JAC Advance Access originally published online on January 23, 2006
Journal of Antimicrobial Chemotherapy 2006 57(3):437-442; doi:10.1093/jac/dki487
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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)
1 Johnson & Johnson Pharmaceutical Research & Development L.L.C., 1000 Route 202, Raritan, NJ, USA; 2 Ortho-McNeil, Inc., 1000 Route 202, Raritan, NJ, USA; 3 Focus Bio-Inova, Inc., 13665 Dulles Technology Drive, Suite 200, Herndon, VA, USA
Received 30 September 2005; returned 7 November 2005; revised 9 December 2005; accepted 15 December 2005
* Correspondence address. Tel: +1-908-707-3465; Fax: +1-908-707-3501; Email: tdavies{at}prdus.jnj.com
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
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