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While acute empyema is a critical infectious disease showing a high mortality rate, there are no prognostic tools to evaluate the disease severity and prognosis for patients. We conducted a retrospective cohort to determine whether quick Sequential Organ Failure Assessment (qSOFA) and SOFA score can predict the disease severity and prognosis of acute empyema. A total of 53 patients were enrolled in the study. The mean age was 69 years and 41 patients (77%) were male. Twenty-two patients (42%) had multiple underlying diseases with the Charlson comorbidity index ≥3. The-30 days, and in-hospital deaths were 7 (13%) and 10 (19%), respectively. The area under the ROC curve of SOFA score and CCI for 30-day and in-hospital deaths were 0.814 (p = 0.073) and 0.752 (p = 0.082), 0.848 (p = 0.07) and 0.762 (p = 0.011), respectively. Univariate analysis showed that qSOFA ≥2 and SOFA score ≥2, isolation of potentially drug-resistant (PDR) pathogen, high CCI (≥3), performance status of 2-4, surgical intervention, and anaerobic bacteria involvement were prognostic factors. Of these, multivariate logistic regression analysis showed that qSOFA ≥2 and SOFA score ≥2 (p = 0.011), isolation of PDR pathogen (p = 0.005), and high CCI (≥3) (p = 0.015) were independently poor prognostic factors. We concluded that qSOFA and SOFA scores could predict the disease severity and prognosis in acute empyema. Additionally, isolation of PDR pathogens and high CCI could be poor prognostic factors for patients.

Fidaxomicin (FDX) has received considerable attention as a novel therapeutic alternative agent to vancomycin (VCM) for Clostridioides difficile infection (CDI). However, the superiority and efficacy profile of FDX are not sufficiently determined by high-quality evidence. This study aimed to clarify the superiority of FDX for CDI treatment through a systematic review and meta-analysis.We conducted a meta-analysis of randomized controlled trials (RCTs) which evaluated the efficacy and safety of FDX and VCM in patients with CDI. Electronic databases (PubMed, Cochrane Library, Web of Science, and Clinicaltrials.gov) were searched for studies published until October 15, 2021. The primary endpoint was global cure. The secondary endpoints were clinical cure, recurrence, and adverse event. Risk ratios (RRs), risk differences (RDs), and 95% confidence intervals were calculated using Mantel-Haenszel random-effects model. The risk of bias was assessed using Cochrane Handbook for Systematic Reviews of Interventions and Assessment Criteria.Six RCTs were included in this meta-analysis. Compared to VCM, FDX was associated with significantly higher global cure rates (RR = 1.18, P 0.00001; RD = 0.11, 95% CI = 0.07-0.16). In addition, clinical cure rates were comparable between FDX and VCM (P = 0.31). FDX was associated with significantly lower recurrence rates compared to VCM (RR = 0.59, P 0.0001). In addition, adverse event rates were not significantly different between the drugs (P = 0.41).FDX achieves significantly higher global cure rates and lower recurrence rates and is comparable to VCM in clinical cure rates and adverse event rates in patients with CDI. Collectively, FDX is superior to VCM as a therapeutic agent for CDI.

Invasive extraintestinal pathogenic Escherichia coli (ExPEC) disease (IED), characterised by sepsis and bacteraemia, is a major global healthcare concern worsened by emerging multidrug resistant (MDR) strains. The development of multivalent prophylactic vaccines targeting E. coli strains of IED-associated O-serotypes could address this. A better understanding of O-serotype distribution is required for this purpose. Here, we characterised O-serotype prevalence and drug resistance among ExPEC bacteraemia isolates in Japan.E. coli blood isolates from patients aged ≥60 years with bacteraemia were obtained from a retrospective surveillance study in Japan (2015-2017). O-serotyping was performed by agglutination; for isolates non-typeable by agglutination, O-genotyping was performed. Antimicrobial susceptibility was evaluated by broth microdilution using a 21-antibiotic panel. The frequency of drug resistant (DR) isolates was evaluated by antimicrobial susceptibility testing.Of 401 ExPEC bacteraemia isolates evaluated, the most prevalent O-serotype (≥1%) was O25 (28.7% [n = 115]), followed by O1 (14.2% [n = 57]), O2 (8.5% n = 34]), O6 (5.5% [n = 22]), O75, O18, O13, O16, O15, O4, O46/O134, O86, O8 and O83 (each5% prevalence). These 14 O-serotypes accounted for 81.5% of isolates collected. In total, 19% (n = 77) of isolates were DR ≥ 3, of which 59.7% were O25. Fluoroquinolone-resistance among all and O25 isolates was most prevalent (35.7% and 84.3%, respectively). Almost all (98%) isolates identified as O25 were of subtype O25B.E. coli serotype O25B showed the highest prevalence and highest multidrug resistance among ExPEC bacteraemia isolates from patients ≥60 years in Japan. Our data may inform development of multivalent glycoconjugate vaccines to prevent IED.

