土井 洋平

BACKGROUND AND OBJECTIVES: Carbapenem-resistant Gram-negative bacilli (CRGNB), especially Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii, are critical pathogens associated with excess morbidity and mortality. To elucidate their molecular epidemiology and clinical outcomes in Japan, patients with CRGNB were enrolled in the MDR organisms clinical research network (MDRnet) consisting of eight tertiary care facilities. METHODS: Between 2019 and 2022, 246 unique patients with carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant P. aeruginosa (CRPA) and carbapenem-resistant A. baumannii (CRAB) isolates were prospectively enrolled. RESULTS: A total of 246 isolates were collected from 246 patients, including 78 (31.7%) CRE, 167 (67.9%) CRPA and 1 (0.4%) CRAB. For CRE, 74.4% of the isolates carried carbapenemase genes with predominance of bla IMP (64.1%). Only 2.4% of CRPA had carbapenemase genes, which was lower than CRE. Among the infected patients, 20.0% and 12.5% died of CRE and CRPA within 30 days, respectively. In patients with CRE, the mortality rate within 30 days for those without carbapenemase-producing Enterobacterales (CPE) was higher compared with those with CPE (22.2% compared with 18.8%). CONCLUSIONS: Our study highlights the unique molecular epidemiology and clinical outcomes of CRGNB in Japan.

BACKGROUND: With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir (RDV), a broad-spectrum antiviral. Given the evolving nature of COVID-19, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review (SLR) with meta-analysis (MA) to summarize RDV effectiveness among hospitalized adults. METHODS: We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining RDV efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model MA was used, with subgroup analyses for randomized controlled trials (RCT) and real-world (RW) studies. RESULTS: From January 2019 to December 2023 over 18,000 sources were screened and 122 unique studies were identified, reporting on 25,174 participants in RCTs and 1,279,859 in RW studies. Remdesivir significantly increased survival in the overall population [OR: 0.69 (0.55-0.86); p=0.001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen [OR: 0.81 (0.75-0.88)], low-flow oxygen [OR: 0.71 (0.64-0.79)], high-flow oxygen [OR: 0.87 (0.83-0.91)] and invasive mechanical ventilation [OR: 0.78 (0.68-0.90)]. Rehospitalization risk was significantly reduced in patients receiving remdesivir [OR: 0.72 (0.64-0.81)]. CONCLUSION: Our comprehensive SLR, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection receiving RDV across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.

We explored the role of commensal Neisseria in the emergence of third-generation cephalosporin-resistant N. meningitidis. Cefotaxime resistance-conferring penA795 was prevalent among commensal Neisseria isolates in Shanghai, China, and was acquired by a serogroup C quinolone-resistant sequence type 4821 N. meningitidis, Nm507, causing fulminant meningitis in an unvaccinated 2-year-old child.

BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) has been increasingly reported worldwide, posing a severe challenge to public health; however, the mechanisms driving its emergence and global dissemination remain unclear. METHODS: We analysed CR-hvKp strains derived from canonical hvKp backgrounds, and acquired a carbapenemase-encoding gene. These strains were identified from 485 CRKp isolates in the CRACKLE-2 China cohort, 259 CRKp isolates from a multi-centre study, and 67,631 K. pneumoniae genomes available in GenBank. Clinical isolates harbouring the IncFIIK34 KPC-2 plasmid were selected for genome sequencing, RNA-Seq, conjugation assays, in vivo, ex vivo, and in vitro phenotypic characterisation. FINDINGS: Analysis of clinical CR-hvKp isolates and the 414 genomes from 24 countries available in GenBank identified an IncFIIK34 KPC-2 plasmid as the prevalent KPC plasmid (detected in 25%, 45/178 of KPC-producing CR-hvKp). Compared with the epidemic IncFIIK2 KPC-2 plasmid, the IncFIIK34 KPC-2 plasmid exhibited a 100- to 1000-fold increase in conjugation frequency (10-4-10-5 vs. 10-7) and an in vitro growth advantage under meropenem challenge-likely due to the overexpression of conjugation-related genes and an increased blaKPC copy number and expression. CR-hvKp isolates and hvKp transconjugants carrying this plasmid often exhibited reduced mucoviscosity, while retaining hypervirulence in both murine models and human neutrophil assays. INTERPRETATION: The IncFIIK34 plasmid may be a key factor driving the global dissemination of CR-hvKp, underscoring the urgent need for enhanced molecular surveillance of this emerging pathogen. FUNDING: National Natural Science Foundation of China and National Institutes of Health.

BACKGROUND: The incidence of syphilis has been rising globally but effective screening strategies are lacking. Preoperative syphilis screening is commonly performed at Japanese hospitals for infection prevention purposes. However, its effectiveness in improving subsequent management is unclear. METHODS: A retrospective cohort study was conducted to assess the effectiveness of universal preoperative syphilis screening testing implemented at a Japanese tertiary care hospital from April 2017 to March 2023. The annual prevalence of positive preoperative treponemal tests was tracked, and subsequent clinical management for patients with a positive test result was investigated. Attributes of patients with a positive result who were more likely to receive further evaluation were also elucidated. RESULTS: In total, 82,439 patients underwent surgery during the study period. Preoperative treponemal testing was performed in 94.8% (78,170/82,439) of the patients. A positive test result was recorded in 544 (0.70%) with an annual positivity rate ranging from 0.61 to 0.83%, whereas the proportion of presumed active syphilis ranged from 0.02 to 0.08%. A total of 85 patients with a positive syphilis screening test, a nontreponemal test with a positive titer, and without history of syphilis were identified. Of those, only 45 patients (52.9%) received further evaluation. CONCLUSION: The positivity of preoperative treponemal testing was low despite the rising incidence of syphilis in Japan, and the prevalence of presumed active syphilis identified during the preoperative period was even smaller. Routine treponemal testing in the preoperative setting had limited utility in effectively identifying patients with active syphilis.