JAC Advance Access published online on January 23, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki487
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1 Johnson & Johnson Pharmaceutical Research & Development L.L.C., 1000 Route 202, Raritan, NJ, USA
* To whom correspondence should be addressed. Objectives: Prevalence of single quindone-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 Results: No QRDR mutations were found in any of the isolates with levofloxacin MICs Conclusions: Overall prevalence of single QRDR mutations in levofloxacin-susceptible S. pneumoniae with MICs of
Received September 30, 2005
Revised December 9, 2005
Accepted December 15, 2005
Original article
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)
Todd A. Davies 1 *,
Y. Cheung Yee 2,
Raul Goldschmidt 1,
Karen Bush 1,
Daniel F. Sahm 3,
and
Alan Evangelista 2
2 Ortho-McNeil, Inc., 1000 Route 202, Raritan, NJ, USA
3 Focus Bio-Inova, Inc., 13665 Dulles Technology Drive, Suite 200, Herndon, VA, USA
Todd A. Davies, E-mail: tdavies{at}prdus.jnj.com
Abstract 
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.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).2 mg/L was 0.4% (4/1106) and has remained <1% within nine institutions over 5 years (1999-2003).
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