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Introduction Evidenced based medicine (EBM) is necessary to standardize or treatment for infection since EBM is established based on the results of clinical trials. Entry criteria for clinical trials are very strict, and many patients have difficulties in being enrolled in any clinical trials regarding candidemia. It is questionable if the results of clinical trials reflect the real world of general medicine in this case. Patients and methods For the purpose of examining how many patients could join any randomized clinical trials for the treatment of candidemia, we reviewed all the candidemia patients in our institute during 2014–2018. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials. Results A total of 70 patients was enrolled in this study. The median age was 73 years (range 36–93 years). Of these, 41 patients (59%) were male. As for site of infections, catheter related blood stream infection was most frequently seen in 37 (53%). Seventeen patients (24%) were classified as participation possible group and 53 patients (76%) were participation impossible group. Comparing the two groups, participation possible group patients have much better performance status, have less comorbidities and have longer overall survival times than participation impossible group patients. Conclusion Only 24% of candidemia patients were eligible for the clinical trials. Thus, we can see that clinical trials might not correctly reflect the real world among candidemia patients.

Introduction The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 diagnostic test (SmartAmp) was licensed in Japan in July 2021. This method, which enables us to diagnose COVID-19 as well as a gene mutation on the virus, is promising to reduce medical costs and staff labor. Patients and methods To analyze the diagnostic accuracy of the SmartAmp assay for diagnosing COVID-19, we performed this retrospective study at our institute during April and May 2021. We compared the results of the SmartAmp assay and real-time reverse transcription-polymerase chain reaction (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. Results Out of 70 samples tested, the SmartAmp assay had 50 (71%) positive and 20 (29%) negative results. Using rRT-PCR as a reference, the diagnostic accuracy displayed a sensitivity of 84%, a specificity of 95%, a positive predictive value of 97.7%, and a negative predictive value of 70.4%. On the other hand, false-negative cases were found in 7 (10%), and there was no significant difference of Ct-value between true positive and false negative cases (Mean Ct-value 25.2 vs. 27.5 cycles, p = 0.226 by Mann-Whitney U test). Conclusion The SmartAmp assay is a valuable method to diagnose COVID-19 rapidly. However, the negative predictive value is not high enough to diagnose the disease, so that negative results should be considered for rRT-PCR testing if patients are suspected of having COVID-19.

Objectives: Procalcitonin (PCT) is an early diagnosis marker of sepsis/bacteremia. However, some reports refer to its lower responsiveness to gram-positive bacteremia. We retrospectively evaluated the PCT values at the onset of bacteremia in relation to severity index. Methods: Patients with bacteremia caused by two gram-negative bacteria (46 E. coli and 50 Klebsiella pneumoniae) and three gram-positive bacteria (45 S. aureus, 56 S. epidermidis, and 10 S. mitis) were studied. The plasma PCT and C-reactive protein (CRP) levels were compared between species and different Sequential Organ Failure Assessment (SOFA) score groups. Results: The median PCT level was higher in gram-negative than in gram-positive bacteremia in overall (13.09 vs. 0.50 ng/mL, p

Background Current guidelines recommend echinocandins for the initial treatment of candidemia. However, polyenes are often chosen in clinical settings because of their fungicidal and anti-biofilm effects. Therefore, we performed a systematic review and meta-analysis to evaluate whether echinocandins are superior to polyenes in terms of mortality for the initial treatment of candidemia. Methods We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL databases until July 1, 2020. We compared the mortality rates of patients who received echinocandins and polyenes. As a subgroup analysis, we compared the mortality rates following the use of echinocandins versus liposomal amphotericin B. Results Fifteen studies involving 854 patients were included. Various Candida species were detected, and the rates of resistance of echinocandins and polyenes against the overall detected isolates were 1.0% and 0%, respectively. The overall mortality recorded in 15 studies was 41.0%, and the mortality was significantly higher for polyenes than echinocandins (odd ratios [OR] 1.68, 95% confidential interval [CI] 1.17–2.42). Furthermore, liposomal amphotericin B showed higher mortality in the initial treatment than echinocandins (OR 1.42; 95% CI 0.84–2.39). Conclusions We revealed an association between echinocandin treatment and reduced mortality in the initial treatment of candidemia when causative fungi were not considered. Our findings partially support current guidelines recommending echinocandins for the treatment of candidemia.

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

Introduction The novel coronavirus disease (COVID-19) could cause a severe acute respiratory infectious disease, showing a high mortality rate of 12-45% among cases who required intensive care unit admission. COVID-19 pneumonia Patients and methods For the purpose of identifying clinical manifestations and radiological findings of COVID-19 pneumonia, we reviewed all cases of COVID-19 pneumonia which were published by the homepage of the Japanese Association for Infectious Diseases from Feb 5 2020 until April 30 2020, including our cases. All patients were diagnosed based on positive results of the novel coronavirus-real-time RT-PCR with chest computed tomography (CT) findings. Results A total of 92 patients were enrolled in this study. The median age was 66 years (range 16-92 years). For all, 50 (54%) were males. The most common underlying disease was hypertension in 32 (36%). Any comorbidity was seen in 60 (67%). The mortality rate was 4 (6%). In terms of clinical symptoms on an initial visit, fever and cough were confirmed in 66 (72%) and 37 (40%). Forty-three (47%) had no respiratory symptoms. As for radiological findings by chest CT scan, ground-glass opacities (GGO)s, peripheral distribution, bilateral lung involvements were seen in 88 (96%), 76 (83%) and 78 (85%), respectively. Conclusion It is difficult to diagnose as COVID-19 pneumonia due to poor respiratory symptoms. Chest CT findings typically show GGO, peripheral and bilateral shadows. Patients should have chest CT performed if suspected for early diagnosis and therapeutic intervention, resulting in a favorable outcome and prevention of secondary nosocomial transmitted infection.

