_1

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.3314/mmj.20.001

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.61.Suppl1.0_75

CiNii Article

Publishing type：Research paper (scientific journal)  

<p>We implemented "Prospective audit and Feedback" as core strategy of ASP. We evaluated the effectiveness of surgical infection treatment for all bacteremia and Bacteroides, which are frequently the cause of surgical infections. As a result, the rate of two sets of blood culture increased and the in–hospital mortality rate of bacteremia was significantly improved (34.9％→23.1％: P＝0.04). In Bacteroides bacteremia, AST activity decreased the frequency of carbapenem agents used in empirical treatment and increased TAZ/PIPC. In addition, the de–escalation rate in definitive therapy increased (9.7％→34.8％: P=0.04). No obvious change in susceptibility to Bacteroides was observed. The prognosis of bacteremia tended to be improved. From the above, it was shown that the AST activities in our hospital is effective in the treatment of surgical infectious diseases.</p>

DOI： 10.24679/gekakansen.17.4_172

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.3999/jscpt.51.325

CiNii Article

Publishing type：Research paper (scientific journal)  

<p><b>Objective </b>Hemorrhagic pneumonia due to <i>Stenotrophomonas maltophilia</i> (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. </p><p><b>Methods </b>This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. </p><p><b>Patients </b>All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. </p><p><b>Results </b>The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). </p><p><b>Conclusion </b>Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation. </p>

DOI： 10.2169/internalmedicine.3358-19

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p><b>Objective </b>Hemorrhagic pneumonia due to <i>Stenotrophomonas maltophilia</i> (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. </p><p><b>Methods </b>This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. </p><p><b>Patients </b>All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. </p><p><b>Results </b>The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). </p><p><b>Conclusion </b>Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation. </p>

DOI： 10.2169/internalmedicine.3358-19

PubMed

DOI： 10.11534/jsmm.61.suppl1.0_63_1

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

DOI： 10.3314/mmj.20.001

PubMed

CiNii Article

DOI： 10.11534/jsmm.61.suppl1.0_75

CiNii Article

DOI： 10.2169/internalmedicine.3358-19

PubMed

<p>医療の発展に伴い臓器・造血幹細胞移植患者数も増加しているが、術後感染症のマネジメントや感染対策が重要である。造血幹細胞移植患者では、移植前から著明な免疫不全を伴うために感染症を伴うこともあるが、臓器移植においては術前に免疫不全を有することは比較的限られる。一方、臓器移植後には様々な感染症を発症するが、移植後の時期や移植臓器により原因菌に特徴がある。移植初期（移植後4週以内）には、患者の基礎疾患や手術の合併症としての感染症を発症し、細菌や真菌がその主な原因病原体となる。ときに医療関連感染としての耐性菌も関与する。移植中期（移植後１〜６ヶ月）には免疫抑制薬による細胞性免疫不全に伴う日和見感染症が問題となる。ヘルペスウイルスやサイトメガロウイルス、ニューモシスチス肺炎等の予防も重要である。移植後期（６ヶ月以後）では状態が安定し、免疫抑制薬も減量され、予防薬が中止される。一方、レシピエントの多くは院外で生活するために市中感染症の感染対策が必要となる。また、移植臓器特異的な感染症としては、肺移植ではアスペルギルス、肝移植では腸内細菌やカンジダ、腎移植ではサイトメガロウイルス、BKウイルス等による感染症が知られている。講演では臓器移植および造血幹細胞移植に伴う感染症の診断および感染対策について概説する。</p>

DOI： 10.11386/jst.55.supplement_244_1

CiNii Article

DOI： 10.11534/jsmm.61.suppl1.0_62

CiNii Article

DOI： 10.2169/internalmedicine.4117-19

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Objective Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs. Methods A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group. Results A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment ≥2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002). Conclusion The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice.

DOI： 10.2169/internalmedicine.4117-19

PubMed

Publishing type：Research paper (scientific journal)  

Objective Baloxavir marboxil is a novel anti-influenza drug reported to have an early antiviral effect, although it also causes the appearance of variant viruses with a reduced susceptibility to baloxavir. In Japan, four neuraminidase inhibitors (NAIs) have been commonly used to treat patients with influenza. In clinical practice, the differences in the effects of baloxavir and NAIs have not been sufficiently examined. Our objective was to clarify the clinical differences in efficacy between baloxavir and NAIs.Methods A multicenter, observational study was conducted using postcard questionnaires during the 2018-19 influenza season. Patients who were prescribed anti-influenza drugs were provided postcard questionnaires asking about their background characteristics and their body temperatures. The factors associated with the early alleviation of the fever were analyzed, and the duration of the fever was compared between the baloxavir group and the NAI group.Results A total of 295 patients with influenza A, ranging in age from 0-91 years old, were enrolled in this study. A multivariate analysis showed that treatment with baloxavir and a duration from the onset to the start of treatment >= 2.5 days were factors contributing to the early alleviation of the fever from the start of treatment. The duration of the fever was significantly shorter in the baloxavir group than in the NAI group (p=0.002).Conclusion The present survey showed that baloxavir was significantly more effective than NAIs for treating patients with influenza A in clinical practice.

DOI： 10.2169/internalmedicine.4117-19

Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10096-019-03676-y

PubMed

Publishing type：Research paper (scientific journal)  

近年、日本を含めた東・東南アジアを中心として、高粘稠性のKlebsiella pneumoniae(hvKP)が臨床上問題となっている。本菌の高病原性には、莢膜多糖合成遺伝子であるregulator of mucoid phenotype A(rmpA)等の働きによる莢膜多糖の過剰産生が関与している。今までhvKPの高病原性のメカニズムに関する研究は数多くされてきているが、抗病原性療法に焦点をあてた研究はない。我々は、hvKPの高粘稠性を抑制することができる薬剤を既存の抗菌薬の中から探索した。結果、リファンピシン(RFP)に強い粘稠性抑制作用があることを発見した。またRFPは莢膜の厚さを減少させ、さらにrmpAを中心とした莢膜関連遺伝子の転写を抑制することが判明した。以上のことから、リファンピシンが本菌による難治性感染症に対する治療薬として役立つ可能性があることが示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

近年、日本を含めた東・東南アジアを中心として、高粘稠性のKlebsiella pneumoniae(hvKP)が臨床上問題となっている。本菌の高病原性には、莢膜多糖合成遺伝子であるregulator of mucoid phenotype A(rmpA)等の働きによる莢膜多糖の過剰産生が関与している。今までhvKPの高病原性のメカニズムに関する研究は数多くされてきているが、抗病原性療法に焦点をあてた研究はない。我々は、hvKPの高粘稠性を抑制することができる薬剤を既存の抗菌薬の中から探索した。結果、リファンピシン(RFP)に強い粘稠性抑制作用があることを発見した。またRFPは莢膜の厚さを減少させ、さらにrmpAを中心とした莢膜関連遺伝子の転写を抑制することが判明した。以上のことから、リファンピシンが本菌による難治性感染症に対する治療薬として役立つ可能性があることが示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2019.05.026

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Klebsiella pneumoniae bacteremia is a critical clinical presentation that is associated with high mortality. However, extremely few studies have investigated the virulence factors related to mortality of K. pneumoniae bacteremia in patients. The present study elucidated clinical and virulence factors associated with the 30-day mortality of K. pneumoniae bacteremia at a tertiary hospital. The medical records of 129 patients with K. pneumoniae bacteremia admitted to Osaka City University Hospital between January 2012 and December 2018 were retrospectively reviewed. Patient background characteristics, antimicrobial regimens, and prognosis were evaluated. Additionally, virulence factors were assessed using multiplex polymerase chain reaction to elucidate their association with K. pneumoniae. The 30-day mortality was 10.9% in patients with K. pneumoniae bacteremia. The male-to-female ratio, age, and underlying disease did not differ between the non-survivor and survivor groups. Multivariate analysis showed that sepsis (odds ratio (OR), 7.46; p = 0.005) and iutA (OR, 4.47; p = 0.046) were independent predictors associated with the 30-day mortality of K. pneumoniae bacteremia. Despite the relatively low 30-day mortality of patients with K. pneumoniae bacteremia, the treatment of those with sepsis and those infected with K. pneumoniae harboring iutA may require careful management for improving their outcomes.

DOI： 10.1007/s10096-019-03676-y

PubMed

DOI： 10.1016/j.jiac.2019.05.026

近年、日本を含めた東・東南アジアを中心として、高粘稠性のKlebsiella pneumoniae(hvKP)が臨床上問題となっている。本菌の高病原性には、莢膜多糖合成遺伝子であるregulator of mucoid phenotype A(rmpA)等の働きによる莢膜多糖の過剰産生が関与している。今までhvKPの高病原性のメカニズムに関する研究は数多くされてきているが、抗病原性療法に焦点をあてた研究はない。我々は、hvKPの高粘稠性を抑制することができる薬剤を既存の抗菌薬の中から探索した。結果、リファンピシン(RFP)に強い粘稠性抑制作用があることを発見した。またRFPは莢膜の厚さを減少させ、さらにrmpAを中心とした莢膜関連遺伝子の転写を抑制することが判明した。以上のことから、リファンピシンが本菌による難治性感染症に対する治療薬として役立つ可能性があることが示唆された。(著者抄録)

近年、日本を含めた東・東南アジアを中心として、高粘稠性のKlebsiella pneumoniae(hvKP)が臨床上問題となっている。本菌の高病原性には、莢膜多糖合成遺伝子であるregulator of mucoid phenotype A(rmpA)等の働きによる莢膜多糖の過剰産生が関与している。今までhvKPの高病原性のメカニズムに関する研究は数多くされてきているが、抗病原性療法に焦点をあてた研究はない。我々は、hvKPの高粘稠性を抑制することができる薬剤を既存の抗菌薬の中から探索した。結果、リファンピシン(RFP)に強い粘稠性抑制作用があることを発見した。またRFPは莢膜の厚さを減少させ、さらにrmpAを中心とした莢膜関連遺伝子の転写を抑制することが判明した。以上のことから、リファンピシンが本菌による難治性感染症に対する治療薬として役立つ可能性があることが示唆された。(著者抄録)

広域スペクトラム抗菌薬を長期間(7日以上)使用した血流感染(BSI)患者1187名(男725名、女462名)を対象に、抗菌薬適正使用支援チームによる介入が菌血症のアウトカムや抗菌薬感受性、抗菌薬の使用について後ろ向きに検討した。抗菌薬適正使用支援プログラム(ASP)導入前(2011～2013年、492名)と導入後(2014～2016年、695名)に分けて検討した。ASP導入前と後で30日死亡率に有意差はなかったが、ASP導入後の院内死亡率(18.0%、125/695)は導入前(24.8%、122/492)より低下した。ASP導入後の薬剤耐性グラム陰性菌血症の30日死亡率(10.5%、13/124)および院内死亡率(16.1%、20/124)は、導入前(それぞれ20.4%、19/93および28.0%、26/93)より低下した。広域スペクトラム抗菌薬のdays of therapyはタゾバクタム・ピペラシリンを除き減少した。種々の抗菌薬に対する感受性がASP導入後に改善された。

DOI： 10.1016/j.jiac.2019.05.026

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes. This retrospective study enrolled patients with bloodstream infections (BSI) and long-term use of broad-spectrum antibiotics (more than 7 days). The main outcomes were 30-day and in-hospital mortality of patients with BSI. The secondary outcomes were the day of therapy (DOT) and susceptibility of antipseudomonal agents. Cases were classified into two groups: the pre-ASP group comprised cases between 2011 and 2013 and the post-ASP group, between 2014 and 2016. The outcomes were then compared between the two groups. Among the patients with all BSI (n = 1187), no significant differences in 30-day mortality were observed between those in the pre-ASP and post-ASP groups. However, in-hospital mortality was significantly lower in the post-ASP group than that in the pre-ASP group (24.8% vs. 18.0%; P = 0.004). Furthermore, the 30-day and in-hospital mortality of resistant gram-negative bacteraemia was significantly lower (20.4% vs.10.5%; P = 0.04 and 28.0% vs.16.1%; P = 0.03). The DOT of broad-spectrum antibiotics decreased except that of tazobactam/piperacillin. The susceptibilities of tazobactam/piperacillin, ceftazidime, cefepime, sulbactam/cefoperazone, gentamicin, ciprofloxacin levofloxacin, imipenem and meropenem were significantly better. Interventions by the AST can improve the clinical and microbiological outcomes, especially resistant gram-negative bacteria. Furthermore, this effect of our ASP can continue for a long term.

