Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: Evidence for clonal spread and the impact of conjugate pneumococcal vaccine

Mathias W.R. Pletz, Lesley McGee, James Jorgensen, Bernard Beall, Richard R. Facklam, Cynthia G. Whitney, Keith P. Klugman

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, ≥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 Spain23F-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.

Original languageEnglish (US)
Pages (from-to)3491-3497
Number of pages7
JournalAntimicrobial agents and chemotherapy
Issue number9
StatePublished - Sep 2004

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases
  • Pharmacology


Dive into the research topics of 'Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: Evidence for clonal spread and the impact of conjugate pneumococcal vaccine'. Together they form a unique fingerprint.

Cite this