The coronavirus 2019 (COVID-19) pandemic is a health and economic crisis. It has also highlighted human relational problems, such as racism and conflicts between nations. Although vaccination programs against the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) have started worldwide, the pandemic is ongoing, and people are struggling. The mechanism of disease severity in COVID-19 is multifactorial, complicated, and affected by viral pathogenesis. For example, monocyte dysfunction due to aging and respiratory and gut dysbiosis influence the host's immunity against SARS-CoV-2 including helper T-cell imbalance and viral clearance reduction, leading to accelerated disease progression in older patients or those with underlying diseases. The different immune responses against SARS-CoV-2 also contribute to various radiological findings, including that of acute respiratory distress syndrome, which is associated with high mortality, especially in patients susceptible to disease progression. We aimed to review the pathophysiological mechanisms involved in COVID-19, with emphasis on the altered microbiome in the lung and gut, and the different radiological findings in different patient groups, such as younger adults and pregnant women.

This survey of bile replacement (BR) was conducted on patients with external biliary drainage to assess the current status of indication and implementation protocol of BR with special reference to infection control.A 12-item questionnaire regarding the performance of perioperative BR was sent to 124 institutions in Japan.BR was performed in 29 institutions, and the indication protocol was introduced in 19. BR was performed preoperatively in 11 institutions, pre- and postoperatively in 12, and postoperatively in 6. The methods used for BR administration included oral intake (n = 10), nasogastric tube (n = 1), enteral nutrition tube (n = 3), oral intake and enteral nutrition tube (n = 6), oral intake or nasogastric tube (n = 2), nasogastric tube and enteral nutrition tube (n = 2), and oral intake or nasogastric tube and enteral nutrition tube (n = 5). In 10 of 29 institutions, isolation of multidrug-resistant organisms and a high bacterial load were considered contraindications for the use of BR. Seven institutions experienced environmental contamination.Given the different implementation of BR among institutions, the appropriate indication and protocols for BR should be established for infection control.

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 Patients with nursing and healthcare-associated pneumonia (NHCAP) commonly receive empiric antibiotic therapy according to the guideline's recommendation corresponding to the patient's deteriorated conditions. However, it is unclear whether guideline-concordant treatment (GCT) could be effective or not. Patients and methods To evaluate the efficacy and validity of GCT according to the current guideline for pneumonia, we conducted this retrospective study. NHCAP patients who were admitted to our institute between 2014 and 2017 were enrolled. Based on the initial antibiotic treatment, these patients were divided into two groups, the GCT group (n = 83) and the non-GCT group (n = 146). Propensity score matching (PSM) was used to balance the baseline characteristics and potential confounders between the two groups. After PSM, patients’ characteristics, microbial profiles, and clinical outcomes were evaluated. Results Both groups were well-balanced after PSM, and 78 patients were selected from each group. There were no differences in patients’ characteristics or microbial profiles between the two groups. As for outcomes, there were no differences in 30-day, in-hospital mortality rate, duration of antibiotic treatment, or admission. The severity of pneumonia was more severe in patients with the GCT group than those with the non-GCT group. Anti-pseudomonal agents as initial treatment were more frequently seen in patients with the GCT group than those in the non-GCT group. Conclusion Unlike previous studies, GCT's recommendation for management of pneumonia by the JRS in 2017 would appear to be valid and does not increase the mortality rate.

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.