DOI： 10.1016/j.jiac.2019.05.026

PubMed

DOI： 10.2169/naika.108.2268

CiNii Article

<p>The Therapeutic Drug Monitoring (TDM) Guidelines for Antibiotics (the “Revised guidelines”) were revised in June 2016. The Revised guidelines are followed to determine dosage and provide treatment at Osaka City University Hospital. The current study investigated VCM administration before and after the guidelines were revised as well as their effectiveness and safety. The period from January to December 2015 before the guidelines were revised (“before Revision”) and the period from January to December 2017 after the guidelines were revised (“after Revision”) were compared. One hundred and six patients received VCM therapy before Revision, and 184 received VCM therapy after Revision. Initially, 17.4％ of patients had the recommended serum VCM level of 10-15 µg/mL, but that increased to 41.7％ as a result of a pharmacist’s involvement; 72.8％ of patients had serum VCM below 10 µg/mL after Revision. Acute kidney injury (AKI) was evaluated based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The incidence of AKI was 12.3％ before Revision and 5.4％ after Revision, so it was significantly lower before Revision. The 30-day survival rate was 94.6％ before Revision and 95.3％ after Revision, so the rate did not differ significantly.</p><p>When VCM therapy was administered in accordance with the Revised guidelines, the initial serum trough level of VCM was lower than 10 µg/mL in most patients, and VCM slightly affected the kidneys. Most patients had a serum VCM of 10-15 µg/mL as a result of a pharmacist’s intervention, suggesting that the serum VCM level did not affect prognosis.</p>

DOI： 10.5649/jjphcs.45.576

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

待機的腹腔鏡下脾摘出術(LS)後の手術転帰を後ろ向きに検討した。2001〜2015年に脾機能亢進症や脾臓腫瘍等に対し当該手術を施行された患者123例(男性48例、女性75例、平均59.5±11.8歳)を対象に、手術手技標準化前(初期)と標準化後(後期)の手術転帰と手術部位感染(SSI)に対する予防的抗生物質(PA)投与の影響について検討した。術後合併症は、創傷感染、門脈幹血栓症、膵瘻、胸水が各1例、術後出血が2例、腸損傷による再手術が1例であった。術後合併症は初期と後期で差は見られなかったが、術中出血量は後期で有意に少なかった。また後期では開腹術への移行例もなかった。SSIは、手術開始1時間前と術中3時間ごとにPA投与を行った群と、それに加え術後24〜72時間に1日2回PA投与を行った群では差は見られなかった。LS後の成績は、術者の手技経験が増加すると共に改善した。また、術前1時間と術中3時間毎のPA投与はSSI予防に十分であることが示唆された。

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

INTRODUCTION: We conducted a retrospective study to investigate the progress of the operative outcome after laparoscopic splenectomy (LS), with a special reference to the administration of prophylactic antibiotics (PA). METHODS: The study included 123 patients who underwent elective LS. Operative outcomes before and after the operative procedure was standardized and the impact of treatment with PA on surgical-site infection were investigated. RESULTS: With regard to complications, wound infection developed in one (0.8%), portal trunk thrombosis in one (0.8%), pancreatic fistula in one (0.8%), postoperative bleeding in two (1.6%), pleural effusion in one (0.8%), and reoperation because of bowel injury in one (0.8%). Although morbidity did not differ between patients in the early (until the end of 2010) and late (after the beginning of 2011) periods, intraoperative blood loss was lower in patients in the late period. During the late period, no patients required conversion to open surgery. The proportion of patients with surgical-site infection did not differ between those who received PA 1 h before the start of surgery and every 3 h during surgery and those who received PA 1 h before the start of surgery, every 3 h during surgery, and twice a day for 24-72 h after surgery. CONCLUSION: Operative outcomes after LS improved after the standardization of the operative procedure. The administration of PA 1 h before surgery and every 3 h during surgery seems to be sufficient to prevent surgical-site infection during LS.

DOI： 10.1111/ases.12661

PubMed

待機的腹腔鏡下脾摘出術(LS)後の手術転帰を後ろ向きに検討した。2001～2015年に脾機能亢進症や脾臓腫瘍等に対し当該手術を施行された患者123例(男性48例、女性75例、平均59.5±11.8歳)を対象に、手術手技標準化前(初期)と標準化後(後期)の手術転帰と手術部位感染(SSI)に対する予防的抗生物質(PA)投与の影響について検討した。術後合併症は、創傷感染、門脈幹血栓症、膵瘻、胸水が各1例、術後出血が2例、腸損傷による再手術が1例であった。術後合併症は初期と後期で差は見られなかったが、術中出血量は後期で有意に少なかった。また後期では開腹術への移行例もなかった。SSIは、手術開始1時間前と術中3時間ごとにPA投与を行った群と、それに加え術後24～72時間に1日2回PA投与を行った群では差は見られなかった。LS後の成績は、術者の手技経験が増加すると共に改善した。また、術前1時間と術中3時間毎のPA投与はSSI予防に十分であることが示唆された。

2014年1月～2015年4月の間に、呼吸器感染症と診断された成人患者から収集した臨床分離菌1534株について、米国臨床検査標準委員会が推奨する手法を用いて、抗菌薬感受性試験を行った。その結果、1534株の内訳は、黄色ブドウ球菌(SA)335株、肺炎球菌(SP)264株、化膿連鎖球菌29株、インフルエンザ菌(HI)281株、Moraxella catarrhalis 164株、肺炎桿菌(KP)207株、緑膿菌(PA)254株であった。メチシリン耐性SAの割合は43.6%、ペニシリン感受性SPは100%で、HIの8.2%はβ-ラクタマーゼ産生アンピシリン耐性、49.1%はβ-ラクタマーゼ非産生アンピシリン耐性であった。拡大スペクトルβ-ラクタマーゼ産生KPとメタロβ-ラクタマーゼによる多剤耐性PAはそれぞれ9.2%と0.4%であった。

抗菌薬治療薬物血中濃度モニタリング(TDM)ガイドライン(GL)改訂版の発刊前後におけるバンコマイシン(VCM)投与の状況を把握するとともに、有効性と安全性について検討した。当院において2015年1月～2015年12月(GL改定前)、2017年1月～2017年12月(GL改定後)の期間においてVCMを3日間以上投与した症例を対象とした。患者数はGL改訂前が100例(男性68例、女性32例、平均63.3±15.2歳)、GL改訂後が162例(男性95例、女性67例、平均62.4±17.0歳)であった。eGFRが80～90mL/min/1.73m2では推奨投与量25mg/kg/日に対してGL改訂前は29.1mg/kg/日と多く、GL改訂後は23.7mg/kg/日と推奨投与量より少なかった。また、eGFRが60～80mL/min/1.73m2以下の層では、改訂版の推奨投与量よりもGL改訂前がすべて高い値を示していた。CRPはGL改訂前については投与前が10.1±8.2mg/dLから投与後が4.6±5.2mg/dL、GL改訂後では投与前が10.1±9.0mg/dLから投与後が4.2±4.8mg/dLへそれぞれ統計学的に有意に低下した。また、KDIGO診断基準に基づいて判定した結果、有意にGL改訂後のほうが急性腎障害の発生率が低かった。

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2019.08.018

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.diagmicrobio.2019.04.008

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2019.05.006

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

This study aimed to assess the predictive factors of bacteremia due to hypermucoviscous Klebsiella pneumoniae (hvKP), as well as the mortality. The medical records of 114 patients with K. pneumoniae bacteremia who were divided into the hvKP (n = 24) and non-hvKP (n = 90) groups and were retrospectively reviewed. The male-to-female ratio, age, and underlying disease did not differ between the 2 groups. Mortality was higher among patients in the hvKP bacteremia group than in the non-hvKP bacteremia group (29.2% vs 6.7%). Multivariate analysis showed that the independent predictors associated with hvKP bacteremia were abscess (P = 0.01) and no antibiotic exposure (P = 0.02); thus, early assessment of these conditions is important. For patients with a history of abscess and no antibiotic exposure, it is necessary to administer treatment while keeping the risk of hvKP in mind.

DOI： 10.1016/j.diagmicrobio.2019.04.008

PubMed

DOI： 10.1016/j.jiac.2019.05.006

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 49.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 9.2% and 0.4%, respectively.

DOI： 10.1016/j.jiac.2019.05.006

PubMed

DOI： 10.1016/j.jiac.2019.05.006

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ijantimicag.2019.05.018

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

A recent increase in the incidence of hypervirulent Klebsiella pneumoniae (hvKP) infections, especially those caused by a sublineage of clonal group CG23 (CG23-I), is raising serious health concerns worldwide. The high virulence of hvKP is, at least in part, attributed to the overproduction of capsular polysaccharide (CPS), which is triggered by a positive regulator of capsular polysaccharide synthesis (cps) genes, named rmpA (regulator of mucoid phenotype A). Although extensive research has been conducted on the mechanisms of hvKP virulence, no study has focused on the development of antivirulence therapeutics. This study attempted to identify and validate an antimicrobial agent able to suppress hvKP hypermucoviscosity. A total of 18 commercially available antimicrobial agents, including β-lactams, quinolones and aminoglycosides, were tested. Rifampicin (RFP) was found to have strong anti-mucoviscous activity against CG23-I hvKP even at subinhibitory concentrations. Polysaccharide extracts from hvKP showed substantially lowered viscosity when cells were grown with RFP. Moreover, microscopic observations demonstrated that RFP treatment results in a drastic reduction in the thickness of the CPS layer around hvKP cells. RFP treatment decreased transcript levels of rmpA and rmpA-regulated cps genes, indicating that RFP suppresses mucoviscosity of hvKP through inhibition of rmpA transcription. These data suggest that RFP may serve as a potential antivirulence agent for refractory hvKP infection.

DOI： 10.1016/j.ijantimicag.2019.05.018

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>The genus <i>Acinetobacter</i> comprises many species that can cause infectious diseases. Despite their importance as nosocomial pathogens, the clinical distributions of individual species or clones are not well understood. In this study, we aimed to characterize 13 <i>Acinetobacter</i> strains isolated from blood cultures from Osaka City University Hospital. We conducted whole-genome sequencing to reveal their genetic background. We also performed PCR-based open reading frame typing (POT) and compared the results with those of multilocus sequence typing (MLST) to confirm its reliability as a genotyping method. Although biochemical analysis suggested that most isolates were <i>A. baumannii</i>, genomic analysis revealed that the collection of <i>Acinetobacter</i> isolates comprised six different species, with non-<i>baumannii Acinetobacter</i> species representing the majority. All strains possessed an inherent ADC-type β-lactamase gene, whereas the distribution of OXA-type enzymes was limited to <i>A. baumannii, A. pittii</i>, and <i>A. colistiniresistens</i>. While MLST properly discriminated four <i>A. baumannii</i> strains as different clones, POT failed to distinguish three of the four <i>A. baumannii</i> strains from each other, highlighting a potential pitfall that may be encountered when applying POT to non-epidemiological <i>A. baumannii</i> strains.</p>

DOI： 10.7883/yoken.JJID.2018.403

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.diagmicrobio.2019.01.018

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

This study aimed to assess the prognostic factors of patients with bacteremia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) as well as the antimicrobial susceptibility, particularly to piperacillin/tazobactam (PTZ), among ESBL-PE strains. The medical records of 65 patients with ESBL-PE bacteremia divided into the survivor group (n = 52) and nonsurvivor group (n = 13) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, leukocyte count, C-reactive protein level, and treatment did not differ between the 2 groups. Multivariate analysis showed that the independent predictors associated with hospital mortality of ESBL-PE bacteremia were sepsis (P = 0.047) and febrile neutropenia (P = 0.008); thus, early assessment of these conditions is important. Further, the minimum inhibitory concentration values of ESBL-PE isolates in nonsurvivors tended to be higher than those in survivors. PTZ should be used with caution in cases of ESBL-PE strains with low susceptibility to the drug.

