Rybak MJ, Hershberger E, Thomas AM, Seo SM, Kaatz GW; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1999 Sep 26-29; 39: 256 (abstract no. 377).
The Anti-Infective Res. Lab, Detroit Receiving Hosp., Coll. of Pharmacy, Wayne State Univ., Detroit, MI
Although the incidence of VISA remains low, evaluation of newer agents is critical. Newer FQs have improved activity against gram-positive organisms. We evaluated the susceptibilties and killing activity of clinafloxacin (CL), gatifloxacin (G), and trovafloxacin (T), compared to those of levofloxacin (L) cirpofloxacin (C) and sparfloxacin (S) against VISA, VICNS and MRSA. MICs were determined by microdilution. Killing curves were performed at 2x MIC for all FQs where MICs were achievable. The quinolone-resistant-determining-region (QRDR) of 3 VISA and 16 MRSA isolates were examined for grlA and gyrA mutations using PCR and restriction-fragment length polymorphism.RESULTS: MIC (mcg/ml) median, range [table: see text]. All evaluated organisms possessed mutations leading to the most commonly occurring GrlA and GyrA amino acid substitutions that correlated with FQ resistance (codons 79/80 and 83/84), respectively). Less commonly occurring mutations of grlA were not found (codons 84 and 115/116). CL, T and G had lower MICs vs. L, C and S. CL and T had activity against VISA and all FQ except C and S had bactericidal activity against MRSA. It is likely that most isolates of MRSA (including VISA) that are resistant to early FQ such as C have QRDR mutations in both topoisomerases. Such mutations affect the activity of newer FQ to a lesser extent, suggesting that these drugs may be useful in the treatment of infections caused by such organisms.
Publication Types:
Keywords:
- Fluoroquinolones
- Microbial Sensitivity Tests
- Mutation
- Naphthyridines
- Ofloxacin
- Staphylococcal Infections
- Staphylococcal Skin Infections
- Staphylococcus
- Staphylococcus aureus
- Vancomycin
- clinafloxacin
- gatifloxacin
- genetics
- sparfloxacin
- trovafloxacin
Other ID:
UI: 102245336
From Meeting Abstracts