Introduction While necrotizing fasciitis (NF) is a rare but rapidly progressive devastating soft tissue infectious disease showing a high in-hospital mortality rate of 20–30%, there are no evidence-based predictive tools. Patients and methods For the purpose of examining which predictive tools could correctly reflect the severity and prognosis of NF, we retrospectively reviewed all patients who were diagnosed with NF at our institute. The disease severity was evaluated by quick SOFA (qSOFA), SOFA score, SIRS score, APACHE II score, LRINEC score and the combined score of qSOFA and CCI. Results A total of 27 patients were enrolled in this study. The median age was 68 years (range 39–96 years). With respect to the predictive values for in-hospital mortality among NF patients, the area under the ROC curve for qSOFA, SOFA score, APACHE II score, the combined score of qSOFA and CCI were 0.653 (p = 0.192), 0.588 (p = 0.12), 0.709 (p = 0.075) and 0.782 (p = 0.016) respectively. A univariate analysis showed that the combined score of qSOFA and CCI≥5 and the initial treatment failure were poor prognostic indicators for the in-hospital death among NF patients. The appropriate cut-offs of qSOFA and CCI were based on the Youden Index. Conclusion We concluded that the combined score of qSOFA and CCI could reflect the severity and prognosis of NF for in-hospital death.

We report a case of prosthetic arthritis caused by Cardiobacterium valvarum, which has been exclusively reported to cause intravascular infections. A 81-year-old Japanese female complained prosthetic knee joint pain. Arthrocentesis cultured no pathogen, and surgical replacement of the implant surface was performed. Modified Levinthal medium culture and 16S rRNA sequencing has finally led to diagnosis of C. valvarum prosthetic knee arthritis without cardiac lesions. Fastidious bacteria such as C. valvarum can be candidate pathogens of orthopedic infections whose causative agents are sometimes unidentified. Further development of molecular diagnostics is expected, but also the importance of conventional methods should be noted.

Objective American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a systematic review and comparative meta-analysis to compare VCM and LZD efficacy against proven MRSA pneumonia. Methods We searched EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed up to November 2019. The outcomes of the meta-analysis were mortality, clinical cure, microbiological evaluation, and adverse events. Results Seven randomized controlled trials (RCTs) with a total of 1239 patients and eight retrospective cohort or case–control studies (CSs) with a total 6125 patients were identified. Clinical cure and microbiological eradication rates were significantly increased in patients treated with LZD in RCTs (clinical cure: risk ratio (RR) = 0.81, 95% confidential interval (CI) = 0.71–0.92; microbiological eradication: RR = 0.71, 95% CI = 0.62–0.81) and CSs (clinical cure: odds ratio (OR) = 0.35, 95% CI = 0.18–0.69). However, mortality was comparable between patients treated with VCM and LZD in RCTs (RR = 1.08, 95% CI = 0.88–1.32) and CSs (OR = 1.20, 95% CI = 0.94–1.53). Likewise, there was no significant difference in adverse events between VCM and LZD in CSs (thrombocytopenia: OR = 0.95, 95% CI = 0.50–1.82; nephrotoxicity: OR = 1.72, 95% CI = 0.85–3.45). Conclusions According to our meta-analysis of RCTs and CSs conducted worldwide, we found robust evidence to corroborate the IDSA guidelines for the treatment of proven MRSA pneumonia.

Objectives This study evaluated the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae isolates from adults (aged ≥20 years) with invasive pneumococcal disease (IPD) in Japan. Methods This prospective observational study was conducted in 49 participating Japanese hospitals. S. pneumoniae isolates were serotyped and tested for antimicrobial susceptibility at a central laboratory. Information regarding patient characteristics, underlying disease, IPD clinical syndromes, and treatment was collected through medical chart review. Results The final analysis included 177 patients enrolled from 45 hospitals between September 2016 and April 2018 (bacteraemic pneumonia, 110; bacteraemia without identified focus, 29; meningitis, 19). Most patients (70.1%) were aged ≥65 years and most had underlying disease (79.1%). The proportion of isolates from serotypes contained in the pneumococcal polysaccharide vaccine (PPV) 23 was 61.0%, while those in the pneumococcal conjugate vaccine (PCV) 7 and PCV13 were 2.8% and 28.2%, respectively. Non-vaccine serotypes accounted for 37.9% of all isolates and 50.8% of isolates from immunosuppressed patients. Serotype 12F was the most common vaccine serotype, followed by serotype 3. Conclusions The continued disease burden of IPD in adults in Japan warrants improved vaccination rates and development of next-generation vaccines that include serotypes not currently covered. Clinical trial registration Clinical trial summary registration number 160,822,918,146; JapicCTI-163352.

In patients infected with human immunodeficiency virus (HIV)-1 at our hospital, we observed increases in skin and soft-tissue infections (SSTIs) by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Therefore, we analyzed factors related to CA-MRSA infection and performed a molecular epidemiological investigation.HIV-1-infected patients were diagnosed with SSTIs related to S. aureus between 2007 and 2017, and MRSA was classified into community and hospital-acquired types according to published criteria. Information was collected retrospectively from clinical records, and multivariate analysis by logistic regression was performed concerning factors related to CA-MRSA infection. We evaluated the staphylococcal cassette chromosome mec (SCCmec) type, multilocus sequence type, and the presence of genes encoding Panton-Valentine leucocidin (PVL) in 27 MRSA samples isolated during and after 2015.We found 218 episodes of SSTIs in 169 patients, and among initial episodes of SSTIs, the MRSA ratio was higher from 2015 to 2017 relative to that from 2007 to 2014 (88% vs. 44%; p 0.0001). Multivariate analysis showed that in men having sex with men [MSM; odds ratio (OR): 13] and exhibiting onset during and after 2015 (OR: 5.4), CD4These data describe an increased prevalence of SSTIs due to PVL-positive ST8-MRSA-IV, not previously considered epidemic in Japan, in MSM infected with HIV-1 in Osaka, Japan.

Linezolid has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants. Major adverse events associated with linezolid treatment is cytopenia. However, there were few reports about the relationship between cytopenia and gestational age. Primary objective of this study was to compare the relationship between cytopenia in infants and neonates treated with linezolid therapy and gestational age.In total, 44 patients were divided into two groups depend on their gestational age [180 days; low gestational age group (20 patients);180 days group; high gestational age group (24 patients)]. All patients treated with linezolid from April 2014 to March 2018 at NICU or GCU of Aichi Medical University Hospital. Investigation items were as follows; sex, age, weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, concomitant medications, hematologic abnormalities during linezolid treatment.The incidence of overall cytopenia in low gestational age group was significantly higher than high gestational age group (65.0 % vs. 25.0 %; p0.05). Of note, the incidence of thrombocytopenia in low gestational age group showed significantly higher than high gestational age group (45.0% vs. 8.3%, p 0.05). Then, the proportion of patients occurred thrombocytopenia who received linezolid 10 mg/kg every 8 h were higher than 10 mg/kg every 12 h in both groups.In cases linezolid is administered three times a day should be more carefully of thrombocytopenia in patients with gestational days less than 180 days.