A high incidence of genital infections, such as vulvovaginal candidiasis, has been reported in patients with diabetes treated with sodium-glucose co-transporter type 2 inhibitors. This is because Candida growth and virulence are enhanced in high glucose environments. Our previous study demonstrated that the adhesive interaction between Candida complement receptors and a ligand on vaginal epithelial cells (intracellular adhesion molecule-1: ICAM-1) is a factor for Candida albicans colonization, and the high ICAM-1 expression by vaginal epithelial cells exposed to high glucose conditions increases C. albicans adhesion. In this study, we examined the effect of a sodium-glucose co-transporter type 2 inhibitor, empagliflozin, on Candida glabrata adhesion to human cells (VK2/E6E7). There was no significant difference among four conditions that contained empagliflozin at various concentrations. We demonstrated that empagliflozin does not affect C. glabrata adhesion to VK2/E6E7 cells.

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.

Background Presepsin (soluble CD14 subtype) is a novel biomarker of sepsis used for early diagnosis. Originally, CD14 is known as the pattern recognition receptor for the lipopolysaccharide (LPS)/LBP complexes, and the diagnostic value of this molecule for gram-positive bacteria, which contain less amount of LPS, is uncertain. To confirm its effectiveness in the diagnosis of bacteremia caused by gram positive bacteria, and to evaluate the interspecies difference of presepsin production against various bacterial strains, we conducted an in vitro assay to evaluate presepsin levels in response to five Gram negative and four Gram positive bacteria. Results Whole blood was yielded from five healthy volunteers and co-cultured with bacterial strains at 37 °C for 4 h. Twenty seven clinical isolates of nine species (E. coli, K. pneumoniae, E. cloacae, P. aeruginosa, S. maltophilia, S. aureus, S. pyogenes, B. cereus, and C. striatum) derived from blood cultures of non-neutropenic bacteremia patients were used. Culture supernatants were harvested and presepsin levels were measured. The presepsin level in the gram-negative bacteria 273 (218–352) pg/mL was significantly higher than in the gram-positive bacteria 200 (143–275) pg/mL (p = 0.0002). The presepsin levels were significantly lower in C. striatum, in comparison to other bacteria, and S. pyogenes showed similar results. And the presepsin levels in P. aeruginosa were significantly lower compared to E. cloacae, K. pneumoniae, and S. aureus. Conclusions Presepsin production can also be evoked by gram-positive bacteria, and interspecies differences of presepsin response may exist, which should be considered in the diagnosis of sepsis, especially in certain gram-positive bacteremia such as S. pyogenes or C. striatum.

This study investigated the epidemiology of adult patients with bacteremia caused by seven major gram-negative bacteria during a year at four university hospitals in Japan. Of the 438 cases included, Escherichia coli (247 patients) was the most frequently isolated pathogen, followed by Klebsiella species (89 patients), Enterobacter species (31 patients), Pseudomonas aeruginosa (29 patients), Bacteroides species (19 patients), Acinetobacter species (12 patients) and Stenotrophomonas maltophilia (11 patients). The overall, crude in-hospital mortality was 16.4%, ranging from 9.7% with Enterobacter species to 54.5% with S. maltophilia. Community- and hospital-acquired bacteremia accounted for 52.5% and 47.5%, respectively. Enterobacteriaceae were isolated from 93.0% of patients with community-acquired bacteremia, whereas non-fermenting bacteria were isolated from 21.6% of patients with hospital-acquired bacteremia. Of the 423 patients analyzed, 86.8% and 13.2% were monomicrobial and polymicrobial infections, respectively, and their in-hospital mortalities were 13.9% and 30.4%, respectively. Although carbapenem-resistant Enterobacteriaceae were not detected, extended-spectrum β-lactamase (ESBL) production was seen in 24.3% of E. coli and 6.7% of Klebsiella species, respectively. E. coli producing ESBL showed high resistance rates to fluoroquinolones (approximately 90%), in contrast to non-producing-E. coli (approximately 21%). The susceptibilities to carbapenems and fluoroquinolones were approximately 80% for P. aeruginosa, whereas all Acinetobacter species were susceptible to these antibiotics. Bacteroides species showed 100% susceptibility to piperacillin/tazobactam and carbapenems, but only 47.4% were susceptible to clindamycin. Further studies, as well as continued surveillance, are required to determine the appropriate therapeutic strategy for gram-negative bacteremia.

Background Carbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy. Material and methods Total eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate. Results The combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log10 cfu/mL, p Conclusion Our results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.

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.

