Relative potential for selection of quinolone-resistance-determining-region mutations in Streptococcus pneumoniae by gemifloxacin, gatifloxacin and moxifloxacin
| Autor: | J. Downar, Don E. Low, J.C.S. De Azavedo, Laurie Kilburn, Darrin J. Bast, S. Lad, B. Kong, C.L. Duncan |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
DNA Topoisomerase IV
Topoisomerase IV Gemifloxacin Moxifloxacin Microbial Sensitivity Tests medicine.disease_cause DNA gyrase Gatifloxacin Microbiology Streptococcus pneumoniae Drug Resistance Bacterial medicine Humans Topoisomerase II Inhibitors heterocyclic compounds Pharmacology (medical) Naphthyridines Selection Genetic Cells Cultured Antibacterial agent Pharmacology Aza Compounds biology biochemical phenomena metabolism and nutrition bacterial infections and mycoses Streptococcaceae biology.organism_classification Virology Anti-Bacterial Agents Infectious Diseases Oncology Amino Acid Substitution DNA Gyrase Mutation biology.protein Quinolines medicine.drug Fluoroquinolones |
| Zdroj: | Journal of chemotherapy (Florence, Italy). 18(4) |
| ISSN: | 1120-009X |
| Popis: | Serial passage of a clinical isolate of Streptococcus pneumoniae, in the presence of moxifloxacin, gatifloxacin or gemifloxacin, gave rise to resistant isolates. Non-susceptibility as defined by Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS) breakpoints arose on Days 10, 11, and 12 with gatifloxacin, gemifloxacin, and moxifloxacin respectively. Moxifloxacin and gatifloxacin selected for a single step quinolone-resistant-determining-region (QRDR) mutation in DNA gyrase (GyrA) on Day 4 and 7 respectively, whereas gemifloxacin selected simultaneously for multi-step mutations in gyrase and topoisomerase IV (ParC) on Day 17 and activated a non-reserpine inhibited efflux mechanism by Day 4. As found in clinical isolates, mutations included Ser-81-Phe and Glu-85-Lys in GyrA and Ser-79-Phe or Asp-83-Tyr in ParC. At high MICs, moxifloxacin showed a previously unreported 4 amino-acid deletion in GyrB as well as a more unusual substitution Ser-79-Leu/Ile in ParC. Gemifloxacin showed a 2- to 16-fold greater activity than moxifloxacin or gatifloxacin against strains with two or more QRDR mutations, however, its potency did not translate to nonsusceptibility and gemifloxacin MIC values were either at or well above the CLSI nonsusceptible breakpoint concentration. |
| Databáze: | OpenAIRE |
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