Emergence of high-level penicillin-resistant Neisseria meningitidis harboring ROB-1-type β-lactamase gene in Japan

Abstract

While antimicrobial resistance in Neisseria meningitidis, the causative agent for invasive meningococcal disease (IMD), is rare, some meningococcal isolates in Japan were resistant to ciprofloxacin and penicillin (PCG). Among 290 meningococci isolated from 2003 to 2020 in Japan, four PCG resistant (PCG^R) meningococci were found but showed the minimum inhibitory concentration (MIC) with 0.5 μg/mL at a maximum due to mutation in penA gene that encodes penicillin-binding protein 2. However, we herein report that PCG^R meningococci harboring the ROB-1-type β-lactamase gene (bla_ROB-1) with PCG MIC of 32 μg/mL were isolated in Japan from 2 independent IMD patients at Tokyo in June, and at Shiga in December in 2024. The both isolates were also resistant to another β-lactams, ampicillin and amoxicillin. The PCG^R meningococci with bla_ROB-1, which was genetically classified in sequence type (ST)-3587, was firstly identified in France in 2018 and isolated only in European and American countries until 2024. Phylogenetic analysis with whole genome sequencing revealed that the two Japanese N. meningitidis isolates were not genetically identical and that they were not identical to other ST-3057 meningococci isolated in western countries. The emergence of the bla_ROB-1 positive meningococci in Japan would warn medical risk that β-lactams such as PCG and amoxicillin are not always applicable to IMD treatment and prevention in Japan.