Impact of Antibiotic Time-Outs in Multidisciplinary ICU Rounds for Antimicrobial Stewardship Program on Patient Survival: A Controlled Before-and-After Study.

The antimicrobial stewardship program (ASP) is an important quality improvement initiative that is recommended in the ICU. However, the shortage of infectious disease physicians in Japan has led to the need for simpler methods for implementing ASPs. We investigated whether antibiotic time-outs (ATOs) during multidisciplinary rounds as part of an ASP can improve patient survival and reduce the number of days of therapy (DOT) with antibiotics. DESIGN: Single-center controlled before-and-after study. SETTING: Medical/surgical ICU in a tertiary university medical center in Tokyo, Japan. PATIENTS: All patients 16 years old or older admitted consecutively in the ICU between October 2016 and March 2020. INTERVENTIONS: An intensivist-driven ICU multidisciplinary round was introduced in October 2016, and ATOs with ICU rounds were implemented in June 2018. ATOs were conducted 3, 7, and 14 days after initiation of antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the subdistribution hazard ratio (SHR) of survival to hospital discharge compared between multidisciplinary rounds (phase 1) and ATO during multidisciplinary rounds (phase 2) using the multivariable Fine-Gray model. The secondary outcomes were the SHR of survival to ICU discharge and the trends in the DOT with IV antibiotics per 1,000 patient-days between October 2016 and March 2020 by using interrupted time-series analysis. The number of patients in phases 1 and 2 was 777 and 796, respectively. The group that underwent ATO during multidisciplinary rounds showed a significant increase in the survival to hospital discharge in comparison with the multidisciplinary round-only group (SHR, 1.13; 95% CI, 1.02-1.25); however, the SHR of survival to ICU discharge showed no significant intergroup difference. The DOT with total IV antibiotics decreased after ATO implementation (change in intercept, -178.26; 95% CI, -317.74 to -38.78; change in slope, -7.00; 95% CI, -15.77 to 1.78). CONCLUSIONS: ATOs during multidisciplinary rounds are associated with improved patient survival and reduced DOT.

Clinical validation of an immunochromatographic SARS-Cov-2 IgM/IgG antibody assay with Japanese cohort.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a major health threat. To overcome COVID-19, appropriate diagnosis methods are urgently needed. The aim of this study was to clinically evaluate the colloidal gold immunochromatography assay for SARS-Cov-2 IgM/IgG antibody (Ab). METHODS: Patients confirmed COVID-19 (n = 51) were recruited prospectively from the Musashino Red Cross hospital and Tokyo Medical and Dental University Medical Hospital, between March and May 2020. And the analytical specificity was assessed with serum samples of patients without COVID-19 (n = 100) collected between August to September 2019 before SARS-CoV-2 was first reported in China. RESULTS: Among COVID-19 patients, a total of 87 serum samples were tested for SARS-Cov-2 IgM/IgG Ab assay. IgM was detected 71.0 %, 86.9 %, and 83.3 % at day8-14, 15-28, >29 after symptom onset and IgG was detected in 81.6 %, 87.0 %, and 94.4 %, respectively. The sensitivity of IgM and IgG Ab after day8 assay was significantly higher than before day7, respectively (p=0.0016, 0.0003). There were no positive results in 100 serum samples from patients without COVID-19. CONCLUSION: The SARS-Cov-2 IgM/IgG Ab assay had 79.7% / 86.1% sensitivity (the 8 days after from onset) and 100% specificity in this population.

Molecular epidemiologic and clinical analysis of Helicobacter cinaedi bacteremia in Japan.

BACKGROUND: Helicobacter cinaedi is an important pathogen that causes bloodstream infections. Owing to the challenges in its culture and identification, its clinical and bacterial characteristics remain unknown. Our study aimed to investigate the molecular epidemiology and antimicrobial susceptibility of H cinaedi. MATERIALS AND METHODS: From 2003 to 2016, we analyzed 16 non-repetitive H cinaedi strains, isolated from blood, at the medical hospital of Tokyo Medical and Dental University. Multilocus sequence typing was performed to analyze the genetic relationship across the different isolates. The minimum inhibitory concentrations (MIC) of antibiotics were determined by the agar dilution method. RESULTS: The median age of subjects in this study was 61 years (range, 18-84 years). The most common risk factors included the use of steroids (75.0%) and immunosuppressant drugs (37.5%). In addition, the most common symptoms of H cinaedi bacteremia included colitis (37.5%) and cellulitis (31.3%). The infection recurred in three of seven cases (42.8%) that underwent antibiotic therapy for <10 days. The strains were classified into five sequence types (ST), of which, ST 10 (43.8%) and ST 4 (31.3%) were predominant. The MIC90 values of amoxicillin, gentamycin, imipenem, ciprofloxacin, and clarithromycin were 4, 0.5, 0.25, 64, and 128 mg/L, respectively. CONCLUSIONS: Since there is no recommended guideline yet for the choice or duration of antibiotic therapy and antimicrobial break points, our results suggested, for the first time, that prolonged antibiotic therapy, except with ciprofloxacin and clarithromycin, would be required to ensure resolution of symptoms and prevention of recurrence.