Introduction Although infectious endocarditis (IE) is a potentially severe infectious disease, there are no prognostic tools for in-hospital mortality for IE patients. This is the first report documenting that the Sequential Organ Failure Assessment (SOFA) score could evaluate the severity and outcome among IE patients. Patients and methods From 2007 to 2018, we reviewed all patients who were diagnosed as having IE at our institue. Patients diagnosed as definite IE according to the modified Duke criteria or by surgical procedure were included in this study. Results A total of 66 IE patients were enrolled in this study. They were 45 males (68%) and the median age was 70 years. As for prognostic factors for in-hospital death among IE patients, SOFA score ≥6, CCI ≥3, surgical procedure, heart failure, immunological phenomena and detection of S. aureus as a causative pathogen were identified as prognostic factors by univariate analysis. Of these 6 factors, SOFA score ≥6 (OR 7.6, 95%CI 1.3–46.6, p = 0.029), heart failure (OR 9.7, 95%CI 1.1–86.1, p = 0.042), surgery (OR 0.1, 95%CI 0–0.8, p = 0.037) and immunological phenomena (OR 0.1, 95%CI 0–0.9, p = 0.042) were independent prognostic factors for in-hospital mortality among IE by logistic regression analysis. Conclusion The SOFA score could be a good prognostic tool to use for IE patients. Also, SOFA score ≥6, surgery, immunological phenomena and heart failure were independent prognostic factors for in-hospital mortality among IE patients.

Since 2018, high expectations have been placed on the efforts of pharmacists in infectious disease diagnostic aid via Japan's antimicrobial stewardship team (AST). We will explain this while describing the process of diagnostic aid at our institution, a university hospital, and taking into account the point of view of what is required of pharmacist by infection control doctors when performing infectious disease diagnostic aid as well. At our hospital, we implement AST rounds as infectious disease diagnostic aid for positive blood cultures, bacterial culture results, fever, long-term administration of anti-bacterial medication, example consultation cases, etc. The number of rounds has been increasing over time, totaling 5654 cases in 2018. When performing infectious disease diagnostic aid, failure to also bear in mind infection control measures can result in failed treatment and outbreaks, so AST must coordinate with infection control team (ICT). Furthermore, when engaging in infectious disease diagnostic aid, pharmacists must also participate in clinical research in order to improve the quality of treatment. Although it also depends on the facility environment they are affiliated with, it would seem to be necessary for pharmacists to verify the knowledge obtained from clinical data using a fundamental approach. Moreover, conducting education for the doctor, pharmacist, and nurse trainees who make up their fellow and future staff is another vital role of AST pharmacists.

BackgroundEvidenced based medicine (EBM) is necessary to standardize treatments for infections because EBM has been established based on the results of clinical trials. Since entry criteria for clinical trials are very strict, it ​may cause skepticism or question whether the results of clinical trials reflect the real world ​of medical practice.MethodsTo examine how many patients could join any randomized clinical trials for the treatment of community-onset pneumonia, we reviewed all the pneumonia patients in our institute during 2014-2017. The patients were divided into two groups: patients who were eligible for clinical trials (participation possible group), and those who were not (participation impossible group). Exclusion criteria for clinical trials were set based on previous clinical trials.ResultsA total of 406 patients were enrolled in the present study. Fifty-seven (14%) patients were categorized into the participation possible group, while 86% ​of patients belonged to the participation impossible group. Patients in the participation possible group had less comorbidities and ​more favorable outcomes than those with the participation impossible group. As for the outcomes, there were significant differences in the 30-day and in-hospital mortality rates between the two groups. In addition, the participation possible group showed a longer overall survival time than the participation impossible group (p Log-Rank test).ConclusionThere is a difference in patients’ profile and outcomes between clinical trials and the real world. Though EBM is essential to advance ​medicine, we should acknowledge the fact​s and the limit​s of the clinical trial.

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.

We herein report the findings of the Japan Postoperative Infectious Complication Survey in 2015 (JPICS'15), which evaluated the rate of post-operative infections and colonization due to antimicrobial-resistant (AMR) bacteria after digestive tract surgery. This survey by the Japan Society of Surgical Infection included patients undergoing digestive tract surgery at 28 centers between September 2015 and March 2016. Data included patient background characteristics, type of surgery, contamination status, and type of post-operative infections, including surgical site infections (SSIs), remote infections (RIs), and colonization. During the study period, 7,565 surgeries (of 896 types) were performed; among them, 905 cases demonstrated bacteria after digestive tract surgery. The survey revealed that post-operative infections or colonization by AMR bacteria occurred in 0.9% of the patient cohort, constituting 7.5% of post-operative infections, including 5.6% of SSIs and 1.8% of RIs. Extended-spectrum β-lactamase-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus were the predominant AMR bacteria isolated from patients after digestive tract surgery. Patients infected with AMR bacteria had a poor prognosis. Our results reveal that 7.5% of the post-operative infections were due to AMR bacteria, indicating the need for antibacterial coverage against AMR bacteria in patients with critical post-operative infections.

Background While it has been increasing cases of C. hominis endocarditis in the past decades due to advances of diagnostic methods, the epidemiology and clinical manifestations of IE caused by C. hominis is still unknown. Case presentation A 62-year old man was admitted to our institute with fever, anorexia and general fatigue for the preceding one month. He had a past medical history of both aortic and mitral valves replacement due to cardiac diseases. He was diagnosed as IE caused by C. hominis according to the modified duke criteria. The patient received 2 weeks of combination therapy of intravenous ceftriaxone (CTRX) 2g and gentamycin 180mg daily followed by 4 weeks CTRX 2g daily alone. Oral moxifloxacin 400mg once daily was given for an additional 4 weeks. After the antibiotic therapy was discontinued, disease recurrence was not observed. We reviewed previously reported C. hominis IE cases in 60 publications including ours. Of 73 patients enrolled, 53 were male, the mean age was 52 years. The most common risk factor of IE was past history of cardiac diseases in 44/73 (60%). As for antibiotics initially prescribed, third-generation cephalosporins was most frequently used in 28/69 (41%). While the cure rate was 67/73 (93%), 31/73 patients (43%) received a surgical intervention. Embolic lesions to the central nervous system and vertebrae were seen in 16/72 (22%) and 5/72 (7%). Conclusion IE caused by C. hominis has a favorable prognosis, showing the cure rate of 93%. Physicians should recognize the possible occurrence of emboli among IE patients.