DOI： 10.1016/j.diagmicrobio.2019.01.018

PubMed

入院患者の血液培養から分離された13のAcinetobacter株の特徴を明らかにするめ、全ゲノム配列解析を行った。また、PCR-based open reading frame typing(POT)を用いて遺伝子型決定を行い、その結果を多座配列タイピング(MLST)の場合と比較して、POTの遺伝子型決定法としての信頼性を確かめた。その結果、生化学的解析でほとんどの分離株がAcinetobacter baumanniiであることが示唆された。一方、ゲノム解析では分離株は六つの異なる種で構成され、A.baumanniiではない種が大半を占めることが明らかになった。すべての株は固有のADC型β-ラクタマーゼ遺伝子を持っていたが、OXA型β-ラクタマーゼはA.baumannii、A.pittii、A.colistiniresistensにのみ分布していた。MLSTを用いた場合には四つのA.baumannii株を異なるクローンとして適切に判別できたが、POTを用いた場合には四つのA.baumannii株のうち三つを区別することができなかった。これらの結果から、本研究の条件においてはMLSTと比較してPOTの遺伝子型の判別能力は低いことが示された。

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2019.01.015

当院は2014年1月に抗真菌薬適正使用支援プログラム(AFSP)を開始した。本研究では2011年1月から2016年12月までに抗真菌薬の全身投与を受けた患者を登録し、AFSP介入前と介入後の群に分けた。抗真菌薬使用量(defined daily doses per 1000 patient-days)について群間に有意差はなかった。抗真菌薬投与日数(days of therapy per 1000 patient-days)は介入後に有意に低下した。抗真菌薬のコストは介入前の3年間と比べて介入後の3年間に260520ドル(13.5%)減少した。介入後にカンジダ血症患者の30日死亡率および院内死亡率は低下傾向を示した。AFSPは有効で費用対効果が高いアプローチであると考えられた。

DOI： 10.1016/j.jiac.2019.01.015

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0216956

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

ヒト血漿中のリネゾリド(LZD)とその代謝物PNU-142300およびPNU-142586を定量する超高速液体クロマトグラフ(UPLC)法を開発し、検証した。本手法ではヒト血漿試料をアセトニトリルで除蛋白した後、上清をACQUITY UPLC HSS T3カラムによる逆相クロマトグラフ法で分離・定量した。LZDの検量曲線の線形は0.2～50.0μg/mL(決定係数(r2)>0.9999)、PNU-142300とPNU-142586では0.2～20.0μg/mL(r2>0.9996と>0.9998)であった。また、上記3者のアッセイ内/アッセイ間の正確度(%)と精度(相対標準偏差、%)はFDAガイドラインの基準に合致していた。上記3者は血漿内で凍結融解3サイクルと、凍結血漿内で30日までの長期保存で安定しており、エキス内ではUPLC自動サンプラーにおいて4℃、48時間安定していた。以上より、LZD使用患者におけるLZD、PNU-142300およびPNU-142586の血漿濃度はこの手法で測定でき、LZD療法の最適化にて有用と考えられた。

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/cid/ciz287

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2018.10.016

PubMed

Publishing type：Research paper (scientific journal)  

41歳女。骨髄異形成症候群と診断されていた。自己末梢血幹細胞移植の施行19日後に発熱し、侵襲性肺アスペルギローシスと診断しボリコナゾール(VRCZ)による治療を開始した。確定診断のため、気管支鏡検査と気管支肺胞洗浄を行った。治療開始1ヵ月後でも患者の肺病変は変化なく、発熱も持続したため、抗菌薬をアンホテリシンBリポソーム製剤に切り替えたところ、副作用の嘔気が出現した。VRCZとカスポファンギン(CPFG)による併用療法を開始した結果、肺病変のサイズが徐々に減少した。気管支肺胞洗浄液から単離した糸状菌のβ-チューブリン遺伝子を、PCR産物からプライマー対を用いて直接配列決定し、Aspergillus felisとの100%の類似性を確認した。次いで実施した感受性試験の結果を基に、抗菌薬をVRCZ+CPFGからミカファンギンに変えると、5ヵ月間で治療が奏効した。

41歳女。骨髄異形成症候群と診断されていた。自己末梢血幹細胞移植の施行19日後に発熱し、侵襲性肺アスペルギローシスと診断しボリコナゾール(VRCZ)による治療を開始した。確定診断のため、気管支鏡検査と気管支肺胞洗浄を行った。治療開始1ヵ月後でも患者の肺病変は変化なく、発熱も持続したため、抗菌薬をアンホテリシンBリポソーム製剤に切り替えたところ、副作用の嘔気が出現した。VRCZとカスポファンギン(CPFG)による併用療法を開始した結果、肺病変のサイズが徐々に減少した。気管支肺胞洗浄液から単離した糸状菌のβ-チューブリン遺伝子を、PCR産物からプライマー対を用いて直接配列決定し、Aspergillus felisとの100%の類似性を確認した。次いで実施した感受性試験の結果を基に、抗菌薬をVRCZ+CPFGからミカファンギンに変えると、5ヵ月間で治療が奏効した。

DOI： 10.1016/j.jiac.2018.10.016

DOI： 10.1016/j.jiac.2018.10.016

PubMed

Publishing type：Research paper (scientific journal)  

Aspergillus species are a major cause of life-threatening infections in immunocompromised hosts, and the most common pathogen of invasive aspergillosis is Aspergillus fumigatus. Recently, the development of molecular identification has revealed cryptic Aspergillus species, and A. felis is one such species within the Aspergillus section Fumigati reported in 2013.We describe a case of invasive pulmonary aspergillosis caused by A. felis in a 41-year-old Japanese woman diagnosed with myelodysplastic syndrome. She presented with fever 19 days after undergoing autologous peripheral blood stem cell transplantation and was clinically diagnosed with invasive pulmonary aspergillosis. Bronchoscopy and bronchoalveolar lavage were performed for definitive diagnosis. The beta-tubulin genes of the mold isolated from the bronchoalveolar lavage fluid, and sequenced directly from the PCR products using a primer pair were found to have 100% homology with A. felis. We successfully treated the patient with echinocandin following careful susceptibility testing.To the best of our knowledge, this is the first published case reporting the clinical course for diagnosis and successful treatment of invasive aspergillosis by A. felis. (C) 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2018.10.016

PubMed

Publishing type：Research paper (scientific journal)  

<p>The genus <i>Acinetobacter</i> comprises many species that can cause infectious diseases. Despite their importance as nosocomial pathogens, the clinical distributions of individual species or clones are not well understood. In this study, we aimed to characterize 13 <i>Acinetobacter</i> strains isolated from blood cultures from Osaka City University Hospital. We conducted whole-genome sequencing to reveal their genetic background. We also performed PCR-based open reading frame typing (POT) and compared the results with those of multilocus sequence typing (MLST) to confirm its reliability as a genotyping method. Although biochemical analysis suggested that most isolates were <i>A. baumannii</i>, genomic analysis revealed that the collection of <i>Acinetobacter</i> isolates comprised six different species, with non-<i>baumannii Acinetobacter</i> species representing the majority. All strains possessed an inherent ADC-type β-lactamase gene, whereas the distribution of OXA-type enzymes was limited to <i>A. baumannii</i>, <i>A. pittii</i>, and <i>A. colistiniresistens</i>. While MLST properly discriminated four <i>A. baumannii</i> strains as different clones, POT failed to distinguish three out of the four <i>A. baumannii</i> strains from each other, highlighting a potential pitfall that may be encountered when applying POT to non-epidemiological <i>A. baumannii</i> strains.</p>

DOI： 10.7883/yoken.JJID.2018.403

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jiac.2019.01.015

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.

DOI： 10.1016/j.jiac.2019.01.015

PubMed

Publishing type：Research paper (scientific journal)  

<p>The Therapeutic Drug Monitoring (TDM) Guidelines for Antibiotics (the "Revised guidelines") were revised in June 2016. The Revised guidelines are followed to determine dosage and provide treatment at Osaka City University Hospital. The current study investigated VCM administration before and after the guidelines were revised as well as their effectiveness and safety. The period from January to December 2015 before the guidelines were revised ("before Revision") and the period from January to December 2017 after the guidelines were revised ("after Revision") were compared. One hundred and six patients received VCM therapy before Revision, and 184 received VCM therapy after Revision. Initially, 17.4％ of patients had the recommended serum VCM level of 10-15 µg/mL, but that increased to 41.7％ as a result of a pharmacist's involvement; 72.8％ of patients had serum VCM below 10 µg/mL after Revision. Acute kidney injury (AKI) was evaluated based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The incidence of AKI was 12.3％ before Revision and 5.4％ after Revision, so it was significantly lower before Revision. The 30-day survival rate was 94.6％ before Revision and 95.3％ after Revision, so the rate did not differ significantly.</p><p>When VCM therapy was administered in accordance with the Revised guidelines, the initial serum trough level of VCM was lower than 10 µg/mL in most patients, and VCM slightly affected the kidneys. Most patients had a serum VCM of 10-15 µg/mL as a result of a pharmacist's intervention, suggesting that the serum VCM level did not affect prognosis.</p>

DOI： 10.5649/jjphcs.45.576

CiNii Article

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.2169/naika.108.2268

CiNii Article

Publishing type：Research paper (scientific journal)  

<p>An ultra-performance liquid chromatography (UPLC) method was developed and validated for the quantification of linezolid, PNU-142300, and PNU-142586 in human plasma. After protein precipitation using acetonitrile, the protein-free supernatant was separated using reverse-phase chromatography using an ACQUITY UPLC HSS T3 column and monitored at 254 nm. <i>p</i>-Toluic acid was used as the internal standard. No interference peak was observed at the retention times of linezolid, PNU-142300, PNU-142586, and <i>p</i>-toluic acid from blank plasma. The calibration curve of linezolid was linear from 0.2 to 50.0 µg/mL (coefficient of determination (<i>r</i>²) > 0.9999) and those of PNU-142300 and PNU-142586 were linear from 0.2 to 20.0 µg/mL (<i>r</i>² > 0.9996 and > 0.9998, respectively). The intra- and inter-assay accuracy (%) and precision (relative standard deviation (RSD) %) of the three components were confirmed to meet the criteria of the U.S. Food and Drug Administration guidelines. Tests confirmed the stability of linezolid, PNU-142300, and PNU-142586 in plasma during three freeze-thaw cycles and long-term storage of frozen plasma for up to 30 d; in extracts they were stable in the UPLC autosampler for over 48 h at 4°C. Furthermore, plasma concentrations of linezolid, PNU-142300 and PNU-142586 in patients treated with linezolid could be measured using the UPLC method developed in this study. This assay would be a powerful tool for therapeutic drug monitoring and clinical pharmacokinetic/pharmacodynamic (PK/PD) analyses in the optimization of linezolid treatment.</p>

DOI： 10.1248/cpb.c18-00840

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>An ultra-performance liquid chromatography (UPLC) method was developed and validated for the quantification of linezolid, PNU-142300, and PNU-142586 in human plasma. After protein precipitation using acetonitrile, the protein-free supernatant was separated using reverse-phase chromatography using an ACQUITY UPLC HSS T3 column and monitored at 254 nm. <i>p</i>-Toluic acid was used as the internal standard. No interference peak was observed at the retention times of linezolid, PNU-142300, PNU-142586, and <i>p</i>-toluic acid from blank plasma. The calibration curve of linezolid was linear from 0.2 to 50.0 µg/mL (coefficient of determination (<i>r</i>²) > 0.9999) and those of PNU-142300 and PNU-142586 were linear from 0.2 to 20.0 µg/mL (<i>r</i>² > 0.9996 and > 0.9998, respectively). The intra- and inter-assay accuracy (%) and precision (relative standard deviation (RSD) %) of the three components were confirmed to meet the criteria of the U.S. Food and Drug Administration guidelines. Tests confirmed the stability of linezolid, PNU-142300, and PNU-142586 in plasma during three freeze-thaw cycles and long-term storage of frozen plasma for up to 30 d; in extracts they were stable in the UPLC autosampler for over 48 h at 4°C. Furthermore, plasma concentrations of linezolid, PNU-142300 and PNU-142586 in patients treated with linezolid could be measured using the UPLC method developed in this study. This assay would be a powerful tool for therapeutic drug monitoring and clinical pharmacokinetic/pharmacodynamic (PK/PD) analyses in the optimization of linezolid treatment.</p>

DOI： 10.1248/cpb.c18-00840

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. METHODS: This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. RESULTS: In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141-0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. CONCLUSION: Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.