The results from the phase 3 study that evaluated the efficacy and safety of tedizolid phosphate, an oxazolidinone drug, for the treatment of gram-positive ventilated hospital-acquired bacterial pneumonia (vHABP)/ventilator-associated bacterial pneumonia (VABP) compared with linezolid (VITAL study), have been previously reported. We conducted a subgroup analysis to report the data obtained from Japanese patients enrolled in this study.Patients aged ≥18 years with vHABP/VABP likely to be caused by gram-positive cocci were randomized 1:1 to tedizolid phosphate 200 mg once daily for 7 days or linezolid 600 mg twice daily for 10 days. In both treatment groups, patients with concurrent gram-positive bacteremia were treated for 14 days. Primary efficacy endpoints were day 28 all-cause mortality (ACM) and investigator-assessed clinical response at test-of-cure (TOC) in the intention-to-treat population. Safety outcomes included assessment of treatment-emergent adverse events.Fifty-three Japanese patients were randomized at received study drug (tedizolid, n = 28; linezolid, n = 25). Demographics and characteristics were generally similar between treatment groups. Rates of day 28 ACM were 10.7% and 20.0% with tedizolid and linezolid, respectively (difference, 9.3%; 95% CI, -10.1 to 28.7). Rates of investigator-assessed clinical cure at TOC were 78.6% and 72.0% with tedizolid and linezolid, respectively (difference, 6.6%; 95% CI, -16.7 to 29.8). Tedizolid phosphate was generally well tolerated and no new safety concerns were observed in the Japanese subgroup.The results from this subgroup analysis suggest generally favorable efficacy and safety of tedizolid in adult Japanese patients with vHABP/VABP. (ClinicalTrials.gov identifier: NCT02019420).

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.

Chronic endometritis is a persistent inflammatory condition of the endometrium that negatively affects pregnancy outcomes. The Centers for Disease Control and Prevention guidelines recommend oral antibiotic treatment for chronic endometritis. However, a recent randomized controlled trial concluded that it was unclear whether antibiotic treatment improved pregnancy outcomes. Hence, we performed a systematic review and meta-analysis to validate the impact of oral antibiotic treatments on pregnancy outcomes among patients with chronic endometritis.We systematically searched the PubMed, Scopus, Ichushi, CINAHL, and EMBASE databases until May 2021. We compared the pregnancy outcomes in patients with chronic endometritis with and without antibiotic treatment. We then focused on the implantation rate, intrauterine pregnancy rate, and live birth rate to evaluate pregnancy outcomes.Seven studies were included in the meta-analysis. Three hundred seventy-two patients were treated with antibiotics, while 1024 patients were not treated with antibiotics. Various antibiotic regimens were administered during the study period [14-21 days]. Antibiotic treatments for chronic endometritis did not increase the implantation rate (odds ratios [OR] 1.02, 95% confidence interval [CI], 0.78-1.33), intrauterine pregnancy rate (OR 1.08, 95% CI 0.72-1.63), or live birth rate (OR 1.13, 95% CI 0.65-1.97).Our meta-analysis proved that oral antibiotic treatment did not improve pregnancy outcomes in patients with chronic endometritis. Accordingly, further studies are needed to elucidate the treatment to improve pregnancy outcomes.

The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we describe a gut-lung axis mechanism and report that orally administered Clostridium butyricum (CB) enhances influenza virus infection resistance through upregulation of interferon (IFN)-λ in lung epithelial cells. Gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid (18-HEPE) promotes IFN-λ production through the G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activations. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression. This study finds a gut-lung axis mechanism and provides insights into the treatments and prophylaxis for viral respiratory infections.

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.

Rapid detection of β-lactamases is important in a recent situation where resistant bacteria are increasing. By using the drug susceptibility testing microfluidic device (DSTM), rapid screening of extended spectrum β-lactamases (ESBLs) and metallo-β-lactamases (MBLs) has become possible.β-lactams and β-lactamase inhibitors were pre-fixed in the DSTM for use. A bacterial suspension in Mueller-Hinton broth (McF 0.25) was introduced into the device, and the effects of β-lactamase inhibitor on morphological changes caused by β-lactam were evaluated after 3 h incubation.Clinical isolates genetically confirmed to produce β-lactamase were used. Of the 84 ESBL-producing strains, 80 strains (95%) turned to be ESBL positive, and five strains (6%) of them MBL were positive as well as ESBL. Four strains (5%) were negative for both ESBL and MBL. Of the 24 MBL-producing strains, 23 strains (96%) were positive for MBL. All the 43 AmpC-producing strains were negative for both ESBL and MBL. Of the 156 ESBL- and MBL-nonproducing strains, 155 strains (99%) were negative for both ESBL and MBL, and one strain was positive for ESBL. With this method, the detection sensitivity was 95% and the specificity was 100% for ESBL, whereas the detection sensitivity was 96% and the specificity was 98% for MBL. These results were not significantly different from the results of the disc diffusion method.The DSTM method allows rapid detection of β-lactamases in 3 h and may be a useful replacement for the disc diffusion method.