To report the clinical manifestations, identification, antimicrobial susceptibilities, and treatment outcomes of ocular infections caused by Moraxella species. Retrospective study. The medical records of all patients treated at the Departments of Ophthalmology of the Ogaki Municipal Hospital and the Gifu University Graduate School of Medicine for ocular infections caused by Moraxella species between January 2011 and June 2017 were examined. The stored Moraxella species isolated from ocular samples were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), molecular identification, and the biochemical properties. Sixteen eyes of 16 patients were treated for Moraxella ocular infections. The patients’ median age was 72 years. A predisposing systemic or ocular condition was identified in 15 of the patients. Nine of the patients developed keratitis; four, conjunctivitis; and three, blebitis. M lacunata (6 eyes), M catarrhalis (6), M nonliquefaciens (3), and M osloensis (1) were identified by MALDI-TOF MS. All isolates were sensitive to levofloxacin, tobramycin, ceftazidime, ceftriaxone, and cefazolin. Twelve patients with keratitis or blebitis were treated with various topical antimicrobial combinations, and systemic antibiotics were used in 10 of the 12 patients. The mean time for the complete closure of the epithelial defects with keratitis was 24 days. The visual outcomes after treatment were favorable except in 1 keratitis patient who underwent enucleation. The use of duo-therapy with a combination of fluoroquinolone and cefmenoxime should be considered in cases nonresponsive to monotherapy, such as keratitis and bleb-associated infections. MALDI-TOF MS is useful for the identification of Moraxella to the species level.

The quadrivalent (q) human papillomavirus (HPV) vaccine protects against infection and disease related to HPV types 6, 11, 16, and 18. We report efficacy, immunogenicity, and safety of qHPV vaccine in a Phase 3 study in Japanese men.In this randomized, double-blind trial (NCT01862874), Japanese men (aged 16-26 years) were randomized in a 1:1 ratio to receive three doses of qHPV vaccine or placebo (Day 1, Month 2, Month 6). The primary efficacy endpoint was the combined incidence of HPV6/11/16/18-related persistent anogenital infection (detected at ≥2 consecutive visits ≥6 months apart), assessed in the per-protocol population of men who received all three vaccinations, and were seronegative at Day 1 and PCR negative from Day 1 to Month 7 to the relevant HPV type. Results are from the interim and final analyses.In total, 1124 participants were randomized. The vaccine demonstrated 83.3% (95% confidence interval: 24.9, 98.2; p = 0.007) and 85.9% (95% confidence interval: 52.7, 97.3; p 0.001) efficacy against HPV6/11/16/18-related persistent infection in the interim and final analyses, respectively. Two cases of HPV6/11/16/18-related external genital lesions (condyloma and PIN 1) were observed in the placebo group and none in the qHPV vaccine group at study end. At Month 7,97% of participants who received qHPV vaccine seroconverted to each of the vaccine HPV types. Most participants remained seropositive at Month 36, although the seropositivity rate declined between Months 7 and 36. Vaccination-related adverse events were reported in 60.8% and 56.5% of participants in the qHPV vaccine and placebo groups, respectively; most commonly mild to moderate injection-site pain, erythema, and swelling. Injection-site pain and swelling were more common with qHPV vaccine than placebo (each p 0.05).Results suggest qHPV vaccine is efficacious against HPV6/11/16/18-related persistent infections, immunogenic, and well-tolerated in Japanese men. Clinical trial registration identifier: NCT01862874.

Tazobactam/ceftolozane, a novel antimicrobial therapy, is active against Pseudomonas aeruginosa and most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. We report the results of the efficacy and safety of tazobactam/ceftolozane in Japanese patients with complicated intra-abdominal infections (cIAI). A multicenter, open-label, noncomparative study (MK-7625A Protocol 013, ClinicalTrials.gov Identifier: NCT02739997 ) to investigate the efficacy and safety of tazobactam/ceftolozane used in combination with metronidazole in Japanese patients with cIAI was conducted. One hundred Japanese patients with cIAI received tazobactam/ceftolozane 1.5 g (tazobactam 0.5 g/ceftolozane 1 g) plus metronidazole 500 mg intravenously every 8 h for 60 min for 4–14 days. The clinical response rate at the Test-of-Cure visit (TOC; Day 28 ± 2 days) was 92.0% (81/88 subjects). By disease type, the clinical response rates were 92.3% (24/26) for cholecystitis, 100% (6/6) for liver abscess, 93.5% (58/62) for intra-abdominal abscess and 90.2% (55/61) for peritonitis. The per-subject microbiological response rate at the TOC was 90.2% (55/61). Per-pathogen microbiological response rates in the most common baseline pathogens were Escherichia coli 90.2% (37/41), Kebsiella pneumoniae 91.7% (11/12), Streptococcus anginosus 100% (11/11), Streptococcus constellatus 90.0% (9/10) and Bacteroides fragilis 95.2% (20/21). The most common drug-related AEs were aspartate aminotransferase increased (11.0%) and alanine aminotransferase increased (9.0%). No serious drug-related AE was reported during the study. The favorable effect of tazobactam/ceftolozane in the treatment of cIAI suggests that the agent will be useful in clinical practice in Japan.

INTRODUCTION: The pandemic of a novel coronavirus disease 2019 (COVID-19) caused by a severe acute respiratory coronavirus 2 (SARS-CoV-2) infection has been problematic worldwide. A new SARS-CoV-2 antigen test (LUMIPULSEⓇ) was licensed and widely used in Japan since May 2020. We conducted this study intending to whether the automated quantitative CLEIA antigen test using a saliva sample is effective and valid for the diagnosis of COVID-19. PATIENTS AND METHODS: We analyzed and compared the diagnostic accuracy of both the automated quantitative CLEIA antigen test and real-time RT-PCR (rRT-PCR) using a saliva sample from individuals suspected as having COVID-19. RESULTS: A total of 305 samples were collected and tested in Aichi Medical University Hospital and affiliated facilities from December 2020 until January 2021 at our institute. Using reverse-transcription PCR as a reference, the AUROC of the automated quantitative CLEIA antigen test was 0.903 (95% confidential interval 0.845-0.962, p

