Yoshiaki Gu

Objective: To assess the impact of a pharmacist-led anti-methicillin-resistant Staphylococcus aureus (MRSA) agents’ time-out and identify clinical areas most likely to benefit. Design: Single-center before–after interrupted time-series study. Setting: An 813-bed tertiary hospital in Tokyo, Japan. Patients: Inpatients receiving intravenous anti-MRSA agents. Methods: Stewardship pharmacists alerted physicians to reassess intravenous anti-MRSA therapy at 72 hours after its start. Monthly days of therapy per 1,000 patient-days (DOT) were compared between October 2017 to September 2022 and October 2022 to September 2024 after stratification by ward and department. Acceptance rate and therapeutic drug monitoring (TDM) tests were also assessed. Results: Hospital-wide DOT showed an immediate non-significant decrease (−19.23; 95% confidence interval [CI] −59.17 to 20.72; P = .35) and no significant trend change (+0.82; 95% CI −1.18 to 2.82; P = .42). In emergency medicine, DOT decreased in critical care (slope change −20.3; 95% CI −36.25 to −4.28; P = .01) and general wards (−31.6; 95% CI −61.4 to −1.79; P = .04). In emergency medicine critical care, vancomycin use decreased (level change −406.1; 95% CI −801.3 to −10.9; P = .04) with a reduced trend (slope change −24.5; 95% CI −41.2 to −7.8; P < .001). Acceptance was higher in critical care than in general wards (77.1% [27/35] vs 33.6% [40/119]). TDM tests per 1,000 patient-days decreased (8.47 ± 2.39 to 6.55 ± 1.18; P < .001), with no increase in length of stay or in-hospital mortality. Conclusions: Targeting an implementation to areas most likely to benefit from it may improve antimicrobial stewardship when resources are limited. Complementary strategies may be needed if acceptance is poor.

Background: Inappropriate antibiotic allergy labeling often leads to the unnecessary avoidance of first-line therapies. The present study aimed to evaluate the current status of antibiotic allergy documentation and its assessment in patients undergoing surgery for which cefazolin was the recommended first-line prophylaxis in a Japanese hospital. Methods: This retrospective observational study was conducted at a university hospital in Tokyo from 2021 to 2023; included patients with a history of antimicrobial allergy who underwent surgery for which cefazolin was recommended; and assessed patient demographics, details of the allergies in electronic health records (EHR), and perioperatively administered antimicrobial agents. Results: Of 2,402 eligible patients, 243 (10.1%) had a registered antimicrobial allergy. The drug classes most frequently recorded in the EHR were cephalosporins (25.0%) and penicillins (24.0%). Documentation of allergy assessments by a physician (9.0%) or specialist (7.0%) was rare. Although 51.9% of the labeled patients had received cefazolin, non-first-line agents had also been frequently administered. Notably, clindamycin had been administered to 30% of the cases and had been widely used even among patients with only a penicillin allergy label despite the low risk of cross-reactivity. Conclusions: Antibiotic allergy labels in the EHR were often incomplete, infrequently assessed, and associated with substantial avoidance of first-line prophylaxis. Redesigning the EHR format to allow allergies to be distinguished from adverse events while retaining the standard evaluation pathways is essential to optimizing perioperative antimicrobial stewardship.

Objectives: To evaluate an outpatient, antimicrobial stewardship intervention targeting broad-spectrum antimicrobials including third-generation cephalosporins, fluoroquinolones, and macrolides, during an antimicrobial shortage at a Japanese, tertiary hospital. Methods: This before-and-after interventional study was conducted at a tertiary hospital. The intervention included department-focused and hospital-wide education, local guidelines, weekly post-prescription review and feedback, monthly reports on days of therapy (DOT), a formulary review, and an orientation for newly transferred physicians. Counterfactual monthly outcomes (primary endpoint: DOT per 100 visits (DOT/100V) and number of prescriptions per 1000 visits (Rx/1000V) for the target antimicrobials) were predicted on the basis of pre-intervention data using ordinary least squares regression incorporating oral antimicrobial shortages. Results: The post-intervention use of third-generation cephalosporins decreased (DOT/100 V mean difference [MD]: −0.87; 95% confidence interval [CI]: −0.97 to −0.76; Rx/1000 V MD: −3.85; 95% CI: −4.06 to −3.65) together with that of fluoroquinolones (DOT/100V: −1.92; 95% CI: −2.33 to −1.51; Rx/1000V MD: −2.14; 95% CI: −2.60 to −1.68). The volume and frequency of macrolide use did not differ significantly, but inappropriate prescriptions of fluoroquinolones (−26.22%) and macrolides (−7.92%) decreased. Conclusions: This outpatient stewardship programme evaluated within a counterfactual framework accounted for supply shortages, reduced third-generation cephalosporins and fluoroquinolone use, and improved the appropriateness of prescriptions. Sustaining these gains requires on-going evidence-based data-sharing and prescriber-tailored interventions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019 and caused the coronavirus disease 2019 pandemic, has undergone genomic evolution, yielding variants of concern which include the Alpha, Delta, and Omicron variants. Since the virus continues to mutate, we designed this study to assess the impact of SARS-CoV-2 mutations on severity; using PLINK2 software, we analyzed genomic and clinical data from 310 hospitalized patients at the Institute of Science Tokyo Hospital. The analysis identified 64 statistically significant severity-associated mutations. Although the Omicron variants are generally associated with less severe symptoms than the Delta variants, our approach identified statistically significant Omicron variant–specific mutations that were associated with severe disease, as well as additional mutations for which the odds ratios and 95% CIs indicated a consistent trend. Our retrospective analysis of SARS-CoV-2 genomic and clinical information may help clarify the biological significance of mutations.