Despite the advance in antibiotics and widespread chest tube drainage, acute empyema still shows a high mortality rate, accounting for 10-25%. We experienced a case of acute empyema caused by A. hydrophila, which is extremely uncommon, and reviewed all previously published articles.A 76-year older man with a medical history of liver cirrhosis (LC) due to chronic hepatitis C and hepatic cell carcinoma was admitted to our institute. Elevated inflammatory reaction and effusions on chest CT were seen, and he was suspected of having acute empyema. Although an empiric antibiotic therapy of meropenem with chest tube drainage was performed as an initial treatment, he died within 8 hours of admission. Postmortem, both blood and left pleural fluid cultures yielded Aeromonas hydrophila. The final diagnosis was acute empyema caused by A. hydrophila. We reviewed previously reported empyema caused by Aeromonas species cases (4 A. hydrophila, and 1 A. veronii) in 4 previous reports written in English, including ours. Of 5, all were male, and the mean age was 52 years (range 27-76 years). All patients had LC due to alcohol or viral infections. As for antibiotics initially prescribed, third-generation cephalosporins were most frequently used in 3/5 (60%). Thoracentesis was performed in all patients (100%). As for prognosis, 2 (40%) survived, and 3 (60%) died.Physicians should be aware of the possibility of acute empyema caused by A. hydrophila among patients with chronic hepatic disease.

Background Rapid diagnosis of influenza is critical in preventing the spread of infection and ensuring patients quickly receive antiviral medication to reduce the severity and duration of influenza symptoms, whilst controlling the spread of the causative virus. In Japan patients are often administered anti-influenza medication following a positive rapid antigen detection test (RADT) result. However, the sensitivity of RADTs can lead to false negative results. The cobas® Influenza A/B Nucleic acid test for use on the cobas Liat® System (Liat) is a molecular point-of-care method that can provide a more sensitive alternative to RADTs for rapid influenza diagnosis and treatment. Methods In this prospective multicenter study, diagnostic performance of the Liat test was compared with RADTs in patients presenting with influenza-like-illness. Test performance was also assessed by time since symptom onset. Results Of 419 patients enrolled, 413 were evaluable for all designated tests. Most patients had type-A infection, and only one patient had influenza type B. In 413 patients, the sensitivity and specificity (95% CI) of the Liat test were 99.5% (97.2–99.9%) and 99.5% (97.4–99.9%), respectively, and were 79.7% (73.5–84.7%) and 95.4% (91.7–97.5%) for RADTs. For patients tested Conclusion Overall, compared with standard of care RADTs, the Liat test was more sensitive and specific in children and adults, particularly in the early stages of infection. Greater sensitivity can enable earlier diagnosis and may better inform appropriate antiviral treatment decisions.

Clostridioides difficile infection (CDI) is associated with a large burden of morbidity and mortality worldwide. Previous studies have developed models for predicting recurrence and mortality following CDI, but no machine learning predictive models have been developed specifically using data from Japanese patients.Using a database of records from acute care hospitals in Japan, we extracted records from January 2012 to September 2016 (plus a 60-day lookback window). A total of 19,159 patients were included. We used a machine learning approach, XGBoost, and compared it to a traditional unregularized logistic regression model. The first 80% of the dataset (by patient index date) was used to optimize model hyperparameters and train the final models, and evaluation was performed on the remaining 20%. We measured model performance by the area under the receiver operator curve and assessed feature importance using Shapley additive explanations.Performance was similar between the machine learning approach and the classical logistic regression model. Logistic regression performed slightly better than XGBoost for predicting mortality.XGBoost performed slightly better than logistic regression for predicting recurrence, but it was not competitive with existing published models. Despite this, a future machine learning-based application provided in a bedside setting at low cost might be a clinically useful tool.