DOI： 10.1371/journal.pone.0216956

PubMed

Publishing type：Research paper (scientific journal)  

Clostridioides difficileは有芽胞菌であり、乾燥環境でも長期生存可能であることから、医療関連感染症で重要である。また近年、欧米を中心に、第3の毒素であるbinary toxinを産生する高病原性株(BI/NAP1/027株)の出現と蔓延が問題となっている。今回、我々はA病棟でみられたbinary毒素産生株を含むクロストリデオイデス・ディフィシル感染症(Clostridioides difficile infection:CDI)の院内伝播をPCR-based Open-Reading-Flame Typing(POT)法を用いて遺伝子解析した。2017年1月から9月の期間、当院のA病棟で、入院中の患者から毒素陽性のC.difficileを9株(2株はbinary毒素陽性)検出した。その分離株をPOT法にて分子疫学解析したところbinary毒素陽性の2株とその他3株の遺伝子パターンがそれぞれ一致した。院内伝播の原因として、下痢回数が多く、便失禁をする患者がsuper-spreaderとなったことに加え、医療スタッフの手指衛生が十分でなかったことが要因と考えられた。その感染対策として、手指衛生の啓発活動、環境整備、病棟全体の塩素系消毒薬による清掃を実施して、院内伝播を終息することができたが、分子疫学解析を迅速に実施して正確な院内伝播を評価することが重要であり、今回の経験からCDIに対してもPOT法は有用性の高い分子疫学解析手法であると考えられた。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例1は39歳男性で、排便後に長さ約2mの白色紐状物を排泄したため当院感染症内科外来を受診した。虫卵検査の結果より裂頭条虫症と判断し、プラジカンテルを用いて駆虫した。駆虫後、長さ約5m、最大幅約8mmで正中に1列の生殖器を有する虫体を1隻排泄した。症例2は31歳女性で、排便後に長さ約20cmと約30cmの白色紐状物を排泄した。駆虫を希望し、当院感染症内科外来を受診した。虫体の写真より裂頭条虫症と判断した。患者の駆虫希望が強く、プラジカンテルを用いて駆虫を行ったが虫体は排泄されなかった。さらに、日本海裂頭条虫卵の発生実験を行ったところ、実験第34日にごく一部の虫卵内に6本の鉤を有するコラシジウムを確認した。実験第40日頃より小蓋が開き内部が空となった虫卵を散見したが、孵化したコラシジウムは確認できなかった。

Publishing type：Research paper (scientific journal)  

Clostridioides difficileは有芽胞菌であり、乾燥環境でも長期生存可能であることから、医療関連感染症で重要である。また近年、欧米を中心に、第3の毒素であるbinary toxinを産生する高病原性株(BI/NAP1/027株)の出現と蔓延が問題となっている。今回、我々はA病棟でみられたbinary毒素産生株を含むクロストリデオイデス・ディフィシル感染症(Clostridioides difficile infection:CDI)の院内伝播をPCR-based Open-Reading-Flame Typing(POT)法を用いて遺伝子解析した。2017年1月から9月の期間、当院のA病棟で、入院中の患者から毒素陽性のC.difficileを9株(2株はbinary毒素陽性)検出した。その分離株をPOT法にて分子疫学解析したところbinary毒素陽性の2株とその他3株の遺伝子パターンがそれぞれ一致した。院内伝播の原因として、下痢回数が多く、便失禁をする患者がsuper-spreaderとなったことに加え、医療スタッフの手指衛生が十分でなかったことが要因と考えられた。その感染対策として、手指衛生の啓発活動、環境整備、病棟全体の塩素系消毒薬による清掃を実施して、院内伝播を終息することができたが、分子疫学解析を迅速に実施して正確な院内伝播を評価することが重要であり、今回の経験からCDIに対してもPOT法は有用性の高い分子疫学解析手法であると考えられた。(著者抄録)

Publishing type：Research paper (scientific journal)  

症例1は39歳男性で、排便後に長さ約2mの白色紐状物を排泄したため当院感染症内科外来を受診した。虫卵検査の結果より裂頭条虫症と判断し、プラジカンテルを用いて駆虫した。駆虫後、長さ約5m、最大幅約8mmで正中に1列の生殖器を有する虫体を1隻排泄した。症例2は31歳女性で、排便後に長さ約20cmと約30cmの白色紐状物を排泄した。駆虫を希望し、当院感染症内科外来を受診した。虫体の写真より裂頭条虫症と判断した。患者の駆虫希望が強く、プラジカンテルを用いて駆虫を行ったが虫体は排泄されなかった。さらに、日本海裂頭条虫卵の発生実験を行ったところ、実験第34日にごく一部の虫卵内に6本の鉤を有するコラシジウムを確認した。実験第40日頃より小蓋が開き内部が空となった虫卵を散見したが、孵化したコラシジウムは確認できなかった。

Clostridioides difficileは有芽胞菌であり、乾燥環境でも長期生存可能であることから、医療関連感染症で重要である。また近年、欧米を中心に、第3の毒素であるbinary toxinを産生する高病原性株(BI/NAP1/027株)の出現と蔓延が問題となっている。今回、我々はA病棟でみられたbinary毒素産生株を含むクロストリデオイデス・ディフィシル感染症(Clostridioides difficile infection:CDI)の院内伝播をPCR-based Open-Reading-Flame Typing(POT)法を用いて遺伝子解析した。2017年1月から9月の期間、当院のA病棟で、入院中の患者から毒素陽性のC.difficileを9株(2株はbinary毒素陽性)検出した。その分離株をPOT法にて分子疫学解析したところbinary毒素陽性の2株とその他3株の遺伝子パターンがそれぞれ一致した。院内伝播の原因として、下痢回数が多く、便失禁をする患者がsuper-spreaderとなったことに加え、医療スタッフの手指衛生が十分でなかったことが要因と考えられた。その感染対策として、手指衛生の啓発活動、環境整備、病棟全体の塩素系消毒薬による清掃を実施して、院内伝播を終息することができたが、分子疫学解析を迅速に実施して正確な院内伝播を評価することが重要であり、今回の経験からCDIに対してもPOT法は有用性の高い分子疫学解析手法であると考えられた。(著者抄録)

Clostridioides difficileは有芽胞菌であり、乾燥環境でも長期生存可能であることから、医療関連感染症で重要である。また近年、欧米を中心に、第3の毒素であるbinary toxinを産生する高病原性株(BI/NAP1/027株)の出現と蔓延が問題となっている。今回、我々はA病棟でみられたbinary毒素産生株を含むクロストリデオイデス・ディフィシル感染症(Clostridioides difficile infection:CDI)の院内伝播をPCR-based Open-Reading-Flame Typing(POT)法を用いて遺伝子解析した。2017年1月から9月の期間、当院のA病棟で、入院中の患者から毒素陽性のC.difficileを9株(2株はbinary毒素陽性)検出した。その分離株をPOT法にて分子疫学解析したところbinary毒素陽性の2株とその他3株の遺伝子パターンがそれぞれ一致した。院内伝播の原因として、下痢回数が多く、便失禁をする患者がsuper-spreaderとなったことに加え、医療スタッフの手指衛生が十分でなかったことが要因と考えられた。その感染対策として、手指衛生の啓発活動、環境整備、病棟全体の塩素系消毒薬による清掃を実施して、院内伝播を終息することができたが、分子疫学解析を迅速に実施して正確な院内伝播を評価することが重要であり、今回の経験からCDIに対してもPOT法は有用性の高い分子疫学解析手法であると考えられた。(著者抄録)

症例1は39歳男性で、排便後に長さ約2mの白色紐状物を排泄したため当院感染症内科外来を受診した。虫卵検査の結果より裂頭条虫症と判断し、プラジカンテルを用いて駆虫した。駆虫後、長さ約5m、最大幅約8mmで正中に1列の生殖器を有する虫体を1隻排泄した。症例2は31歳女性で、排便後に長さ約20cmと約30cmの白色紐状物を排泄した。駆虫を希望し、当院感染症内科外来を受診した。虫体の写真より裂頭条虫症と判断した。患者の駆虫希望が強く、プラジカンテルを用いて駆虫を行ったが虫体は排泄されなかった。さらに、日本海裂頭条虫卵の発生実験を行ったところ、実験第34日にごく一部の虫卵内に6本の鉤を有するコラシジウムを確認した。実験第40日頃より小蓋が開き内部が空となった虫卵を散見したが、孵化したコラシジウムは確認できなかった。

症例1は39歳男性で、排便後に長さ約2mの白色紐状物を排泄したため当院感染症内科外来を受診した。虫卵検査の結果より裂頭条虫症と判断し、プラジカンテルを用いて駆虫した。駆虫後、長さ約5m、最大幅約8mmで正中に1列の生殖器を有する虫体を1隻排泄した。症例2は31歳女性で、排便後に長さ約20cmと約30cmの白色紐状物を排泄した。駆虫を希望し、当院感染症内科外来を受診した。虫体の写真より裂頭条虫症と判断した。患者の駆虫希望が強く、プラジカンテルを用いて駆虫を行ったが虫体は排泄されなかった。さらに、日本海裂頭条虫卵の発生実験を行ったところ、実験第34日にごく一部の虫卵内に6本の鉤を有するコラシジウムを確認した。実験第40日頃より小蓋が開き内部が空となった虫卵を散見したが、孵化したコラシジウムは確認できなかった。

Publishing type：Research paper (scientific journal)  

DOI： 10.1111/ases.12661

PubMed

Publishing type：Research paper (scientific journal)  

バンコマイシン塩酸塩(vancomycin:以下、VCM)は、治療薬物モニタリング(therapeutic drug monitoring:以下、TDM)が治療効果と副作用防止につながる。今回、病棟専任薬剤師の介入によるVCMの急性腎障害発現への影響について検討を行った。VCMが投与された症例を病棟薬剤業務開始前(before inpatient pharmaceutical services:before IPS)群と、病棟薬剤業務開始後(after inpatient pharmaceutical services:以下、after IPS)群に分類した。after IPS群で、TDM実施率が有意に上昇し(p<0.001)、また、中毒域到達率が有意に低下し(p=0.029)、VCMによる急性腎障害発現率は有意に減少した(p=0.039)。これらの結果より、病棟専任薬剤師による介入は、VCMの急性腎障害を減少する可能性が示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