Introduction Aspiration pneumonia (AP) accounts for 5.0–53.2% of hospitalized pneumonia and the treatment commonly used is by broad-spectrum antibiotics to cover anaerobes. Since ceftriaxone (CTRX) could generally cover oral streptococcus and anaerobes implicated in AP, it could be a useful option in the treatment of AP, instead of piperacillin-tazobactam/(PIPC/TAZ) or Carbapenems. Patients and methods For the purpose of examining whether CTRX is as effective as broad-spectrum antibiotics for the treatment of AP, this retrospective study included consecutive community-onset patients who were admitted to our institute between 2014 and 2017. These patients were divided into two groups, a CTRX group (n = 25) and a PIPC/TAZ or carbapenems group (n = 97) based on the initial antibiotic treatment. Propensity score matching (PSM) was used to balance the potential confounders, and 23 patients were selected from each group. Patients among CTXR group received CTRX, while those among PIPC/TAZ or carbapenems group received PIPC/TAZ, or carbapenems and/or other agents. Results Both groups were well-balanced after PSM. There were no differences in 30-day mortality, duration of hospital stay or antibiotic treatments in the between them. The medical costs were much more expensive in the PIPC/TAZ or carbapenems group than in the CTR group (35,582 v. s. 8678 Japanese yen, p Conclusion CTRX is one of the most useful antibiotic treatment for AP, which is not inferior to broad-spectrum antibiotic treatment. In addition, usage of CTRX in the treatment of AP is more economical than broad-spectrum antibiotic treatment, and could contribute to reduction of medical costs.

Background The incidence of linezolid-induced myelosuppression in pediatric patients was reported at large difference among prospective studies, with a range of 0–24%. Additionally, there is little study which evaluated the impact of linezolid administration period on myelosuppression in pediatric patients, while it is one of the most frequent reason that linezolid therapy has to be discontinued in adult patients. Here, we performed a systematic review and meta-analysis to reveal the incidence of linezolid-induced thrombocytopenia and anemia, and impact of the administration period of linezolid on myelosuppression based on individual data analysis of pediatric patients. Methods We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed, and CINAHL until April 2020. We investigated the incidence of linezolid-induced thrombocytopenia and anemia using pooled analysis, and evaluated the impact of linezolid administration period on myelosuppression using meta-analysis. Results Thirteen studies with 969 pediatric patients were identified. The pooled incidences of thrombocytopenia and anemia were 9% (95% confidence interval (CI), 3–18%) and 4% (95% CI, 0–12%), respectively. Our meta-analysis showed the extension of linezolid administration period (more than 14 days) resulted in higher incidence of thrombocytopenia (OR 4.86, 95% CI 1.10–21.55) and anemia (OR 4.57, 95% CI 0.13–160.49). Conclusions The incidence of linezolid-induced myelosuppression in pediatric patients was less than 10%. However, our meta-analysis revealed linezolid administration period for more than 14 days was one of risk factors associated with linezolid-induced myelosuppression. Therefore, especially for pediatric patients treated with linezolid for more than 14 days, careful monitoring of myelosuppression is required.

While the early diagnosis of necrotizing fasciitis (NF) is crucial and could lead to a favorable outcome, it is difficult to differentiate NF from cellulitis, resulting in delay for the appropriate treatment.For the purpose of examining which diagnostic tools could correctly differentiate NF from cellulitis, we conducted this case-control study. We retrospectively reviewed all patients who were diagnosed with NF at our institute during 2014-2019. The patients who were diagnosed with cellulitis were randomly selected during the study period as the control group. The severity of NF is evaluated by serum-procalcitonin (PCT), LRINEC score, NTSI assessment and SIARI score.A total of 25 NF patients were enrolled in this study. The median age was 68 years (range 39-79) and 18 (72%) were male. Comparing NF and cellulitis groups, NF group showed a higher LRINEC score and serum PCT than cellulitis group did, even though there was no statistical significance in serum PCT. With respect to the diagnostic value for differentiating NF from cellulitis, the area under the ROC curve for of serum PCT and LRINEC scores were 0.928 [95% confidential interval (CI) 0.864-0.992, p 0.001] and 0.846 (95% CI 0.757-0.936, p 0.001). The appropriate serum-PCT cutoff value was 1.0 and had a sensitivity of 88%, a specificity of 89%, a positive predictive value of 81%, and a negative predictive value of 93%.Serum-PCT could be a useful diagnostic marker for differentiating diagnosis of NF from cellulitis.

Kawasaki disease (KD) is a febrile disease of childhood characterized by systemic vasculitis that can lead to coronary artery lesions (CAL). This was a prospective cohort study to determine the levels of the pentraxin 3 (PTX3), soluble CD24-Subtype (Presepsin) and N-terminal pro-brain natriuretic peptide (NT-pro BNP) in consecutive KD patients. From January 2013 to March 2015, all patients with KD admitted to Aichi Medical University Hospital who provided consent had their plasma saved before IVIG administration. In total, 97 cases were registered. 22 cases of incomplete KD were excluded from the outcome analysis. The total 75 cases were used for statistical analyses. A PTX3 threshold of >7.92 ng/ml provided a specificity of 88.5 %, a sensitivity of 94.4 %, and a likelihood ratio as high as 15.92 for the diagnosis of KD compared with febrile non-KD controls. Although an echocardiographic diagnosis of CAL in the early course of the disease was confirmed in 24 cases, it was not in the remaining 51 cases. Neither NT-proBNP nor Presepsin had statistical significance for the prediction of the echocardiographic CAL diagnosis. Only PTX3 was significantly predictive of the echocardiographic CAL diagnosis (p=0.01). The PTX3 level was significantly higher in the intravenous immunoglobulin (IVIG) non-responders (45.9±7.45) than in the IVIG responders (17.0 ± 1.46 ng/ml) (p< 0.001). The PTX3 level also correlated with the number of IVIG treatment courses needed to resolve fever (R² =0.64). Persistent CAL (pCAL) formation was observed in three cases; one of aneurysm only and two aneurysms with dilatations. The patients with pCAL had significantly higher PTX3 levels (85 ± 8.4 ng/ml) than patients without pCAL (22 ± 2.2 ng/ml) (p< 0.0001). In terms of pCAL prediction, the area under the curve (AUC) of receiver operating characteristic ROC curve of PTX3 was 0.99, and it was significantly greater than that of Presepsin (0.67) or NT-proBNP (0.75). PTX3 is a soluble pattern recognition molecule that acts as a main component of the innate immune system. These data suggest that PTX3 can be utilized as a definitive biomarker for the prediction of IVIG resistance and subsequent CAL formation in patients with KD.