The plasmid-mediated bacterial colistin-resistant gene, mcr, is of global concern in clinical healthcare. However, there are few reports of surveillance for mcr in Japan. The aim of this study was to assess the prevalence of colistin resistance by identifying nine mcr genes in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) isolates in Japan.A total of 273 ESBL and CRE clinical isolates were collected from patients in five tertiary hospitals from August 2016 to March 2017. Minimum inhibitory concentration (MIC) of colistin was measured using the microdilution method. Polymerase chain reaction (PCR) was performed to detect mcr-1 to mcr-9 genes in all strains. Whole-genome sequencing (WGS) analysis was conducted for any mcr-genes identified that had not been previously reported in patients from Japan.The rate of colistin resistance was 7.7% in all strains, with a higher rate in the CRE strains than in the ESBL-producing strains (20.4% versus 1.1%). The mcr-5 and mcr-9 gene were detected in one ESBL-producing Escherichia coli strain (1/273, 0.37%) and three CRE strains (3/273, 1.1%), respectively. As the ESBL-producing E. coli strain was the first clinical strain with mcr-5 in Japan, WGS analysis was performed for the strain. The sequence type of the mcr-5-positive strain was ST1642 and it carried two distinct plasmids, ESBL gene-carrying pN-ES-6-1, and mcr-5.1-carrying pN-ES-6-2.The results of this study showed that the frequency of colistin resistance and mcr-positive strains is not high in Japan. As the MIC for colistin was low in the mcr-5.1 and mcr-9 gene-positive strain, continuous monitoring of mcr genes is necessary.

Metronidazole (MNZ) is prescribed for the treatment of infection caused by anaerobic bacteria and protozoa. Metronidazole-induced encephalopathy (MIE) has been known to be a side-effect, although its onset ratio is unclear. However, to the best of our knowledge, MIE associated with hyperbaric oxygen therapy (HBO) has not been previously reported. Here, we present the case of a 68-year-old man with mandibular osteomyelitis who received metronidazole for 49 days and received five times HBO therapy. He visited our hospital for evaluation and treatment of peripheral neuropathy, speech disturbance, nausea, and disturbance of gait after 47 days of initiating metronidazole treatment. Brain magnetic resonance imaging revealed hyperintense lesions in the cerebellar dentate nuclei, which was consistent with MIE. The patient's ataxic symptoms improved in 15 days after the discontinuation of MNZ. This is the first report demonstrating case of MIE could be related with HBO, as far as we had searched.

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.

We compared the susceptibility of six commercially available antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, and amphotericin B) against 133 Candida bloodstream isolates between 2008 and 2013 at Aichi Medical University Hospital. C. albicans was the most common isolate, followed by C. parapsilosis, C. glabrata, and C. tropicalis. MIC90s of voriconazole against C. albicans, C. parapsilosis, and C. tropicalis were the lowest and that of micafungin against C. glabrata was the lowest among the agents tested. Of the 133 isolates, two strains were identified as drug-resistant. One was a fluconazole-resistant C. glabrata strain, in which the ATP-binding cassette (ABC) transporter gene expression was upregulated. The other was a micafungin-resistant C. glabrata strain, that had 13 amino acid substitutions in FKS1 and FKS2, including a novel substitution V1342I in FKS1 hotspot 2. We also evaluated the susceptibility of T-2307, a novel class of antifungal agents used in clinical trials, against the fluconazole- and micafungin-resistant C. glabrata strain; the MICs of T-2307 were 0.0039 and 0.0078 μg/mL, respectively. In conclusion, the incidence of bloodstream infection caused by drug-resistant Candida spp. was rare from 2008 to 2013 at our hospital. Of 133 isolates, only two strains of C. glabrata were resistant to azoles or echinocandins, that upregulated the ABC transporter genes or had novel FKS mutations, respectively.

Clostridioides difficile infection (CDI) often recurs. Approximately 25% of patients have recurrences after the initial treatment, and patients who have relapsed once are more likely to relapse. We aimed to identify the risk factors for initial CDI recurrence.We performed a retrospective survey of patient backgrounds and treatment-related factors. Risk factors were analyzed using single and multiple logistic regression analyses.A total of 134 patients were included in the study. Prophylactic probiotic use and nasogastric tube feeding were independent risk factors for the initial recurrence of CDI. Patients using prophylactic probiotics had significantly higher recurrence rates than those not using prophylactic probiotics.Prophylactic probiotic use and nasogastric tube placement may be risk factors for the initial recurrence of CDI. It is noteworthy that CDI that occurs during the use of prophylactic probiotics may be prone to recurrence.