バンコマイシン塩酸塩(vancomycin:以下、VCM)は、治療薬物モニタリング(therapeutic drug monitoring:以下、TDM)が治療効果と副作用防止につながる。今回、病棟専任薬剤師の介入によるVCMの急性腎障害発現への影響について検討を行った。VCMが投与された症例を病棟薬剤業務開始前(before inpatient pharmaceutical services:before IPS)群と、病棟薬剤業務開始後(after inpatient pharmaceutical services:以下、after IPS)群に分類した。after IPS群で、TDM実施率が有意に上昇し(p<0.001)、また、中毒域到達率が有意に低下し(p=0.029)、VCMによる急性腎障害発現率は有意に減少した(p=0.039)。これらの結果より、病棟専任薬剤師による介入は、VCMの急性腎障害を減少する可能性が示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

バンコマイシン塩酸塩(vancomycin:以下、VCM)は、治療薬物モニタリング(therapeutic drug monitoring:以下、TDM)が治療効果と副作用防止につながる。今回、病棟専任薬剤師の介入によるVCMの急性腎障害発現への影響について検討を行った。VCMが投与された症例を病棟薬剤業務開始前(before inpatient pharmaceutical services:before IPS)群と、病棟薬剤業務開始後(after inpatient pharmaceutical services:以下、after IPS)群に分類した。after IPS群で、TDM実施率が有意に上昇し(p<0.001)、また、中毒域到達率が有意に低下し(p=0.029)、VCMによる急性腎障害発現率は有意に減少した(p=0.039)。これらの結果より、病棟専任薬剤師による介入は、VCMの急性腎障害を減少する可能性が示唆された。(著者抄録)

バンコマイシン塩酸塩(vancomycin:以下、VCM)は、治療薬物モニタリング(therapeutic drug monitoring:以下、TDM)が治療効果と副作用防止につながる。今回、病棟専任薬剤師の介入によるVCMの急性腎障害発現への影響について検討を行った。VCMが投与された症例を病棟薬剤業務開始前(before inpatient pharmaceutical services:before IPS)群と、病棟薬剤業務開始後(after inpatient pharmaceutical services:以下、after IPS)群に分類した。after IPS群で、TDM実施率が有意に上昇し(p<0.001)、また、中毒域到達率が有意に低下し(p=0.029)、VCMによる急性腎障害発現率は有意に減少した(p=0.039)。これらの結果より、病棟専任薬剤師による介入は、VCMの急性腎障害を減少する可能性が示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p>A 53-year-old woman was hospitalized due to septic shock after developing pneumococcal pneumonia after undergoing esophageal cancer surgery. Her transverse colon became perforated after receiving antimicrobial chemotherapy; therefore, emergency subtotal colectomy was performed. Fungi detected in both her colon tissue and a drainage sample indicated intestinal mucormycosis. Early intensive treatment with high-dose liposomal amphotericin B was successful, and she was subsequently discharged from the hospital. The fungal isolates were identified to be <i>Lichtheimia ramosa</i> and <i>Aspergillus calidoustus</i> via gene sequencing using panfungal primers as well as species-specific primers against elongation factor 1 and beta-tubulin for detecting <i>Lichtheimia</i> and <i>Aspergillus</i>, respectively. </p>

DOI： 10.2169/internalmedicine.0254-17

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

症例は53歳女性で、肺炎球菌性肺炎を発症後の敗血症性ショックにより来院した。2.5年前に食道癌手術を施行されていた。血液培養でペニシリン感受性Streptococcus pneumoniaeが検出され、人工呼吸器装着下でメロペネム、免疫グロブリン、ヒドロコルチゾンを7日間投与し、持続血液濾過透析を行った。12日目の腹部X線検査とCT検査で腹腔のフリーエアーが判明し、横行結腸穿孔に対して緊急結腸亜全摘術を行った。術後に発熱と重度炎症が持続し、大腸内視鏡検査で残存直腸に複数の潰瘍と出血が確認された。結腸組織とドレナージ標本から真菌が検出され、ムコール症が示唆された。高用量リポソーマルアムホテリシンBの投与を開始すると解熱し、ドレナージ液から糸状菌が検出されなくなり、炎症反応が消失した。分離真菌は、Lichtheimia ramosaおよびAspergillus calidoustusと特定された。

症例は53歳女性で、肺炎球菌性肺炎を発症後の敗血症性ショックにより来院した。2.5年前に食道癌手術を施行されていた。血液培養でペニシリン感受性Streptococcus pneumoniaeが検出され、人工呼吸器装着下でメロペネム、免疫グロブリン、ヒドロコルチゾンを7日間投与し、持続血液濾過透析を行った。12日目の腹部X線検査とCT検査で腹腔のフリーエアーが判明し、横行結腸穿孔に対して緊急結腸亜全摘術を行った。術後に発熱と重度炎症が持続し、大腸内視鏡検査で残存直腸に複数の潰瘍と出血が確認された。結腸組織とドレナージ標本から真菌が検出され、ムコール症が示唆された。高用量リポソーマルアムホテリシンBの投与を開始すると解熱し、ドレナージ液から糸状菌が検出されなくなり、炎症反応が消失した。分離真菌は、Lichtheimia ramosaおよびAspergillus calidoustusと特定された。

Publishing type：Research paper (scientific journal)  

発熱性好中球減少症(FN:febrile neutropenia)治療において薬剤耐性グラム陽性菌感染が疑われる状況下等では抗methicillin-resistant Staphylococcus aureus(MRSA)薬としてグリコペプチド系抗菌薬(GPs)の使用が推奨されている。しかしながら、GPs継続不可時のFNに対する2次治療として、daptomycin(DAP)やlinezolid(LZD)の有効性を検討した報告はない。そこで今回、GPs不応性のFNに対する2次治療薬としてDAPとLZDの有効性と安全性について比較検討した。2010年1月から2016年12月の期間に大阪市立大学医学部附属病院でFN治療に対してGPsが投与された患者のうち、効果不十分等の理由でDAPまたはLZDによる2次治療が実施された症例を対象とした。診療録より患者背景、臨床検査値、バイタルサインの推移、解熱効果、投与終了30日後の生存率、臨床効果、細菌学的効果について後方視的に調査した。対象症例は、DAP群20例、LZD群13例であり、患者背景、投与期間、前治療で使用されたGPsおよび投与期間に有意差は認められなかった。両群とも投与終了時の臨床効果や投与終了30日後の生存率に両群間で有意差は認めなかったが、投与開始後4日目までの解熱効果がLZD群で有効率81.8%とDAP群の有効率31.3%と比較して有意に高いことが確認された。有害事象が原因による投与中止例が両群とも1例ずつに認められたが、いずれも軽微で重篤な副作用は確認されなかった。本検討からGPsの継続が困難なFN症例に対してLZDおよびDAPはどちらも治療選択肢の一つとしてなりえる可能性がある。特にLZDにはFNのような好中球数の減少した病態に対しても抗炎症作用が発揮され、早期の解熱効果が得られると考えられる。(著者抄録)

発熱性好中球減少症(FN:febrile neutropenia)治療において薬剤耐性グラム陽性菌感染が疑われる状況下等では抗methicillin-resistant Staphylococcus aureus(MRSA)薬としてグリコペプチド系抗菌薬(GPs)の使用が推奨されている。しかしながら、GPs継続不可時のFNに対する2次治療として、daptomycin(DAP)やlinezolid(LZD)の有効性を検討した報告はない。そこで今回、GPs不応性のFNに対する2次治療薬としてDAPとLZDの有効性と安全性について比較検討した。2010年1月から2016年12月の期間に大阪市立大学医学部附属病院でFN治療に対してGPsが投与された患者のうち、効果不十分等の理由でDAPまたはLZDによる2次治療が実施された症例を対象とした。診療録より患者背景、臨床検査値、バイタルサインの推移、解熱効果、投与終了30日後の生存率、臨床効果、細菌学的効果について後方視的に調査した。対象症例は、DAP群20例、LZD群13例であり、患者背景、投与期間、前治療で使用されたGPsおよび投与期間に有意差は認められなかった。両群とも投与終了時の臨床効果や投与終了30日後の生存率に両群間で有意差は認めなかったが、投与開始後4日目までの解熱効果がLZD群で有効率81.8%とDAP群の有効率31.3%と比較して有意に高いことが確認された。有害事象が原因による投与中止例が両群とも1例ずつに認められたが、いずれも軽微で重篤な副作用は確認されなかった。本検討からGPsの継続が困難なFN症例に対してLZDおよびDAPはどちらも治療選択肢の一つとしてなりえる可能性がある。特にLZDにはFNのような好中球数の減少した病態に対しても抗炎症作用が発揮され、早期の解熱効果が得られると考えられる。(著者抄録)

DOI： 10.34426/j03177.2018256916

DOI： 10.7883/yoken.JJID.2017.082

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.2169/naika.107.416

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.2169/internalmedicine.0254-17

PubMed

Publishing type：Research paper (scientific journal)  

症例は47歳女性で、肛門からproglottidsが排出され、下腹部に不快感があった。患者は約10ヵ月前にフィリピンに1ヵ月間滞在し、生のブタ肝臓を食していた。触知腹部腫瘍や腹部圧痛は観察されず、身体検査は正常であった。血液検査、その他検査結果は正常範囲内であった。proglottidsの所見、臨床データ、食事歴からTaenia saginataまたはT.asiatica感染が疑われた。プラジカンテル600mg/日と下剤を投与し、多くのproglottidsと寄生虫の頭節が排出され、駆虫に成功した。多重PCRによってT.asiaticaと同定した。食事歴を調査したところ、日本では通常は肉を焼いて食べ、生では食べないことから、最終的に輸入T.asiatica感染症と診断した。

Publishing type：Research paper (scientific journal)  

慢性肺アスペルギルス症(CPA)に対するアムホテリシンBリポソーム製剤(L-AMB)静注(2.5〜5.0mg/kg、1日1回)とボリコナゾール(VRCZ)静注(Day1は6mg/kgを2回、その後は4mg/kgを1日2回)を比較する多施設共同無作為化非盲検試験を実施した。CPA患者166例をL-AMB群83例(男性74.7%、中央値72.0歳)とVRCZ群83例(男性83.1%、中央値71.0歳)に無作為に割り付け、投与2週後および投与終了時に有効性を評価した。L-AMB群の51例とVRCZ群の59例をプロトコルの適合集団として解析した。その結果、L-AMB群とVRCZ群における2週後の有効率はそれぞれ49.0%と59.3%、治療終了時の有効率はそれぞれ52.9%と67.8%で、両群間で有意差はみられなかった。L-AMB群とVRCZ群における副作用の発生率はそれぞれ54.2と59.0%であり、有意差はみられなかった。以上から、CPAに対してL-AMBはVRCZと同程度に有効であり、副作用の発生率にも差はみられないことが示された。

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

Publishing type：Research paper (scientific journal)  

症例は47歳女性で、肛門からproglottidsが排出され、下腹部に不快感があった。患者は約10ヵ月前にフィリピンに1ヵ月間滞在し、生のブタ肝臓を食していた。触知腹部腫瘍や腹部圧痛は観察されず、身体検査は正常であった。血液検査、その他検査結果は正常範囲内であった。proglottidsの所見、臨床データ、食事歴からTaenia saginataまたはT.asiatica感染が疑われた。プラジカンテル600mg/日と下剤を投与し、多くのproglottidsと寄生虫の頭節が排出され、駆虫に成功した。多重PCRによってT.asiaticaと同定した。食事歴を調査したところ、日本では通常は肉を焼いて食べ、生では食べないことから、最終的に輸入T.asiatica感染症と診断した。

