Emergence of quinolone-resistant strains in Streptococcus pneumoniae isolated from paediatric patients since the approval of oral fluoroquinolones in Japan

Abstract Tosufloxacin (TFLX) is a fluoroquinolone antimicrobial agent. TFLX granules for children were initially released in Japan in 2010 to treat otitis media and pneumonia caused by drug-resistant bacteria, e.g. penicillin-resistant Streptococcus pneumoniae and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae . The evolution of bacterial resistance since TFLX approval is not known. To clarify the influence of quinolones administered to children since their approval, we examined the resistance mechanism of TFLX-resistant S. pneumoniae isolated from paediatric patients as well as patient clinical characteristics. TFLX-resistant strains (MIC ≥ 2 mg/L) were detected among clinical isolates of S. pneumoniae derived from children (≤15 years old) between 2010 and 2014. These strains were characterised based on quinolone resistance-determining regions (QRDRs), i.e. gyrA , gyrB , parC , and parE. In addition, the antimicrobial susceptibility, serotype, and multilocus sequence type of strains were determined, pulsed-field gel electrophoresis was performed, and patient clinical characteristics based on medical records were assessed for cases with underling TFLX-resistant strains. Among 1168 S. pneumoniae isolates, two TFLX-resistant strains were detected from respiratory specimens obtained from paediatric patients with frequent exposure to TFLX. Both strains had mutations in the QRDRs of gyrA and parC . One case exhibited gradual changes in the QRDR during the clinical course. This is the first study of quinolone-resistant S. pneumoniae isolated from children, including clinical data, in Japan. These data may help prevent increases in infections of quinolone-resistant S. pneumoniae in children; specifically, the results emphasise the importance of administering fluoroquinolones only in appropriate cases.