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.

Considering the issues of shortage of medical resources and the invasiveness and infection risk involved in the collection of nasopharyngeal swab specimens, there is a need for an effective alternative test specimen for SARS-CoV-2 RNA detection. Here, we investigated suitability of saliva as a non-invasively obtained specimen for molecular detection of SARS-CoV-2 RNA in Japanese patients with COVID-19. In total, 28 paired clinical specimens of saliva and nasopharyngeal swabs were collected from 12 patients at various time points after symptom onset. Each specimen was assayed using reverse transcription real-time polymerase chain reaction (rRT-PCR) on the BD MAX open system using primers and probes targeting the N-gene. The saliva and nasopharyngeal swab specimens showed 19 and 15 positive results, respectively. No invalid (PCR inhibition) result was observed for any specimen. The qualitative results of each specimen obtained in the period immediately after symptom onset were similar. Three convalescent patients presented saliva-positive results, whereas their nasopharyngeal swabs were negative at four different time points, suggesting that saliva may be superior to nasopharyngeal swabs in terms of obtaining stable assay result of SARS-CoV-2. In conclusion, our results suggest that saliva can potentially serve as an alternative to nasopharyngeal swabs as a specimen for SARS-CoV-2 rRT-PCR. As saliva can be collected by patients themselves, it may be an effective way to overcome the shortage of personal protective equipment and specimen sampling tools.

Background Carbapenem-resistant Enterobacterales (CRE) and carbapenemase-producing Enterobacterales (CPE) are difficult to treat and are a serious public health threat. Nacubactam (NAC) is a novel non-β-lactam diazabicyclooctane β-lactamase inhibitor with in vitro activity against some Enterobacterales expressing classes of β-lactamases. Methods The antimicrobial efficacy of meropenem (MEM), cefepime (FEP), and aztreonam (ATM), each in combination with NAC, were assessed in vitro and in vivo against Klebsiella pneumoniae and Escherichia coli. Ten isolates, including CRE and/or CPE with β-lactamase genes, were used in this study. The relationship between phenotype and in vivo efficacy was assessed in a murine neutropenic thigh-infection model. Efficacy was determined by the change in bacterial quantity. Results The results of the in vitro study showed the minimum inhibitory concentrations of the combination of NAC with either MEM, FEP, or ATM in a 1:1 ratio were 2 to >128-fold lower than those of MEM, FEP, or ATM alone against CRE+ isolates. In addition, combinations of β-lactams and NAC administered in the murine thigh-infection model showed greater efficacy against CRE+/CPE+, CRE+/CPE-, and CRE-/CPE+ isolates harboring various β-lactamase genes (IMP-1, IMP-6, KPC, DHA-1, or OXA-48) compared with MEM, FEP, ATM, and NAC alone. Conclusion MEM, FEP, or ATM in combination with NAC showed potent in vivo antimicrobial activity in a murine thigh-infection model caused by K. pneumoniae and E. coli, including CRE and/or CPE isolates. These findings indicate that these combinations of β-lactams and NAC are potential candidates for the treatment of CRE and/or CPE infections.

This study aimed to evaluate the antimicrobial activity of a new quinolone, lascufloxacin, for the treatment of complicated pneumonia caused by Streptococcus pneumoniae and Prevotella intermedia using a neutropenic mice pneumonia mixed-infection model. In this study, one S. pneumoniae and four P. intermedia isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the reduction of the bacterial count comparatively to the non-treated mice (log10 colony forming units (cfu)/mL) obtained in the lungs of the treated mice after 24 h. Consequently, the bacterial densities of S. pneumoniae (KY-9) and P. intermedia (335) in the lungs of control animals were 8.20 ± 0.19 log10 cfu/mL and 5.26 ± 1.50 log10 cfu/mL, respectively. At human-simulated doses, lascufloxacin and levofloxacin showed high antimicrobial activities against not only S. pneumoniae (lascufloxacin: 1.88 ± 0.43 log10 cfu/mL, p

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.