慢性肺アスペルギルス症(CPA)に対するアムホテリシンBリポソーム製剤(L-AMB)静注(2.5～5.0mg/kg、1日1回)とボリコナゾール(VRCZ)静注(Day1は6mg/kgを2回、その後は4mg/kgを1日2回)を比較する多施設共同無作為化非盲検試験を実施した。CPA患者166例をL-AMB群83例(男性74.7%、中央値72.0歳)とVRCZ群83例(男性83.1%、中央値71.0歳)に無作為に割り付け、投与2週後および投与終了時に有効性を評価した。L-AMB群の51例とVRCZ群の59例をプロトコルの適合集団として解析した。その結果、L-AMB群とVRCZ群における2週後の有効率はそれぞれ49.0%と59.3%、治療終了時の有効率はそれぞれ52.9%と67.8%で、両群間で有意差はみられなかった。L-AMB群とVRCZ群における副作用の発生率はそれぞれ54.2と59.0%であり、有意差はみられなかった。以上から、CPAに対してL-AMBはVRCZと同程度に有効であり、副作用の発生率にも差はみられないことが示された。

Publishing type：Research paper (scientific journal)  

DOI： 10.7883/yoken.JJID.2017.082

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.7883/yoken.JJID.2017.082

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

大学病院10施設から収集した2003〜2014年までのデータから、カンジダ血症および起因菌Candida種の後ろ向き疫学調査を実施した。なお、本調査では、血液培養検査検体計328318個を用いて行った。その結果、全検体に対する陽性率は13.0±0.52%で、真菌の存在率は、全検体に対して0.58±0.09%、陽性検体に対して4.46±0.66%であった。また、検体から1921株のCandida属菌が同定され、最も多く認められた菌種がC.albicans(39.5%)で、続いて、C.parapsilosis(23.3%)、C.glabrata(13.2%)、C.tropicalis(7.1%)、C.krusei(3.2%)の順に多く認められた。特にC.albicansは試験期間の前半の方が後半よりも高い存在割合が示され、C.glabrataでは試験期間の前半の方が後半よりも低く、C.kruseiでは、試験期間の前半の方が、後半よりも高い存在割合が示された。

大学病院10施設から収集した2003～2014年までのデータから、カンジダ血症および起因菌Candida種の後ろ向き疫学調査を実施した。なお、本調査では、血液培養検査検体計328318個を用いて行った。その結果、全検体に対する陽性率は13.0±0.52%で、真菌の存在率は、全検体に対して0.58±0.09%、陽性検体に対して4.46±0.66%であった。また、検体から1921株のCandida属菌が同定され、最も多く認められた菌種がC.albicans(39.5%)で、続いて、C.parapsilosis(23.3%)、C.glabrata(13.2%)、C.tropicalis(7.1%)、C.krusei(3.2%)の順に多く認められた。特にC.albicansは試験期間の前半の方が後半よりも高い存在割合が示され、C.glabrataでは試験期間の前半の方が後半よりも低く、C.kruseiでは、試験期間の前半の方が、後半よりも高い存在割合が示された。

Publishing type：Research paper (scientific journal)  

DOI： 10.3314/mmj.17-00014

PubMed

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.59.Suppl1.0_64

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.11534/jsmm.59.Suppl1.0_51_2

CiNii Article

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.59.Suppl1.0_49_2

CiNii Article

Publishing type：Research paper (scientific journal)  

Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to infection of Aspergillus spp. We conducted a randomized, multicenter, open-label trial comparing intravenous liposomal amphotericin B (L-AMB) of 2.5-5.0 mg/kg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily. Treatment effectiveness was defined by clinical, and radiological improvement at both 2 weeks after the initial administration and at the end of therapy. The total of 166 patients were recruited and 83 patients for each drug group were assigned. Total of 51 and 59 cases of L-AMB and VRCZ, respectively were assessed as per-protocol populations. The difference in efficacy rates between L-AMB and VRCZ was not significant, either after 2 weeks [49.0% vs. 59.3%; the absolute difference, 10.3% with a 95% confidence interval (CI), -8.4 to 29.00, P=0.279] or at the end of therapy (52.9% vs. 67.8%; the absolute difference, 14.9% with a 95% CI, -3.4 to 33.2, P=0.111). In the safety evaluation, no statistical difference of occurrence rates in both LAMB and VRCZ group (54.2% vs. 59.0%, P=0.531). L-AMB was as effective as VRCZ with no significant difference of adverse effects in the treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000002236.)

DOI： 10.11343/amn.61.167

CiNii Article

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.2169/naika.107.416

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

The Epidemiological Investigation Committee for Human Mycoses in Japan performed a retrospective epidemiological survey of candidemia and causative <I>Candida</I> species. Data from 2003 to 2014 were collected from 10 Japanese university hospitals. A total of 328,318 blood cultures were included. The prevalence of fungi in all cultures and in positive cultures were 0.58±0.09% and 4.46±0.66%, respectively. Among the results that were positive for <I>Candida</I> species (N=1,921), <I>Candida albicans</I> was the most common species (39.5%) and was followed by <I>Candida parapsilosis</I> (23.3%), <I>Candida glabrata</I> (13.2%), <I>Candida tropicalis</I> (7.1%), <I>Candida krusei</I> (3.2%), and others (13.7%). During the last 6 years, the frequency of <I>C. albicans</I> has significantly decreased in Japan, while that of <I>C. glabrata</I> has increased. Additional surveys are needed to continuously monitor the trends in the distribution of candidemia.

DOI： 10.3314/mmj.17-00014

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.11534/jsmm.59.suppl1.0_64

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.11534/jsmm.59.suppl1.0_51_2

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.11534/jsmm.59.suppl1.0_49_2

CiNii Article

Chronic pulmonary aspergillosis (CPA) is slowly progressive inflammatory pulmonary syndrome due to infection of Aspergillus spp. We conducted a randomized, multicenter, open-label trial comparing intravenous liposomal amphotericin B (L-AMB) of 2.5-5.0 mg/kg once daily with intravenous voriconazole (VRCZ) of 6 mg/kg twice on Day 1 followed by 4 mg/kg twice daily. Treatment effectiveness was defined by clinical, and radiological improvement at both 2 weeks after the initial administration and at the end of therapy. The total of 166 patients were recruited and 83 patients for each drug group were assigned. Total of 51 and 59 cases of L-AMB and VRCZ, respectively were assessed as per-protocol populations. The difference in efficacy rates between L-AMB and VRCZ was not significant, either after 2 weeks [49.0% vs. 59.3%; the absolute difference, 10.3% with a 95% confidence interval (CI), -8.4 to 29.00, P=0.279] or at the end of therapy (52.9% vs. 67.8%; the absolute difference, 14.9% with a 95% CI, -3.4 to 33.2, P=0.111). In the safety evaluation, no statistical difference of occurrence rates in both LAMB and VRCZ group (54.2% vs. 59.0%, P=0.531). L-AMB was as effective as VRCZ with no significant difference of adverse effects in the treatment of CPA. (UMIN Clinical Trials Registry number, UMIN000002236.)

DOI： 10.11343/amn.61.167

CiNii Article

DOI： 10.7883/yoken.jjid.2017.082

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/cid/cix579

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/cid/cix579

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

3次医療機関におけるバンコマイシン感受性Enterococcus faecalis菌血症患者60名(男38名、女22名、平均62.0歳)及びE.faecium菌血症患者48名(男29名、女19名、平均59.1歳)の臨床的特徴を挙げ、感染、予後、分離株薬剤感受性の予測因子を調べた。その結果、E.faecalis菌血症患者のうち、血液悪性腫瘍9名を含む悪性腫瘍29名、心血管疾患19名、キノロン系抗菌薬投与12名、院内感染48名であった。E.faecium菌血症患者のうち、血液悪性腫瘍21名を含む悪性腫瘍患者40名、心血管疾患4名、キノロン系抗菌薬投与24名、院内感染46名であった。E.faecium菌血症での好中球減少症は35.4%で、E.faecalis菌血症での10.0%よりも有意に高かった。E.faecalis菌血症の治療は、ペニシリン抗菌薬投与が25名で、根治療法として18名に抗MRSA薬を投与した。E.faecium菌血症では、37名に抗MRSA薬を投与した。多変量解析にてE.faecium菌血症の独立予測因子はキノロン系抗菌薬使用、悪性腫瘍、長期入院で、心血管疾患は逆の予測因子であった。抗菌薬感受性に関しては、E.faecium分離株のダプトマイシン低感受性(MIC≧3μg/mL)菌の割合が8.5%とE.faecalisの0%よりも高かった。

Publishing type：Research paper (scientific journal)  

<p><i>Enterococcus faecium</i> has high levels of resistance to multiple antibiotics, and the mortality due to <i>E. faecium</i> bacteremia is high. Accordingly, <i>E. faecium</i> strains with low susceptibility to daptomycin are a concern in clinical practice. This study assessed the predictive factors and prognosis of patients with bacteremia due to<i> E. faecium</i> as well as the antimicrobial susceptibility, particularly to daptomycin, among <i>E. faecium</i> isolates. The medical records of patients admitted to Osaka City University Hospital with <i>E. faecalis</i> (n = 60) and <i>E. faecium</i> (n = 48) bacteremia between January 2011 and March 2016 were retrospectively reviewed. The <i>E. faecalis</i> group (mean age: 62.0 years) included 22 women, and the <i>E. faecium</i> group (mean age: 59.1 years) included 19 women. Predictive factors for infection, prognosis, and isolate antimicrobial susceptibilities were evaluated. The mean Sequential Organ Failure Assessment score and mortality rate did not differ between the two groups. The independent predictors of <i>E. faecium</i> bacteremia in multivariate analysis included quinolone use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p = 0.016). Cardiovascular disease was associated with a reduced risk of <i>E. faecium</i> bacteremia (p = 0.015). Notably, the percentage of <i>E. faecium</i> isolates with low daptomycin susceptibility was higher than that of <i>E. faecalis</i> (8.5% vs. 0%, p = 0.036). Thus, <i>E. faecium</i> should be considered when administering antibiotic therapy to patients with a history of these predictors. Furthermore, the use of daptomycin should be avoided in case of <i>E. faecium</i> with low susceptibility to daptomycin.</p>

DOI： 10.1620/tjem.243.211

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p><i>Enterococcus faecium</i> has high levels of resistance to multiple antibiotics, and the mortality due to <i>E. faecium</i> bacteremia is high. Accordingly, <i>E. faecium</i> strains with low susceptibility to daptomycin are a concern in clinical practice. This study assessed the predictive factors and prognosis of patients with bacteremia due to<i> E. faecium</i> as well as the antimicrobial susceptibility, particularly to daptomycin, among <i>E. faecium</i> isolates. The medical records of patients admitted to Osaka City University Hospital with <i>E. faecalis</i> (n = 60) and <i>E. faecium</i> (n = 48) bacteremia between January 2011 and March 2016 were retrospectively reviewed. The <i>E. faecalis</i> group (mean age: 62.0 years) included 22 women, and the <i>E. faecium</i> group (mean age: 59.1 years) included 19 women. Predictive factors for infection, prognosis, and isolate antimicrobial susceptibilities were evaluated. The mean Sequential Organ Failure Assessment score and mortality rate did not differ between the two groups. The independent predictors of <i>E. faecium</i> bacteremia in multivariate analysis included quinolone use (p = 0.025), malignancy (p = 0.021), and prolonged hospitalization (p = 0.016). Cardiovascular disease was associated with a reduced risk of <i>E. faecium</i> bacteremia (p = 0.015). Notably, the percentage of <i>E. faecium</i> isolates with low daptomycin susceptibility was higher than that of <i>E. faecalis</i> (8.5% vs. 0%, p = 0.036). Thus, <i>E. faecium</i> should be considered when administering antibiotic therapy to patients with a history of these predictors. Furthermore, the use of daptomycin should be avoided in case of <i>E. faecium</i> with low susceptibility to daptomycin.</p>

