Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine.
The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.
Department of International Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, USA. mpletz@sph.emory.edu
Mathias W R
MW
Pletz
Lesley
L
McGee
James
J
Jorgensen
Bernard
B
Beall
Richard R
RR
Facklam
Cynthia G
CG
Whitney
Keith P
KP
Klugman
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation / Q000235:genetics; D015242:Ofloxacin / Q000378:metabolism / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000627:therapeutic use*; D011159:Population Surveillance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014481:United States / Q000453:epidemiology; D018074:Vaccines, Conjugate
D000900:Anti-Bacterial Agents; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D064704:Levofloxacin; D015242:Ofloxacin