An analysis of 630 hospitals and 488 COVID-19 clusters in Tokyo (2020/07-2022/05) found contrasting associations between hospital size and cluster frequency. Compared to larger hospitals (≥600 beds), smaller ones (20-99 beds) reported fewer clusters per facility (0.5 vs 2.0), but a higher cluster number per 1000 beds (6.0 vs 2.5).

As COVID‐19 spread worldwide, numerous outbreaks occurred in wards. This study, in addition to investigating the indoor air environment and ventilation characteristics of a ward that had experienced multiple outbreaks, quantitatively evaluated how ventilation characteristics and door operation affect infection risk. Supply and exhaust airflow rates were measured, and ventilation characteristics—including air changes per hour (ACH) in each patient room, the supply–exhaust airflow balance, and ward ventilation pathways—were investigated. Furthermore, assuming the presence of a single index case, computational fluid dynamics (CFD) simulations were performed for four cases combining two airflow conditions and two door‐operation conditions, and the probability of infection under 24 h of exposure was calculated. The results confirmed a substantial ward‐wide decrease in supply airflow, indicating that outdoor air was not sufficiently supplied to patient rooms, and CO ₂ concentrations exceeded 1,000 ppm at some measurement points. While poor ventilation facilitated the dispersion of infectious respiratory particles (IRPs) and increased infection risk, closing doors suppressed IRP dispersion and markedly reduced infection risk. Therefore, checking equipment conditions during normal operation and performing maintenance as needed, together with door operation according to the risk of nosocomial infection, are recommended for infection control in wards.

Antimicrobial resistance (AMR) is a critical global health issue, with inconsistent adherence to antimicrobial stewardship contributing to its worsening. This study aims to assess physicians’ awareness and attitudes towards AMR and appropriate antimicrobial use across different medical specialties in Japan. An online cross-sectional survey was conducted from January 31 to February 5, 2024, among 280 physicians from three specialties (internal medicine, pediatrics, and otorhinolaryngology) who were working in outpatient clinics in Japan. Participants were asked about their familiarity with the National Action Plan (NAP) on AMR and the manuals of Ministry of Health and Labor Welfare (MHLW) on prudent antimicrobial use. Their opinions on AMR facts and antibiotic use were also surveyed using five-point Likert scales. Data were analyzed using descriptive statistics, multilevel mixed-effects ordered logistic regression and generalized linear models to examine factors influencing NAP/manuals adherence. Most respondents were male (85%) and predominantly aged 50 and above (73.9%), Familiarity with the AMR Action Plan varied, with 36.4% of respondents reported understanding its content, while 37.5% only knew its name. Similarly, 27.1% of respondents used the MHLW manuals, whereas 48.6% were aware of them but did not use them. Internal medicine physicians showed the highest adherence to antimicrobial stewardship and most concern about AMR facts, while pediatricians demonstrated the highest adherence to MHLW manuals (AOR = 2.4, p = 0.000 compared to internal medicine doctors). Otorhinolaryngologists reported higher awareness of NAP (AOR = 2.6, p = 0.006 compared to internal medicine doctors) but had the lowest adherence to NAP and MHLW manuals. Younger physicians (< 50 years) were more proactive in addressing AMR and adhering to antimicrobial stewardship than older physicians. Messages emphasizing the prevention of drug resistance and societal impacts of AMR were most associated with positive attitudes from physicians in outpatient clinics. This study highlights significant variability in AMR awareness and adherence across specialties and age groups. Internal medicine physicians showed the highest adherence, while pediatricians were the most familiar with AMR manuals. Otorhinolaryngologists demonstrated strong awareness but lower adherence. Targeted educational interventions, particularly focusing on older physicians and specific specialties, are needed to improve antimicrobial use and combat the growing threat of resistance.

Antimicrobial resistance (AMR) has reached a critical situation globally, prompting urgent national responses to this escalating crisis, including the prioritization of novel antibiotic research. In 2016, Japan initiated a national AMR action plan that promoted appropriate antibiotic use in the country and encouraged a national environment conducive to mitigation measures. However, tackling AMR remains difficult. From an epidemiological perspective, this challenge now extends beyond severe infections, impacting common community-acquired infections, including uncomplicated urinary tract infections (uUTls) and gonorrhea. In uUTIs, the rising prevalence of extended-spectrum β-lactamase-producing and fluoroquinolone-resistant Escherichia coli diminishes the effectiveness of current, routinely used oral antibiotics, necessitating an exploration into innovative solutions. Similarly, the growing resistance of Neisseria gonorrhoeae to antibiotics such as azithromycin raises concerns about the efficacy of current therapeutic options for gonorrhea, which is a highly prevalent sexually transmitted infection. In Japan, since the removal of azithromycin as the recommended first-line treatment, there are no oral first-line antibiotics available to treat gonorrhea. Therefore, novel oral antibiotics are urgently needed for both serious and commonly occurring community-acquired infections. This narrative review discusses the limited availability of novel antibiotics in Japan, the distinctive features of the Japanese antibiotic repertoire and AMR epidemiology, and potential alternative oral treatments for community-acquired infections, including uUTIs and gonorrhea. Japan has been making significant advances toward tackling the AMR crisis through an updated national action plan, AMR policy changes, and innovative approaches to developing novel antibiotics. Substantial international cooperation and the engagement of diverse industry sectors are essential to address the pressing issue of AMR.