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.
Pletz
Mathias W R
MW
Department of International Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd., Atlanta, GA 30322, USA. mpletz@sph.emory.edu
McGee
Lesley
L
Jorgensen
James
J
Beall
Bernard
B
Facklam
Richard R
RR
Whitney
Cynthia G
CG
Klugman
Keith P
KP
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