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  • Title: In vitro activity of sitafloxacin against clinical strains of Streptococcus pneumoniae with defined amino acid substitutions in QRDRs of gyrase A and topoisomerase IV.
    Author: Touyama M, Higa F, Nakasone C, Shinzato T, Akamine M, Haranaga S, Tateyama M, Nakasone I, Yamane N, Fujita J.
    Journal: J Antimicrob Chemother; 2006 Dec; 58(6):1279-82. PubMed ID: 17056610.
    Abstract:
    OBJECTIVES: Fluoroquinolone-resistant Streptococcus pneumoniae are increasing worldwide rapidly. In vitro activities of sitafloxacin were evaluated against clinical isolates of S. pneumoniae resistant to levofloxacin (MIC of levofloxacin > or = 4 mg/L), which were characterized genetically. METHODS: The quinolone resistance determining regions (QRDRs) of gyrA, gyrB, parC and parE of these strains were analysed by PCR-based sequencing. MICs of sitafloxacin and other quinolones were determined by a microdilution broth method. RESULTS: All 18 strains had at least one amino acid substitution in the QRDRs of GyrA and ParC, which included Ser-81-->Tyr/Phe and Glu-85-->Lys in GyrA and Ser-79-->Phe/Ile/Tyr, Asp-83-->Tyr, Asn-91-->Asp, Ser-107-->Phe, Lys-137-->Asn and Ala-142-->Ser in ParC. Most isolates had Asp-435-->Asn/Ile-460-->Val/Ala-596-->Thr substitutions in ParE, while no amino acid substitution in GyrB was noted in all isolates. Ten isolates for which levofloxacin MICs were 16 or 32 mg/L had multiple mutations in both GyrA and ParC. The MIC80 value of sitafloxacin for levofloxacin-resistant isolates was 0.25 mg/L. The range of MICs of sitafloxacin for isolates resistant to levofloxacin (MIC 4-32 mg/L) was 0.016-0.5 mg/L. CONCLUSIONS: These findings warrant further studies to evaluate the usefulness of sitafloxacin in the treatment of levofloxacin-resistant S. pneumoniae infection.
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