DOI： 10.1620/tjem.243.211

PubMed

CiNii Article

3次医療機関におけるバンコマイシン感受性Enterococcus faecalis菌血症患者60名(男38名、女22名、平均62.0歳)及びE.faecium菌血症患者48名(男29名、女19名、平均59.1歳)の臨床的特徴を挙げ、感染、予後、分離株薬剤感受性の予測因子を調べた。その結果、E.faecalis菌血症患者のうち、血液悪性腫瘍9名を含む悪性腫瘍29名、心血管疾患19名、キノロン系抗菌薬投与12名、院内感染48名であった。E.faecium菌血症患者のうち、血液悪性腫瘍21名を含む悪性腫瘍患者40名、心血管疾患4名、キノロン系抗菌薬投与24名、院内感染46名であった。E.faecium菌血症での好中球減少症は35.4%で、E.faecalis菌血症での10.0%よりも有意に高かった。E.faecalis菌血症の治療は、ペニシリン抗菌薬投与が25名で、根治療法として18名に抗MRSA薬を投与した。E.faecium菌血症では、37名に抗MRSA薬を投与した。多変量解析にてE.faecium菌血症の独立予測因子はキノロン系抗菌薬使用、悪性腫瘍、長期入院で、心血管疾患は逆の予測因子であった。抗菌薬感受性に関しては、E.faecium分離株のダプトマイシン低感受性(MIC≧3μg/mL)菌の割合が8.5%とE.faecalisの0%よりも高かった。

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Mucormycosis is the second most common mould infection, often indistinguishable from other invasive mould infections such as aspergillosis. Although an appropriate antifungal therapy is effective at an early stage of the infection, there is no reliable diagnostic method for decision making. Thus, it is necessary to develop an efficient method that can detect mucormycosis rapidly and accurately. We searched for secreted or membrane-bound proteins of Rhizopus oryzae, which is the most common pathogen of mucormycosis, using the method of a signal sequence trap by retrovirus-mediated expression (SST-REX). Among the identified proteins, a Rhizopus-specific antigen was selected as a candidate, and efficacy of this specific antigen was evaluated using R. oryzae-infected mice. Of 302 clones obtained from the SST-REX library, a hypothetical protein (23 kDa, named "protein RSA") was selected as a candidate because of its highest prevalence of clones. Protein RSA was detected at significantly higher concentrations in serum and in lung homogenates of the infected mice as compared to those of uninfected mice. Our study indicates that protein RSA may be a promising biomarker of R. oryzae infection. SST-REX may be useful for comprehensive screening of prospective eukaryotic biomarkers of intractable mould infections.

DOI： 10.1093/mmy/myw146

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/mmy/myw146

PubMed

＜Point＞侵襲性肺アスペルギルス症の第一選択薬はボリコナゾール(VRCZ)である.アムホテリシンBリポソーム製剤(L-AMB)は同等,もしくはその代替薬として位置付けられる.キャンディン系薬のミカファンギン(MCFG)やカスポファンギン(CPFG),アゾール系のイトリゾール(ITCZ)は第二選択薬に位置付けられる.また,キャンディン系薬は重症・難治例に対する併用療法の一翼を担う薬剤である.(著者抄録)

DOI： 10.11477/mf.1437200064

Other URL： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J06862&link_issn=&doc_id=20170814310017&doc_link_id=10.11477%2Fmf.1437200064&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1437200064&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Publishing type：Research paper (scientific journal)  

ESBL産生大腸菌による菌血症患者31例(男性12例、女性19例、平均62.5±18.9歳)、非ESBL大腸菌による菌血症患者98例(男性46例、女性52例、平均67.6±13.9歳)を対象に、菌血症発症の危険因子と予後について検討した。白血球数、CRPのような臨床検査値の測定を行い、臨床分離菌の検出を実施した。抗菌薬は菌血症発症の5日以内に経験的治療を開始した後に根治治療を行った。その結果、抗菌薬感受性に関して、ESBL大腸菌はレボフロキサシン、ゲンタマイシン、スルファメトキサゾール/トリメトプリムへの感受性が有意に低かった。投与した抗菌薬ではカルバペネム系が多く、ESBL菌血症群では18例(58.1%)がカルバペネムまたはタゾバクタム/ピペラシリンを投与されていた。危険因子について検討した単変量解析では、男女比、平均年齢、基礎疾患、白血球数、CRP値、SOFAスコアに群間差は認められなかった。多変量解析では、菌分離前の免疫抑制剤またはコルチコステロイド、キノロン投与がESBL大腸菌菌血症の発症の独立予測因子であることが示された。ESBL大腸菌菌血症患者のうち、9例にカルバペネム、4例にタゾバクタム/ピペラシリン、2例にセフメタゾールが投与されており、患者背景と死亡率に群間差はみられなかった。免疫抑制剤、コルチコステロイド、キノロンの投与によって、ESBL産生大腸菌による菌血症のリスクが高まる可能性が示された。

ESBL産生大腸菌による菌血症患者31例(男性12例、女性19例、平均62.5±18.9歳)、非ESBL大腸菌による菌血症患者98例(男性46例、女性52例、平均67.6±13.9歳)を対象に、菌血症発症の危険因子と予後について検討した。白血球数、CRPのような臨床検査値の測定を行い、臨床分離菌の検出を実施した。抗菌薬は菌血症発症の5日以内に経験的治療を開始した後に根治治療を行った。その結果、抗菌薬感受性に関して、ESBL大腸菌はレボフロキサシン、ゲンタマイシン、スルファメトキサゾール/トリメトプリムへの感受性が有意に低かった。投与した抗菌薬ではカルバペネム系が多く、ESBL菌血症群では18例(58.1%)がカルバペネムまたはタゾバクタム/ピペラシリンを投与されていた。危険因子について検討した単変量解析では、男女比、平均年齢、基礎疾患、白血球数、CRP値、SOFAスコアに群間差は認められなかった。多変量解析では、菌分離前の免疫抑制剤またはコルチコステロイド、キノロン投与がESBL大腸菌菌血症の発症の独立予測因子であることが示された。ESBL大腸菌菌血症患者のうち、9例にカルバペネム、4例にタゾバクタム/ピペラシリン、2例にセフメタゾールが投与されており、患者背景と死亡率に群間差はみられなかった。免疫抑制剤、コルチコステロイド、キノロンの投与によって、ESBL産生大腸菌による菌血症のリスクが高まる可能性が示された。

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo.
Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time-kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2 h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection.
Results: The MIC range, MIC50, MIC90 and geometric mean MIC of T-2307 were 0.0078-0.0625, 0.0313, 0.0625 and 0.0394 mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2 mg/kg/day, amphotericin B at 1 mg/kg/day and fluconazole at 160 mg/kg/day from 2 h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1 mg/kg/day.
Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.

DOI： 10.1093/jac/dkx020

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jac/dkx020

PubMed

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

当院に感染症コントロールチームが設置される前の2007年1月～2013年3月に多剤耐性緑膿菌(MDRP)株が分離された患者40例(男性28例、女性12例、平均64.3歳)の診療録を後向きに評価し、患者背景、重症度、予後、抗生物質感受性を調べた。MDRP株数は、2010年が12株、2012年が13株、2013年が4株であった。22例(55.0%)が同一病棟に入院していた。分離頻度が最も高かった検体は喀痰であった(23例、57.5%)。11例が悪性腫瘍、10例が創傷を有していた。大半の患者で機能状態(PS)は非常に低く、70.0%がPS 4、15.0%がPS 3であった。19例(47.5%)は分離前にカルバペネム系薬の治療を行っていた。逐次臓器不全評価スコアは平均5.8で、高くなかった。MDRP株の約50%は、カルバペネム系薬以外のβラクタム系薬に耐性を示さなかった。メタロβラクタマーゼ産生株は分離されなかった。遺伝子解析により、16/20(80%)の分離株が同一のゲノムパターンを有することが示された。

Publishing type：Research paper (scientific journal)  

メチシリン耐性コアグラーゼ陰性ブドウ球菌血症患者70例(男性38例、女性32例、平均53.5歳)を対象に、臨床的特徴、グリコペプチド系薬剤の感受性を検討した。菌の同定を行った後、血球数とCRPの測定、好中球減少の評価、Sequential Organ Failure Assessment(SOFA)スコアを用いた重症度の判定を行い、抗菌薬を投与した。その結果、28例(40.0%)が白血病を有しており、36例(51.4%)が熱性好中球減少症に対する治療を受けていた。平均SOFAスコアは4.3であった。起因菌では表皮ブドウ球菌が78.6%を占めていた。39例(55.7%)が血管内カテーテルを留置され、ファーストライン治療としてテイコプラニンを投与されていたのは39例(55.7%)であり、バンコマイシンが12例(17.1%)、リネゾリドが3例(4.2%)に用いられていた。30日死亡率は4.3%であった。薬剤感受性に関しては、テイコプラニン非感受性菌が20%に達していた。また、多変量解析では、グリコペプチド系薬剤の前投与がテイコプラニン非感受性と独立して関連していた。メチシリン耐性コアグラーゼ陰性ブドウ球菌血症に対しては、抗菌薬耐性の発現を予防するためにグリコペプチド系薬剤を適切に投与する必要があると思われた。

メチシリン耐性コアグラーゼ陰性ブドウ球菌血症患者70例(男性38例、女性32例、平均53.5歳)を対象に、臨床的特徴、グリコペプチド系薬剤の感受性を検討した。菌の同定を行った後、血球数とCRPの測定、好中球減少の評価、Sequential Organ Failure Assessment(SOFA)スコアを用いた重症度の判定を行い、抗菌薬を投与した。その結果、28例(40.0%)が白血病を有しており、36例(51.4%)が熱性好中球減少症に対する治療を受けていた。平均SOFAスコアは4.3であった。起因菌では表皮ブドウ球菌が78.6%を占めていた。39例(55.7%)が血管内カテーテルを留置され、ファーストライン治療としてテイコプラニンを投与されていたのは39例(55.7%)であり、バンコマイシンが12例(17.1%)、リネゾリドが3例(4.2%)に用いられていた。30日死亡率は4.3%であった。薬剤感受性に関しては、テイコプラニン非感受性菌が20%に達していた。また、多変量解析では、グリコペプチド系薬剤の前投与がテイコプラニン非感受性と独立して関連していた。メチシリン耐性コアグラーゼ陰性ブドウ球菌血症に対しては、抗菌薬耐性の発現を予防するためにグリコペプチド系薬剤を適切に投与する必要があると思われた。

Publishing type：Research paper (scientific journal)  

Publishing type：Research paper (scientific journal)  

バンコマイシン(vancomycin:以下、VCM)は発熱性好中球減少症(febrile neutropenia:以下、FN)治療において、薬剤耐性グラム陽性菌感染時の標準的治療薬である。しかしながら、海外を含め小児FN患者を対象にVCMの有効性や安全性を検討した報告は少ない。そこで今回、がん化学療法実施後の小児FN患者において、VCM投与による有効性と安全性について検討した。期間は2008年1月〜2015年3月に16歳未満でVCMが投与されたFN症例を対象とした。対象症例は50例、平均年齢は8.1±4.1歳であった。VCMの投与量は39.6±3.7mg/kg/日、投与期間は9.6±5.4日であった。VCM投与による有効性評価が可能であった症例の有効率は61.5%(24/39例)、VCM投与終了30日後の生存率は96.0%(48/50例)であった。1例で薬疹によりVCM投与が中止となったが、腎機能障害による中止症例は確認されなかった。本検討結果からがん化学療法実施後の小児FN患者へのVCM投与の有効性と安全性が示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)  