Background Only a single meta-analysis has reported the clinical benefit of fluoroquinolones (FQs) for Legionella pneumonia; however, there is no robust data available to confirm this result, based on current guidelines. Methods We performed a systematic review and meta-analysis comparing FQs with macrolides (MCs) on their efficacy and safety in Legionella pneumonia, using studies published until January 2020. The outcomes included mortality (overall; 30-day), clinical cure, time to apyrexia, length of hospital stay, and adverse events. Results Five RCTs and twelve retrospective studies were identified. Clinical cure was comparable between the treatment groups (risk rate (RR) 1.07, 95% confidential interval (CI) 0.86–1.31). Mortality was significantly higher for MCs than for FQs (overall, odd rate (OR) 0.59, 95% CI 0.35–0.98; 30-day, OR 0.41, 95% CI 0.20–0.85). FQs significantly reduced the length of hospital stay, compared to MCs (mean difference −3.58, 95% CI -5.48–1.69). Other outcomes were not significantly different between the treatment groups (time to apyrexia; mean difference −1.83, 95% CI -5.15–1.5, adverse events; OR 0.61, 95% CI 0.33–1.15). In subgroup analyses, levofloxacin significantly reduced the length of hospital stay over two specific MCs (azithromycin and clarithromycin) (mean difference −3.03, 95% CI -5.33–0.72), whereas mortality was not significantly different between the treatment groups (overall, OR 0.49, 95% CI 0.19–1.24; 30-day, OR 0.38, 95% CI 0.13–1.13). Conclusions FQs exhibited superior effects in terms of mortality and length of hospital stay in Legionella pneumonia. These results support current guidelines recommending FQs for the treatment of Legionella pneumonia.

The novel coronavirus disease 2019 (COVID-19) is diagnosed by positive result of reverse transcription polymerase chain reaction (RT-PCR) for the novel coronavirus. We concluded that cycle threshold value (Ct-value) of real-time RT-PCR (rRT-PCR) assay could decrease as patients recover. Results of rRT-PCR assay could remain positive among asymptomatic patients for longer than 2 weeks. The discharge criteria of COVID-19 patients using a negative result of rRT-PCR should be reconsidered.

We conducted a nationwide retrospective study in Japan to evaluate the effectiveness of oral amoxicillin or ampicillin as alternatives to injectable benzathine penicillin G for treating pregnant women with syphilis and preventing congenital syphilis (CS). We investigated 80 pregnant women with active syphilis treated with amoxicillin or ampicillin during 2010–2018. Overall, 21% (15/71) had pregnancies resulting in CS cases, and 3.8% (3/80) changed therapies because of side effects. Among 26 patients with early syphilis, no CS cases occurred, but among 45 with late syphilis, 15 (33%) CS cases occurred. Among 57 patients who started treatment >60 days before delivery, 8 (14%) had CS pregnancy outcomes. We found oral amoxicillin potentially ineffective for preventing CS cases among pregnant women with late syphilis but potentially effective in those with early syphilis. Prospective studies are needed to definitively evaluate the efficacy of amoxicillin for the treatment of pregnant women with syphilis to prevent CS.

The current guidelines suggest that hospital rooms previously occupied with Clostridioides difficile infection (CDI) patients should be decontaminated with recommended decontamination methods because C. difficile can persist on surfaces despite adherence to the recommended procedures. Recently, ultraviolet (UV) light and hydrogen peroxide have increasingly been used as innovative decontamination methods. Hence, we conducted a systematic review and meta-analysis to investigate which decontamination methods are effective in reducing environmental C. difficile contamination. We systematically searched the EMBASE, PubMed, CINAHL, Scopus, and Ichushi until March 11, 2021. We evaluated the efficacy of decontamination methods in terms of the frequency of C. difficile contamination on high-touch surfaces in hospital rooms and the incidence of hospital-acquired C. difficile infection. Among the 15 studies retrieved in our meta-analysis, eight evaluated decontamination methods with the frequency of C. difficile detection among samples after disinfection procedures, and eight reported the number of hospital-acquired CDI cases. Pooled analysis indicated that hydrogen peroxide significantly reduced the frequency of environmental C. difficile contamination, compared with hypochlorite (odds ratios [OR]: 0.12; 95% confidence interval [CI]: 0.07–0.23). Additionally, hydrogen peroxide reduced the incidence of hospital-acquired CDI compared to other methods (OR: 0.52; 95% CI: 0.28–0.96). Decontamination with UV significantly reduced the incidence of hospital-acquired CDI compared to hypochlorite (OR 0.52, 95% CI 0.28–0.96). The use of hydrogen peroxide and UV can help prevent environmental C. difficile contamination and transmission in healthcare facilities.

At present, vancomycin (VCM) and metronidazole (MNZ) are used for the first-line standard treatment of Clostridioides difficile infection (CDI). However, their differential use has not been sufficiently investigated. In this study, a meta-analysis on differences in the efficacy for CDI between VCM and MNZ was performed. Reports of randomized controlled studies using VCM or MNZ to treat CDI were surveyed. Meta-analysis was performed using the Mantel-Haenszel method and random-effects model, and the risk ratio and 95% confidence interval were calculated. Excluding overlapping reports, 1043 reports were extracted and 5 randomized controlled studies were extracted. There was no difference in therapeutic effects for CDI between VCM and MNZ (RR = 1.08, 95% CI (0.99–1.17), p = 0.09, I2 = 37%). On subgroup analysis by the severity, there was no difference in the clinical effects for CDI between VCM and MNZ in non-severe cases (risk ratio: 1.09, 95% confidence interval: 1.00–1.19, p = 0.06), but the clinical effects of VCM were significantly higher than those of MNZ in severe cases (risk ratio: 1.19, 95% confidence interval: 1.02–1.39, p = 0.03). No significant difference was noted in the recurrence rate, incidence of adverse event, time to exhibit therapeutic effects, or judgment of the bacteriological effects. As the therapeutic effects of VCM were superior in severe CDI cases, VCM should be considered first in severe cases.