Hypervirulent clade 2, ribotype 019/sequence type 67 Clostridioides difficile strain from Japan.

BACKGROUND: Clostridioides difficile ribotype (RT) 019/sequence type (ST) 67 strains belong to a hypervirulent lineage closely related to RT027/ST1; however, limited data are available for hypervirulent clade 2 lineages in Japan. Herein, we report the draft genome of a C. difficile strain B18-123 belonging to clade 2, RT019/ST67 for the first time in Japan. RESULTS: The pathogenicity locus carried by B18-123 (19.6 kb) showed higher homology (97.29% nucleotide identity) with strain R20291 (RT027/ST1) than the reference strain 630 (RT012/ST54), and B18-123 harbored 8-nucleotide substitutions in tcdC. However, it did not contain an 18-base pair (bp) deletion or a single-bp deletion at position 117 in tcdC, which was identified in the previous strain R20291. A cytotoxicity assay revealed similar cytotoxicity levels between strains B18-123 and ATCC BAA-1870 (RT027/ST1). The B18-123 strain was found to be susceptible to metronidazole and vancomycin. CONCLUSION: Our findings contribute to the further understanding of the characteristics of hypervirulent clade 2 including RT019/ST67 lineages.

Whole-genome analysis of EC129, an NDM-5-, CTX-M-14-, OXA-10- and MCR-1-co-producing Escherichia coli ST167 strain isolated from Japan.

OBJECTIVES: The emergence and spread of carbapenemase-producing Enterobacteriaceae is a worldwide concern. This study reports the whole genome sequence of an NDM-5-, CTX-M-14-, OXA-10- and MCR-1-co-producing Escherichia coli sequence type 167 (ST167) multidrug-resistant clinical strain (EC129) isolated from a sputum sample of a hospitalised patient diagnosed with pneumonia. METHODS: The genome of E. coli EC129 was subjected to next-generation sequencing and reads were assembled. The draft genome was annotated using DDBJ Read Annotation Pipeline DFAST server, followed by subsequent in silico analysis. RESULTS: The genome of E. coli ST167 strain EC129 is 5319159 bp in length and contains 5022 protein-coding sequences. The blaNDM-5, blaCTX-M-14, blaOXA-10 and mcr-1 genes were detected along with other antimicrobial resistance genes conferring resistance to aminoglycosides, fluoroquinolones, sulfonamides, trimethoprim and tetracyclines. Antimicrobial susceptibility testing revealed that the isolate was resistant to all antimicrobial agents except colistin. CONCLUSION: To our knowledge, this study is the first to report anE. coli ST167 strain co-producing NDM-5, CTX-M-14, OXA-10 and MCR-1 isolated from a sputum sample of an individual with pneumonia in Japan, thus elucidating the molecular characteristics and resistance gene diversity of this strain.

Prevention of surgical site infection via antibiotic administration according to guidelines after gynecological surgery.

AIM: We modified the antimicrobial prophylaxis of surgical site infection (SSI) according to the guidelines of the Japanese Society of Chemotherapy and Japan Society of Infectious Diseases (hereinafter referred to as optimization) and measured outcomes. METHODS: From April 2016 to March 2017, we performed cesarean section and open hysterectomy with optimization, and compared the outcome to that of surgery performed without optimization between April 2014 and March 2016. We measured the rates of antibiotic discontinuation, appropriate antibiotic selection, SSI incidence, resumption of antibiotic therapy and fever incidence, as well as the length of postoperative hospital stay and medical expenses for antibiotics to evaluate the appropriateness and outcomes of antibiotic prophylaxis. RESULTS: Optimization resulted in a change in the method of selecting antibiotics for cesarean section, but there was no change in SSI incidence rate (0.74% vs 0.0%, P = 0.36). Optimization reduced the use of antibiotics and medical expenses of hysterectomy (median reduction of 50% and 78% for hysterectomy without or with lymphadenectomy, respectively). However, there was no change in outcome regarding SSI incidence (5.7% vs 0.0%, P = 0.11 and 7.8% vs 9.5%, P = 0.77, respectively). CONCLUSION: Appropriate use of antibiotics according to guidelines reduced antibiotic dose and medical expenses, but there was no change in outcome regarding SSI incidence rate. These findings suggested that implementation of dosing regimens according to the guidelines would be useful to reduce antibiotic medicine costs and prevent resistant bacteria and complications associated with antibiotics.

Molecular typing of methicillin-resistant Staphylococcus aureus: Comparison of PCR-based open reading frame typing, multilocus sequence typing, and Staphylococcus protein A gene typing.

The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA.