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

Noriko Takeuchi; Misako Ohkusu; Tadashi Hoshino; Sachiko Naito; Akiko Takaya; Tomoko Yamamoto; Naruhiko Ishiwada

doi:10.1016/j.jiac.2016.12.012

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

J Infect Chemother. 2017 Apr;23(4):218-223. doi: 10.1016/j.jiac.2016.12.012. Epub 2017 Jan 31.

Authors

Noriko Takeuchi¹, Misako Ohkusu², Tadashi Hoshino³, Sachiko Naito⁴, Akiko Takaya⁵, Tomoko Yamamoto², Naruhiko Ishiwada²

Affiliations

¹ Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba, Japan. Electronic address: koinori101@chiba-u.jp.
² Department of Infectious Diseases, Medical Mycology Research Center, Chiba University, Chiba, Japan.
³ Division of Infectious Diseases, Chiba Children's Hospital, Chiba, Japan.
⁴ Department of Pediatrics, Chiba University Hospital, Chiba, Japan.
⁵ Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan.

PMID: 28159338
DOI: 10.1016/j.jiac.2016.12.012

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.

Keywords: Children; Fluoroquinolones; Quinolone-resistant; Streptococcus pneumoniae.

MeSH terms

Anti-Bacterial Agents / therapeutic use*
Child
Child, Preschool
Drug Resistance, Bacterial / genetics*
Female
Fluoroquinolones / therapeutic use*
Genes, Bacterial / genetics
Humans
Japan
Male
Pneumococcal Infections / drug therapy
Pneumococcal Infections / microbiology
Quinolones / therapeutic use*
Streptococcus pneumoniae / drug effects*
Streptococcus pneumoniae / genetics
Streptococcus pneumoniae / isolation & purification*
beta-Lactamases / genetics

Substances

Anti-Bacterial Agents
Fluoroquinolones
Quinolones
beta-Lactamases