Background Vancomycin has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants, while it is difficult to adjust blood concentration. Linezolid is also effective for Gram-positive infection, and is not necessary to monitor drug blood concentration. Primary objective of this study was to compare the safety of linezolid and vancomycin in infants and neonates for resistant Gram-positive infections. Methods In total, 68 patients [linezolid group (32 patients); vancomycin group (36 patients)] treated with antimicrobials at Aichi Medical University Hospital between April 2014 and March 2017. Investigation items were as follows; sex, age, gestational age, birth weight, body weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, serum levels of vancomycin, disease type, concomitant medications, clinical isolates, adverse effects during antimicrobial treatment, antimicrobial susceptibility of isolated Gram-positive bacteria. Results Any substantially abnormal laboratory values were admitted in linezolid 40.6% (13/32) and vancomycin 41.7% (15/36) groups, respectively (p = 0.93). Platelet count was significantly decreased in only linezolid group (p = 0.03). Any adverse events during antimicrobial treatment were admitted in linezolid 46.9% (15/32) and vancomycin 58.3% (21/36) groups, respectively (p = 0.34). Conclusion There were no notable differences in safety of linezolid and vancomycin groups even in neonates and infants. However, platelet count was significantly decreased in only linezolid group. The careful monitoring of platelet count would be required for infants and neonates receiving linezolid treatment.

Introduction Staphylococci is the most commonly isolated bacteria in blood cultures (BC), and is mostly regarded as contamination. However, the clinical relevance and characteristics of CNS other than Staphylococcus epidermidis (Non-SE-CNS) is still unknown. Methods For the purpose of clarifying the epidemiology and clinical significance of Non-Se-CNS infections, we retrospectively evaluated BC isolates of Non-Se-CNS at our institute from May 2013 to March 2017. Infections were defined as true bacteremia if (1) two or more positive BCs of the same species were present (or detection of the same species in another clinically relevant sample), (2) the patient had clinical symptoms as outlined in the Centers for Disease Control and Prevention's definition of primary blood stream infection8 and the symptoms or markers of inflammation (e.g., fever, symptoms, white cell counts, C-reactive protein, or procalcitonin) were improved after pathogen-directed therapy (e.g. either antibiotic therapy and/or removal of the foreign body in the case of catheter-related blood stream infections suspected) and (3) without any other infection. Results During the period, 279 patients with BC positive for Non Se–CNS were identified. 44 patients were excluded, either due to missing data or multiple pathogens in the same BC. Among the remaining 235 patients, 67 (29%) were categorized as true bacteremia (n = 43) or possible infections (n = 24). Resistance rate to methicillin among Non-SE-CNS is about 60%, which is lower than those among S. epidermidis of 78%. Conclusion About 30% of Non-Se-CNS isolates were clinically relevant in our study. Antibiotic susceptibility of Non-SE-CNS is quite different than those of S. epidermidis.

The Japanese Respiratory Society newly updated the prognostic guidelines for pneumonia in 2017. Quick Sequential Organ Failure Assessment (qSOFA) and Sequential Organ Failure Assessment (SOFA) score are used to evaluate the severity of pneumonia and to select the therapy for pneumonia. This is a retrospective study at Aichi Medical University hospital from January to December of 2016 to investigate the accuracy and usefulness of qSOFA and SOFA score in evaluating the severity and prognosis of healthcare-associated pneumonia (HCAP). A total of 81 HCAP patients were enrolled in this study. Both the 30-day and in-hospital mortality were 7.5% (6/81). qSOFA≧2 was in 33/78 patients (42%) and

Recurrent Clostridium difficile infection is considered as a significant health care burden. The global study (MODIFY II) of antibody treatment (bezlotoxumab) for the prevention of recurrent C. difficile infection includes Japanese patients (95 subjects); The aim of this subgroup analysis is to report the data obtained from Japanese patients. Patients with C. difficile infection receiving standard of care antibiotic treatment and a single infusion of bezlotoxumab 10 mg/kg, actoxumab 10 mg/kg + bezlotoxumab 10 mg/kg or placebo. Recurrent C. difficile infection through Week 12 was evaluated. In the Full Analysis Set (93 subjects), 91% were older than 65 years of age and 93% were hospitalized at the time of study entry. The standard of care antibiotic for C. difficile infection was metronidazole for 57 subjects and vancomycin for 36 subjects. The recurrent C. difficile infection rate was 46% in the placebo, 21% in the bezlotoxumab (p = 0.0197) and 28% in the actoxumab + bezlotoxumab group. No additive recurrent C. difficile infection-reducing effect with the addition of actoxumab was demonstrated. There were no events representing safety concern in bezlotoxumab. Among 54 clinical isolates of C. difficile as a baseline culture in Japanese patients, the common ribotypes were 052 (28%), 018 (19%), 002 (15%) and 369 (9%). It showed distinctly different distribution from that in the United States and Europe. The superior effect of bezlotoxumab 10 mg/kg in the prevention of recurrent C. difficile infection suggests that the agent will be useful in the rapidly aging Japanese society.

Objective From November 24 to December 9, 2013, an outbreak of the influenza (flu) A (H3) virus occurred in a tertiary-care university hospital (1,014 beds). We herein report the prophylactic effect of anti-flu agents for controlling the flu outbreak. Methods We administered pre- or post-exposure prophylaxis with anti-flu agents in flu outbreak. To test the effectiveness of prophylaxis in a flu outbreak, we used the posterior mean of the reproductive value during the pre- and post-intervention period. We also simulated the probability distribution of new flu cases. We performed an analysis to quantify the strength of the intervention effect. Results A total of 97 people were diagnosed with flu before the intervention, and 7 were diagnosed after the intervention. A molecular analysis of the flu virus revealed that this outbreak was due to the flu A (H3) virus. A total of 3,702 people received prophylaxis. There was a significant reduction in the reproductive value from 1.89 [95% confidence interval (CI), 1.59 to 2.24] to 0.65 (95% CI, 0.02 to 1.00) after the intervention (p

The aim of this study was to investigate the association between vancomycin trough level and clinical outcomes (mortality and nephrotoxicity) among infected paediatric patients with Gram-positive pathogens. We systematically searched the Scopus, EMBASE, Cochrane Central Register of Controlled Trials, PubMed and CINAHL databases up to March 2020. A total of seven retrospective cohort or case-control studies were included to compare clinical effects and safety: three studies set the threshold of vancomycin trough level at 10 mg/L and the others set it at 15 mg/L. Our analysis showed that vancomycin trough level of 10-15 mg/L was associated with significantly lower mortality [10 mg/L vs. ≥10 mg/L, odds ratio (OR) = 3.21, 95% confidence interval (CI) 1.74-5.91; and15 mg/L vs. ≥15 mg/L, OR = 0.31, 95% CI 0.10-0.95). The high vancomycin trough group (≥10 mg/L or ≥15 mg/L) showed a higher incidence of nephrotoxicity (10 mg/L vs. ≥10 mg/L, OR = 0.06, 95% CI 0.03-0.12; and15 mg/L vs. ≥15 mg/L, OR = 0.28, 95% CI 0.12-0.65). This is the first meta-analysis to reveal the optimal therapeutic range of vancomycin trough level in children. Our findings strongly suggest a superior benefit of vancomycin trough of 10-15 mg/L for paediatric patients.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 37.2% 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 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

