Publications
| Garenoxacin (Gar) Exhibits Potent Activity Against Genetically Constructed Resistant Strains Of Streptococcus pneumoniae (Sp). |
Authors: J.S. DeAzavedo, M. Aquino, C.L. Duncan, M. Yue, D.E. Low, D.J. Bast.
Background: Gar (BMS-284756) is a novel des-F(6)-quinolone that has shown exceptional potency against several clinically important gram-positive organisms, including both susceptible & nonsusceptible Sp. In this study, we evaluated the activity of Gar & comparator quinolones against 13 Sp isolates with defined single & multiple amino acid substitutions in the ParC & GyrA subunits of topoisomerase IV & DNA gyrase, respectively.
Method: Isogenic mutants of the fluoroquinolone-susceptible Sp R6 strain were generated by genetic transformation (Table). The most commonly selected amino acid substitutions for S79 & D83 in the ParC subunit & S81 & E85 in the GyrA subunit were studied (S, serine; F, phenylalanine; D, aspartic acid; Y, tyrosine; E, glutamic acid; K, lysine). MICs were determined using the NCCLS recommended broth microdilution assay (Lev, levofloxacin; Gat, gatifloxacin; Mox, moxifloxacin).
Results: Eleven of the 14 (79%) isolates had Gar MICs of < 0.5µg/ml. Gar showed a 2 to 128-fold higher activity than any of the FQs tested for all but one of the strains.
Conclusions: Gar was significantly more active than Lev, Gat & Mox against Sp isolates of varying degrees of FQ susceptibilities, including isolates with double ParC & double GyrA mutations.
Presented At:
42nd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, California, 9/27/2002.
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1999 Microbiology Department, Mount Sinai Hospital, Toronto, ON, Canada.
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