Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks.

Background/Objectives: The increasing prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms poses a significant clinical challenge worldwide due to limited oral treatment options. Tebipenem (TBPM), an oral carbapenem antibiotic, is currently approved only for pediatric use in Japan, with no adult indication established. International studies have shown promising results for ESBL-producing infections, but optimal dosing regimens for Japanese adults with varying renal function have not been established. This study aimed to determine the optimal TBPM dosing regimens for ESBL-producing Enterobacterales UTIs in Japanese patients stratified by renal function, providing evidence for potential adult approval applications in Japan. Methods: Monte Carlo simulations (MCSs) were performed using pharmacokinetic parameters derived from clinical trials in Japanese subjects. Various dosing regimens were evaluated across different creatinine clearance (CCR) ranges and minimum inhibitory concentrations (MICs). The pharmacokinetic/pharmacodynamic target was set at fAUC_0–24/MIC·1/tau ≥ 34.58, with a ≥90% probability of target attainment (PTA) considered optimal. Results: For patients with severe renal impairment (CCR < 30 mL/min), 150 mg q12 h achieved a >90% PTA against ESBL-producing organisms with an MIC of 0.03 mg/L. For moderate-to-severe renal impairment (30 ≤ CCR < 50 mL/min) and moderate renal impairment (50 ≤ CCR < 80 mL/min), 300 mg q8 h maintained a >90% PTA. For normal renal function (CCR ≥ 80 mL/min), 600 mg q8 h was required to achieve the target PTA. Conclusions: This first Japanese PK/PD analysis of TBPM in ESBL-producing UTIs provides evidence-based dosing recommendations across various renal function levels. TBPM, with appropriate renal-adjusted dosing, may offer an effective oral treatment option for patients who have traditionally required hospitalization for parenteral therapy.

Background: Hospitals are recognized as point sources of antimicrobials in urban wastewater systems; however, comprehensive evaluations of their discharge profiles have not yet been conducted. Methods: This study presents a multi-site investigation of residual antimicrobial concentrations in effluents from five general hospitals and a commercial facility in the metropolitan area of Japan. Over a 12-week period (December 2023–March 2024), extensive sampling was conducted. Fifteen antimicrobials from multiple classes were quantified using high-throughput analysis. Results: The results revealed consistently higher concentrations in hospital effluents, particularly for levofloxacin, vancomycin, and ampicillin, than in non-clinical sites. Distinct facility-specific and temporal patterns suggest strong links between local prescribing practices and the effluent composition. Some compounds, such as clarithromycin and minocycline, showed dual contributions from both hospital and commercial sources. Conclusions: These findings highlight the need for source-targeted monitoring and antimicrobial pollution control strategies and provide a foundation for expanding surveillance efforts and informing environmental policies related to antimicrobial resistance (AMR).

Background/Objectives: Comparative analysis of antimicrobial resistomes in hospital and community wastewater can provide valuable insights into the diversity and distribution of antimicrobial resistance genes (ARGs), contributing to the advancement of the One Health approach. This study aimed to characterize and compare the resistome profiles of wastewater sources from a hospital and community. Methods: Longitudinal metagenomic analysis was conducted on wastewater samples collected from the National Center for Global Health and Medicine (hospital) and a shopping mall (community) in Tokyo, Japan, between December 2019 and September 2023. ARG abundance was quantified using reads per kilobase per million mapped reads (RPKM) values, and comparative analyses were performed to identify the significantly enriched ARGs in the two sources. Results: A total of 46 monthly wastewater samples from the hospital yielded 825 unique ARGs, with a mean RPKM of 2.5 across all detected genes. In contrast, 333 ARGs were identified in the three shopping mall wastewater samples, with a mean RPKM of 2.1. Among the ARGs significantly enriched in the hospital samples, 23, including genes conferring resistance to aminoglycosides (nine groups) and β-lactam antibiotics (eight groups), exhibited significantly high RPKM values. No ARGs were found to be significantly enriched in the community wastewater samples. Conclusions: This study highlights the higher diversity and abundance of ARGs, particularly those conferring resistance to aminoglycosides and β-lactam antibiotics including carbapenems, in hospital wastewater than in community wastewater. These findings underscore the importance of continuous resistome monitoring of hospital wastewater as part of the integrated One Health surveillance strategy.

Nasopharyngeal swab sampling can be limited by critical factors, such as dependence on medical staff, invasiveness, nosocomial transmission, and occupational exposure risk. This study aimed to investigate whether saliva and nasal vestibular swabs are suitable non-invasive alternatives to nasopharyngeal swabs for influenza A detection in severe acute respiratory infections (SARIs). Saliva samples demonstrated a higher sensitivity (87.5%) than did nasal vestibular swabs (31.3%) in RT-qPCR. While nasal vestibular swabs showed inconsistent results, saliva samples consistently tested positive, particularly within 7 days of symptom onset (100% positive agreement). In addition, diagnosis with RT-qPCR is often delayed because it requires trained laboratory technicians and facilities with appropriate laboratory settings. Therefore, the GenPad®, a rapid diagnostic device, was evaluated and showed promising performance (92.9%) compared with the efficiency of RT-qPCR. Factors such as the location of infection (upper vs. lower respiratory tract infections), sample collection timing, pre-collection instructions, and nucleic acid extraction possibly contributed to the detection efficiency. Despite the small sample size (n=16) and lack of influenza-negative controls, our findings support saliva as a viable self-collected diagnostic sample for influenza A diagnosis and surveillance programs. Non-invasive sampling mitigates discomfort, minimizes infection risk for healthcare workers, and improves testing capacity, particularly under frequent staff shortages during pandemics. Highlights We aimed to propose alternatives to nasopharyngeal swab sampling Saliva samples demonstrated a high sensitivity in RT-qPCR Nasal vestibular swab samples may pose a risk of sampling bias The GenPad® demonstrated performance comparable to that of the RT-qPCR method