In recent years, Streptococcus anginosus group (SAG) bacteria are becoming increasingly recognized as important pneumonia-causing pathogens. Although several small studies have been reported, the features of SAG pneumonia remain unclear, because the identification of SAG from sputum cultures is not routinely performed in most microbiology laboratories. The aim of this study was to elucidate the clinical characteristics of SAG pneumonia.This was a retrospective case-control study utilizing data obtained in our hospital between September 2009 and June 2016. We investigated 31 patients with SAG pneumonia (PWP), and also assessed the difference between the 31 PWP and 37 patients without pneumonia (PWOP) in whose sputum SAG was detected.Seventy-one percent of the patients were men and the median age was 78 years in the PWP. Univariate analysis indicated that the PWP were significantly more often a bed-ridden (p 0.01) with comorbid aspiration than were the PWOP (p 0.05). Among the PWP, nursing and healthcare-associated pneumonia (NHCAP) was the more common type of pneumonia (54.8%). S. anginosus was detected significantly more frequently in sputum cultures of PWP than PWOP (p 0.01), and multiple pathogens were detected more frequently in PWP (p 0.01). Streptococcus constellatus was the most frequently detected pathogen in patients with a single bacterial infection. Empyema was observed only in patients with multiple bacteria.SAG should be recognized as important causative pathogens of pneumonia, particularly among elderly patients with underlying disease associated with aspiration. NHCAP was the more common type of SAG pneumonia in this study.

Background Bacillus cereus sometimes causes central nervous system infection, especially in compromised hosts. In cases of meningitis arising during neutropenia, CSF abnormalities tend to be subtle and can be easily overlooked, and mortality rate is high. We report a survived case of B. cereus meningitis/brain abscess in severe neutropenia, presenting as immune reconstitution syndrome. Case presentation A 54-year-old Japanese female with acute myelogenous leukemia developed B. cereus bacteremia and meningitis during consolidation chemotherapy. At the onset, she presented with mild meningism. She had marked leukocytopenia (WBC Conclusions With early diagnosis and prompt initiation and of antibiotics, the case was successfully treated without any sequelae. It is important to remember that, even under optimal antimicrobial therapy, bone marrow recovery can cause transient reaggravation of the disease. In such cases, timely and appropriate evaluation should be done to make the clinical decision to change, continue, or intensify treatment.

While community-onset pneumonia patients such as community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) have several risk factors of Clostridium difficile infection (CDI), prognostic guidelines for pneumonia never mention the occurrence of CDI following treatment for pneumonia. For the purpose of examining the occurrence and prevalence of CDI, we reviewed all community-onset pneumonia patients who were admitted to our institute during the study period. A total of 406 patients were enrolled in this study. Among them, 257 patients (63%) were male, and the median age was 79 years (range 19-103 years). Surprisingly, 155 CAP (88%) and all HCAP (100%) patients had one or more risk factors for CDI. Furthermore, 70 CAP (40%) and 157 HCAP (69%) patients had more than 3 risk factors for CDI. Despite these facts, probiotic medication for prevention of CDI were prescribed for 12 (7%) CAP and 15 (7%) HCAP patients as the initial treatment. Finally, 3% and 9% of CAP and HCAP patients had CDI after completing the treatment for pneumonia. Regarding the duration of antibiotic therapy, 146 CAP (82%) and 176 HCAP (77%) patients received it for longer than 8 days, even though bacteremia was not confirmed in those patients. In addition, 27 CAP (15%) and 26 HCAP (11%) patients received a combination antibiotic therapy as an initial treatment. They seemed to be unnecessary. Physicians should acknowledge community-onset pneumonia has several risk factors for CDI, and should avoid a longer than necessary antibiotic therapy and unnecessary combination antibiotic therapy for pneumonia patients with risk factors for CDI.

This retrospective cohort study aimed to determine the incidence rates of and risk factors for recurrent Clostridioides difficile infection (rCDI) in Japan using a claims database. Inpatients of any age with ≥1 record of C. difficile infection (CDI) during the study period (January 2012-September 2016) were analyzed. We estimated the incidence rate of health care onset, health care facility associated (HO-HCFA) primary CDI and HO-HCFA rCDI for each of the first to fifth recurrences. Risk factors for the first recurrence were investigated using a univariate, and subsequently, a multivariable Cox regression model. The incidence rates (95% confidence interval [CI]) of CDI and HO-HCFA CDI were 2.43 (2.40-2.46) and 1.26 (1.24-1.28) cases per 10,000 inpatient-days, respectively. Among the 11,287 inpatients with ≥1 HO-HCFA CDI, 1424 patients had ≥1 recurrent episode (12.6% [95% CI 12.0-13.2]). The rCDI incidence rates consistently increased, with the number of recurrences ranging from 29.2 to 181.8 cases per 10,000 inpatient-days. The multivariable analysis revealed five risk factors (hazard ratio [95% CI]): age ≥65 years (vs.65 years; 65-74 years, 1.275 [1.048-1.551]; 75-79 years, 1.612 [1.315-1.975]; ≥80 years, 2.110 [1.776-2.507]); cephalosporin use both before (vs. without cephalosporin; 1.241 [1.098-1.402]) and during the primary CDI (vs. without cephalosporin; 1.137 [1.011-1.279]); higher number of comorbidities (vs. ≤10 comorbidities; 11-14 comorbidities: 1.336 [1.131-1.580]; 15-20 comorbidities: 1.433 [1.219-1.685]; ≥21 comorbidities: 1.310 [1.099-1.561]); and gastrointestinal surgery (vs. without surgery; 0.823 [0.701-0.965]). In conclusion, CDI recurred in some Japanese patients, and the incidence rates increased with the number of recurrences. Special care is needed in patients aged ≥65 years, those with a higher number (10) of comorbidities, and those who have received cephalosporin before or during the primary CDI.