Emergence of ciprofloxacin- and penicillin-resistant Neisseria meningitidis isolates in Japan between 2003 and 2020 and its genetic features

Although we previously reported that some meningococcal isolates in Japan were resistant to penicillin (PCG) and ciprofloxacin (CIP), the antibiotic susceptibilities of Neisseria meningitidis isolates obtained in Japan remained unclear. In the present study, 290 N. meningitidis isolates in Japan between 2003 and 2020 were examined for the sensitivities to eight antibiotics (azithromycin, ceftriaxone, ciprofloxacin, chloramphenicol, meropenem, minocycline, penicillin, and rifampicin). All isolates were susceptible to chloramphenicol, ceftriaxone, meropenem, minocycline, and rifampicin while two were resistant to azithromycin. Penicillin- and ciprofloxacin-resistant and -intermediate isolates (PCG (R), CIP (R), PCG(I) and CIPI, respectively) were also identified. Based on our previous findings from whole genome sequence analysis, approximately 40% of PCG(I) were associated with ST-11026 and cc2057 meningococci, both of which were unique to Japan. Moreover, the majority of ST-11026 meningococci were CIP (R) or CIPI. Sensitivities to PCG and CIP were closely associated with genetic features, which indicated that, at least for Japanese meningococcal isolates, PCG(R/I) or CIPI/R would be less likely to be horizontally conferred from other neisserial genomes by transferring of the genes responsible (penA and gyrA genes, respectively), but rather that ancestral N. meningitidis strains conferring PCG(R/I) or CIPI/R phenotypes clonally disseminated in Japan.