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Objectives Some MRSA strains produce Panton–Valentine leucocidin (PVL) and/or toxic shock syndrome toxin 1 (TSST-1), which are associated with severe infectious diseases. Although PVL- or TSST-1-positive strains have been isolated worldwide, strains carrying both PVL and TSST-1 genes are rare and sporadic. The objective of this study was to characterize these strains from Japan. Methods A total of 6433 MRSA strains isolated in Japan between 2015 and 2021 were analysed. Molecular epidemiological and comparative genomic analyses were conducted on PVL- and TSST-1-positive MRSA strains. Results A total of 26 strains from 12 healthcare facilities were PVL positive and TSST-1 positive, and all were classified as clonal complex (CC) 22. These strains exhibited similar genetic features to each other and were named as ST22-PT according to a previous report. Twelve and one of the ST22-PT strains were identified in patients with deep-seated skin infections and toxic shock syndrome-like symptoms, which are typical clinical features of PVL-positive and TSST-1-positive Staphylococcus aureus, respectively. Whole-genome comparative analysis revealed that the ST22-PT strains were highly similar to PVL- and TSST-1-positive CC22 strains isolated in several countries. Evaluation of the genome structure showed that ST22-PT possessed ΦSa2 harbouring PVL genes and a unique S. aureus pathogenicity island harbouring the TSST-1 gene. Conclusions ST22-PT strains have recently emerged from several healthcare facilities in Japan, and ST22-PT-like strains have been identified in several countries. Our report highlights that the risk of international spread of PVL- and TSST-1-positive MRSA clone ST22-PT needs to be further investigated.

Fig. S1. Number of third-generation cephalosporin-susceptible and resistant pneumococcal meningitis cases. Susceptible: third-generation cephalosporin-susceptible; resistant: third-generation cephalosporin-resistant; PCV7 was introduced in 2010, and PCV13 was introduced 2013. The patients have been decreasing since introduction of vaccination.Table S1. Characteristics of patients infected with third-generation cephalosporin-susceptible and third-generation cephalosporin-resistant pneumococcal isolates.

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The objective of this study was to describe clinical features and to assess the risk factors associated with mortality in Pseudomonas aeruginosa bacteraemia in a tertiary Japanese paediatric care hospital. Methods: Patients diagnosed with P. aeruginosa bacteraemia at our hospital between 2007 and 2018 were analysed in a retrospective case series. Inadequate initial therapy for P. aeruginosa bacteraemia was defined as initial treatment without antipseudomonal antibiotics or an administration of antipseudomonal agent to which the causative strain was resistant. Bacteraemia-related death was defined as all deaths occurring within 7 days after the onset of bacteraemia. Results: Overall, 41 patients with 42 P. aeruginosa bacteraemia episodes were identified. The most common underlying condition was malignancy (27%), followed by congenital heart disease (20%) and preterm birth (17%). Among the 42 P. aeruginosa clinical isolates, 24% were resistant to at least one of the antipseudomonal agents and 10% were resistant to more than one agent. The susceptibility levels for piperacillin, fourthgeneration cephalosporins and ciprofloxacin were higher than that for carbapenems. Bacteraemia-related death was observed in 43% of episodes. The 30-day all-cause mortality was 50% (standard error 8%). Neonates, intensive care, mechanical ventilation, afebrile episodes, septic shock, hypoxia, renal injury and inadequate initial therapy were associated with bacteraemia-related death episodes. Conclusions: We found that childhood P. aeruginosa bacteraemia is still a high mortality disease. Our results imply the importance of the identification of high-risk patients and the establishment of adequate empirical antibiotic therapy.