Journal Article

Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase genes among US levofloxacin-susceptible clinical isolates of <i>Streptococcus pneumoniae</i> from nine institutions (1999–2003)

Todd A. Davies, Y. Cheung Yee, Raul Goldschmidt, Karen Bush, Daniel F. Sahm and Alan Evangelista

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 57, issue 3, pages 437-442
Published in print March 2006 | ISSN: 0305-7453
Published online January 2006 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki487
Infrequent occurrence of single mutations in topoisomerase IV and DNA gyrase genes among US levofloxacin-susceptible clinical isolates of Streptococcus pneumoniae from nine institutions (1999–2003)

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Objectives: Prevalence of single quinolone-resistance determining region (QRDR) mutations in Streptococcus pneumoniae was studied from nine institutions over 5 years to track the incidence of single QRDR mutations.

Methods: All 1106 levofloxacin-susceptible pneumococci (MICs ≤2.0 mg/L) identified from 1112 total isolates (99.5% susceptibility) in TRUST 3 (1999), TRUST 5 (2001) and TRUST 7 (2003) surveillance studies from the same nine hospitals in nine states were screened for QRDR mutations. Using pyrosequencing, the strains were screened for mutations corresponding to hot spots Asp-78, Ser-79 and Asp-83 in ParC; Asp-80, Ser-81 and Glu-85 in GyrA; Asp-435 in ParE and Asp-435 in GyrB. DNA sequencing of QRDRs was performed to confirm mutations.

Results: No QRDR mutations were found in any of the isolates with levofloxacin MICs ≤0.5 mg/L and no gyrA or gyrB QRDR mutations were found in any of the screened isolates (MICs ≤2 mg/L). Four single-step QRDR mutants with the following amino acid substitutions were found: ParE Asp-435 to Asn (isolated in 1999 in Colorado); ParC Asp-83 to Asn (isolated in 2001 in Kentucky); ParC Ser-79 to Phe (isolated in 2003 in Indiana) and ParC Ser-79 to Tyr (isolated in 2003 in California). These non-clonal strains had levofloxacin MICs of 1 mg/L and were non-susceptible to ciprofloxacin (MIC 2–4 mg/L).

Conclusions: Overall prevalence of single QRDR mutations in levofloxacin-susceptible S. pneumoniae with MICs of ≤2 mg/L was 0.4% (4/1106) and has remained <1% within nine institutions over 5 years (1999–2003).

Keywords: fluoroquinolones; QRDRs; parC

Journal Article.  4025 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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