土井 洋平

INTRODUCTION: At the time of this study, no approved treatment for mpox was available in Japan, and data on the clinical course and virological changes during tecovirimat treatment were limited. METHODS: We conducted a prospective multicenter observational case series of patients with PCR-confirmed mpox between June 28, 2022, and March 31, 2025, to describe the clinical course and safety of a 14-day course of tecovirimat. Participants could choose treatment or no treatment. RESULTS: All 31 participants received tecovirimat; 24 completed a single 14-day course, and 2 received multiple courses plus vaccinia immune globulin. The median age was 39 years (range, 21-74), and all were men. Nineteen (61.3%) were people living with HIV, with a median CD4 count of 531 cells/μL (range, 50-830), including three with CD4 counts <200 cells/μL. Severe mpox occurred in 23 participants (74.2%), three of whom (9.7%) had risk factors for severe disease, all due to CD4 < 200 cells/μL. Skin lesions were present in 30 participants. At day 14, skin PCR results were available for 23 participants; 16 (69.6%) were negative. No deaths occurred within 14 or 30 days, although one patient with advanced HIV infection died following prolonged hospitalization. Adverse events occurred in 2 participants and were considered unrelated to treatment. DISCUSSION: This prospective multicenter case series describes the clinical course of mpox and temporal dynamics of skin PCR negativity in patients receiving tecovirimat in real-world practice.

BACKGROUND: Antimicrobial resistance (AMR) poses a major global health threat, with health-care-associated infections contributing substantially to mortality. Attributable disease burden remains poorly quantified by relying on cross-sectional and microbiology data. We aimed to characterise AMR epidemiology and disease burden associated with ventilator-associated pneumonia and bloodstream infection in a network of hospitals in Asia. METHODS: This large-scale, prospective, multinational, multicentre cohort study consecutively enrolled patients of any age with microbiologically-confirmed ventilator-associated pneumonia, hospital-acquired bloodstream infections, or health-care-associated bloodstream infections from 41 selected hospitals capable of standardised prospective data collection in 19 Asian countries and regions. Patients with pathogens typically associated with community-acquired infection or not recognised causes of health-care-associated infection were excluded according to predefined protocol criteria, and patients were followed for 28 days. The primary outcome was 28-day mortality from infection onset. Pathogen profiles, antimicrobial prescriptions, attributable mortality, and health-related quality-of-life outcomes were analysed. FINDINGS: Between Sept 1, 2022, and Feb 28, 2025, 10 111 patients were enrolled, and after exclusions, 9496 patients were included in the final analysis. 9642 infection episodes were analysed, comprising 6597 (68·4%) bloodstream infections and 3045 (31·6%) ventilator-associated pneumonia. Of these infections, 7102 (73·7%) of 9642 infection episodes were associated with AMR bacteria, and Gram-negative bacteria were predominant (7599 [78·8%]). Crude 28-day mortality was 2674 (37·7%) of 7102 AMR infection episodes and 1900 (40·6%) of 4683 multidrug resistance infection episodes, with the highest for carbapenem-resistant Acinetobacter spp (CRA; 51·3%) and carbapenem-resistant Enterobacterales (CRE; 48·4%). AMR-attributable mortality was the highest in ventilator-associated pneumonia (16·9%, 95% CI 13·0-20·9), individuals aged 5-14 years (11·7%, 95% CI 1·6-21·8), individuals aged 15-49 years (11·2%, 95% CI 7·2-15·2), and lower-middle-income countries (10·7%, 95% CI 7·0-14·4). By pathogens, CRA and CRE had the highest attributable mortality (19·4%, 95% CI 14·1-24·7 vs 16·2%, 95% CI 12·8-19·6) and also had the poorest quality-of-life outcomes. Most carbapenem-resistant Gram-negative infections were treated with carbapenems (57·8%) or polymyxins (35·6%). INTERPRETATION: AMR bacterial bloodstream infections and ventilator-associated pneumonia were common and associated with high mortality and reduced quality of life in Asia, particularly in infections due to carbapenem-resistant Acinetobacter spp and CRE, and among children and younger adults. The widespread use of suboptimal antimicrobial regimens highlights the urgent need for equitable access to effective therapies and context-specific evidence to guide antimicrobial stewardship. FUNDING: Wellcome Trust, National University of Singapore, Yong Loo Lin School of Medicine, Duke-NUS Medical School, Nanyang Technological University (Lee Kong Chian School of Medicine), Singapore National Centre for Infectious Diseases, and Singapore Medical Research Council.