Molecular Analysis of Levofloxacin-resistant Streptococcus pneumoniae in Japan

抄録

Quinolone resistance has been attributed to amino acid mutations in the type II topoisomerases of pathogens. To better understand this mechanism of resistance, we analyzed the molecular epidemiology of levofloxacin-resistant Streptococcus pneumoniae in Japan. We measured the quinolone susceptibility of 668 strains of S. pneumoniae obtained through nationwide surveillance from 2006 to 2008. We also sequenced the quinolone resistance-determining regions (QRDRs) in type II topoisomerases and analyzed the relationship between minimum inhibitory concentration (MIC) and six specific mutations (Ser81 or Glu85 in GyrA, Asp435 in GyrB, Ser79 or Asp83 in ParC, and Asp435 in ParE). Eighteen of the isolated strains (2.7%) showed intermediate susceptibility and resistance to levofloxacin (MIC > 4µg/ml), with no significant difference among years. However, garenoxacin and sitafloxacin showed excellent activity against these strains. Of the 18 strains, 17 (94.4%) showed mutation in QRDRs, while in 12 out of 14 levofloxacin-resistant strains (85.7%) two or more mutations were identified. A single QRDR mutation was found in 3 of 60 levofloxacin-susceptible strains (5%), all of which had an MIC of 2µg/ml. We therefore found a high isolation frequency of levofloxacin-resistant S. pneumonia in Japan over a 2-year period. Furthermore, QRDR mutations were present in 5% of susceptible strains; these were thought to be in the early stages of resistance. In the future, the increasing use of levofloxacin might result in more strain resistance. We therefore suggest that strong quinolones such as garenoxacin and sitafloxacin could be proactively administered to high-risk patients.