バンコマイシン(vancomycin:以下、VCM)は発熱性好中球減少症(febrile neutropenia:以下、FN)治療において、薬剤耐性グラム陽性菌感染時の標準的治療薬である。しかしながら、海外を含め小児FN患者を対象にVCMの有効性や安全性を検討した報告は少ない。そこで今回、がん化学療法実施後の小児FN患者において、VCM投与による有効性と安全性について検討した。期間は2008年1月〜2015年3月に16歳未満でVCMが投与されたFN症例を対象とした。対象症例は50例、平均年齢は8.1±4.1歳であった。VCMの投与量は39.6±3.7mg/kg/日、投与期間は9.6±5.4日であった。VCM投与による有効性評価が可能であった症例の有効率は61.5%(24/39例)、VCM投与終了30日後の生存率は96.0%(48/50例)であった。1例で薬疹によりVCM投与が中止となったが、腎機能障害による中止症例は確認されなかった。本検討結果からがん化学療法実施後の小児FN患者へのVCM投与の有効性と安全性が示唆された。(著者抄録)

バンコマイシン(vancomycin:以下、VCM)は発熱性好中球減少症(febrile neutropenia:以下、FN)治療において、薬剤耐性グラム陽性菌感染時の標準的治療薬である。しかしながら、海外を含め小児FN患者を対象にVCMの有効性や安全性を検討した報告は少ない。そこで今回、がん化学療法実施後の小児FN患者において、VCM投与による有効性と安全性について検討した。期間は2008年1月〜2015年3月に16歳未満でVCMが投与されたFN症例を対象とした。対象症例は50例、平均年齢は8.1±4.1歳であった。VCMの投与量は39.6±3.7mg/kg/日、投与期間は9.6±5.4日であった。VCM投与による有効性評価が可能であった症例の有効率は61.5%(24/39例)、VCM投与終了30日後の生存率は96.0%(48/50例)であった。1例で薬疹によりVCM投与が中止となったが、腎機能障害による中止症例は確認されなかった。本検討結果からがん化学療法実施後の小児FN患者へのVCM投与の有効性と安全性が示唆された。(著者抄録)

CiNii Article

バンコマイシン(vancomycin:以下、VCM)は発熱性好中球減少症(febrile neutropenia:以下、FN)治療において、薬剤耐性グラム陽性菌感染時の標準的治療薬である。しかしながら、海外を含め小児FN患者を対象にVCMの有効性や安全性を検討した報告は少ない。そこで今回、がん化学療法実施後の小児FN患者において、VCM投与による有効性と安全性について検討した。期間は2008年1月～2015年3月に16歳未満でVCMが投与されたFN症例を対象とした。対象症例は50例、平均年齢は8.1±4.1歳であった。VCMの投与量は39.6±3.7mg/kg/日、投与期間は9.6±5.4日であった。VCM投与による有効性評価が可能であった症例の有効率は61.5%(24/39例)、VCM投与終了30日後の生存率は96.0%(48/50例)であった。1例で薬疹によりVCM投与が中止となったが、腎機能障害による中止症例は確認されなかった。本検討結果からがん化学療法実施後の小児FN患者へのVCM投与の有効性と安全性が示唆された。(著者抄録)

Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

DOI： 10.11534/jsmm.58.Suppl1.0_46_2

CiNii Article

Publishing type：Research paper (scientific journal)  

<p><b>Objective </b>Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides. </p><p><b>Methods </b>We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013. We evaluated the patients' background, severity and prognosis of the disease, and the susceptibility of the isolated methicillin-resistant coagulase-negative staphylococci to glycopeptides. </p><p><b>Results </b>Out of the 70 patients tested, 28 (40.0%) had leukemia, and 36 (51.4%) had been treated for febrile neutropenia. Infection with <i>Staphylococcus epidermidis</i> accounted for 78.6% of patients. Thirty-nine cases (55.7%) were related to intravascular catheters, and 39 (55.7%) were treated using teicoplanin as a first-line therapy. The 30-day mortality rate was 4.3%. Regarding susceptibility, 20% of all isolates were non-susceptible to teicoplanin. According to multivariate analyses, it was observed that premedication using glycopeptides was independently associated with teicoplanin non-susceptibility (p=0.03; hazard ratio = 5.64; 95% confidence interval, 1.16-26.76). </p><p><b>Conclusion </b>Our results suggest that clinicians must use glycopeptides appropriately to prevent the development of further antibiotic resistance in methicillin-resistant coagulase-negative staphylococci. </p>

DOI： 10.2169/internalmedicine.56.7715

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

DOI： 10.1093/ofid/ofx129

PubMed

Publishing type：Research paper (scientific journal)  

<p><b>Objective </b>In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL <i>Enterobacteriaceae</i> and non-ESBL <i>Enterobacteriaceae</i> are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL <i>Escherichia coli</i> (<i>E. coli</i>). </p><p><b>Methods </b>The medical records of 31 patients with ESBL <i>E. coli</i> bacteremia and 98 patients with non-ESBL <i>E. coli</i> bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated. </p><p><b>Results </b>The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL <i>E. coli</i> bacteremia and non-ESBL <i>E. coli</i> bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL <i>E. coli</i> bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL <i>E. coli</i> bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p=0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL <i>E. coli</i> bacteremia. </p><p><b>Conclusion </b>Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL <i>E. coli</i> in mind. </p>

DOI： 10.2169/internalmedicine.56.7702

PubMed

CiNii Article

<p><b>Objective </b>In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL <i>Enterobacteriaceae</i> and non-ESBL <i>Enterobacteriaceae</i> are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL <i>Escherichia coli</i> (<i>E. coli</i>). </p><p><b>Methods </b>The medical records of 31 patients with ESBL <i>E. coli</i> bacteremia and 98 patients with non-ESBL <i>E. coli</i> bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated. </p><p><b>Results </b>The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL <i>E. coli</i> bacteremia and non-ESBL <i>E. coli</i> bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL <i>E. coli</i> bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL <i>E. coli</i> bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p=0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL <i>E. coli</i> bacteremia. </p><p><b>Conclusion </b>Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL <i>E. coli</i> in mind. </p>

DOI： 10.2169/internalmedicine.56.7702

PubMed

CiNii Article

DOI： 10.11534/jsmm.58.suppl1.0_46_2

CiNii Article

Publishing type：Research paper (scientific journal)   International / domestic magazine：International journal  

BACKGROUND: Clinical studies comparing the different neuraminidase inhibitors for treatment of at-risk patients with influenza have not been performed. To optimize such treatments, we assessed the efficacy and safety of intravenous peramivir compared with oral oseltamivir in treating seasonal influenza A or B virus infection. METHODS: A multicenter, randomized, controlled clinical trial was conducted from December 2012 to May 2014 in high-risk patients infected with seasonal influenza. A total of 92 adult inpatients and outpatients with high risk factors (HRFs) were treated by either a single intravenous infusion of peramivir (600 mg) or oral administration of oseltamivir (75 mg, twice per day for 5 days). RESULTS: The median times to clinical stability (time to reach <37°C) were 40.0 hours (95% confidence interval [CI] = 23.3-64.5) and 37.8 hours (95% CI = 26.3-45.3) in the peramivir and oseltamivir groups, respectively; these values did not reveal a significant difference. The virus titer and change of mean total symptom scores decreased similarly with both treatments. Results of step-wise regression suggested that virus type was a significantly effective prognostic factor with respect to illness resolution. Adverse events (AEs) with peramivir and oseltamivir occurred in 2.2% (n = 1/46) and 13.0% (n = 6/46) of patients, respectively. The severity of AEs was mild in all cases except 2 patients who showed pneumonia or COPD aggravation; both were in the oseltamivir group. CONCLUSIONS: Intravenous peramivir was effective based on the result of direct comparison with oral oseltamivir. Thus our data show that peramivir is a useful option for the treatment of influenza-infected patients with HRFs.

DOI： 10.1093/ofid/ofx129

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

<p><b>Objective </b>Coagulase-negative staphylococci are among the most frequently isolated microorganisms in blood cultures. The aim of this study was to assess [1] the clinical characteristics of methicillin-resistant, coagulase-negative staphylococci bacteremia and [2] the susceptibility of the isolated bacteria to glycopeptides. </p><p><b>Methods </b>We retrospectively reviewed the medical records of 70 patients from whom methicillin-resistant coagulase-negative staphylococci had been isolated at Osaka City University Hospital between January 2010 and December 2013. We evaluated the patients' background, severity and prognosis of the disease, and the susceptibility of the isolated methicillin-resistant coagulase-negative staphylococci to glycopeptides. </p><p><b>Results </b>Out of the 70 patients tested, 28 (40.0%) had leukemia, and 36 (51.4%) had been treated for febrile neutropenia. Infection with <i>Staphylococcus epidermidis</i> accounted for 78.6% of patients. Thirty-nine cases (55.7%) were related to intravascular catheters, and 39 (55.7%) were treated using teicoplanin as a first-line therapy. The 30-day mortality rate was 4.3%. Regarding susceptibility, 20% of all isolates were non-susceptible to teicoplanin. According to multivariate analyses, it was observed that premedication using glycopeptides was independently associated with teicoplanin non-susceptibility (p=0.03; hazard ratio = 5.64; 95% confidence interval, 1.16-26.76). </p><p><b>Conclusion </b>Our results suggest that clinicians must use glycopeptides appropriately to prevent the development of further antibiotic resistance in methicillin-resistant coagulase-negative staphylococci. </p>

DOI： 10.2169/internalmedicine.56.7715

PubMed

CiNii Article

Publishing type：Research paper (scientific journal)  

Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli).
Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated.
Results The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL E. coli bacteremia and non-ESBL E. coli bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL E. coli bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL E. coli bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p= 0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL E. coli bacteremia.
Conclusion Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL E. coli in mind.

DOI： 10.2169/internalmedicine.56.7702

PubMed

Publishing type：Research paper (scientific journal)   International / domestic magazine：Domestic journal  

Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli).
Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed. The patient backgrounds, risk factors for infection, and prognosis were evaluated.
Results The male-to-female ratio, mean age, underlying disease, leukocyte count, and C-reactive protein (CRP) level did not differ between the patients in the ESBL E. coli bacteremia and non-ESBL E. coli bacteremia groups. The mean Sequential Organ Failure Assessment (SOFA) score for patients with ESBL and non-ESBL E. coli bacteremia were 3.6 and 3.8, respectively. Further, the mortality did not differ between the two groups (9.7% vs 9.2%). However, the independent predictors associated with ESBL E. coli bacteremia according to a multivariate analysis were the use of immunosuppressive drugs or corticosteroids (p=0.048) and quinolones (p= 0.005) prior to isolation. The mortality did not differ between the carbapenem and tazobactam/piperacillin (TAZ/PIPC) or cefmetazole (CMZ) groups for the patients with ESBL E. coli bacteremia.
Conclusion Whenever we encountered patients with a history of immunosuppressive drug, corticosteroid, quinolone administration, it was necessary to perform antibiotic therapy while keeping the risk of ESBL E. coli in mind.

DOI： 10.2169/internalmedicine.56.7702

PubMed

Publishing type：Research paper (scientific journal)  

新たなメチシリン耐性黄色ブドウ球菌(MRSA)株の分析におけるpolymerase chain reaction-based open reading frame typing(POT)の利用と週1回の全株検査の有用性について検討した。当院では新たに検出された全てのMRSA株について、2014年は月に1回POTを行っていたが、2015年には実施回数を週に1回に増やした。その結果、通常は検出することが難しい院内感染を検出できるようになり、院内感染が2014年に比べて40%減少した。MRSA全株に対する毎週のPOTスクリーニングはMRSA院内感染を最小限に抑えるために利用できる効果的な方法の一つであると考えられた。