RYBAK MJ, CHEUNG C, BROWN WJ; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. A-1150.

Wayne State University, Detroit, MI.

BACKGROUND: Increasing multi-drug resistant Gram-positive bacteria requires the need to evaluate new compounds and their combination for potential treatment regimens. CB-181963, a novel cephalosporin with MRSA activity, Daptomycin (DP) a new lipopeptide, Tigecycline (TG), a new glycylcycline antibiotic, Arbekacin (AB), an aminoglycoside, and Quinupristin/Dalfopristin (QD) and Linezolid (LZ) were evaluated alone and in combination with a variety of antibiotics for potential additivity or synergy against MRSA (n=2), GISA (n=1), VRSA (n=1) and VRE (n=4). METHODS: MICs were determined by microdilution according to NCCLS guidelines. Killing curve experiments were conducted in triplicate (n=324) over 24 hours to evaluate antibiotics alone or in combination at 1/2 the MIC of each antibiotic. Synergy, additivity and indifference were defined as >/= 2 log and 1-2 log, or 0-1 log, respectively, CFU/ml decrease in organisms density compared to the most active agent used alone. RESULTS: MICs are as follows for CB, DP, TG, AB, QD, LZ: MRSA; 2.0, 0.25, 0.25, 0.5, 0.125, 1.0, GISA; 2.0, 0.25, 0.25, 1.0, 0.25, 0.125, VRSA; 4.0, 0.25, 0.25, 0.5, 0.125, 0.25, VREF(faecium); ND (not done), 0.5, 0.125, 32, 1,2, VREF(faecalis); ND, 0.5, 0.125, 32, 16, 2, respectively. In killing curve experiments, the combination of CB+Gent or AB resulted in synergy (4/5 strains) or additivity (1/5) for MRSA, GISA and VRSA. The combination of CB+DP was synergistic against MRSA. The combinations of DP+LZ, DP+DOX, DP+QD and TG+QD resulted in additivity against VREF. CONCLUSIONS: CB plus an aminoglycoside was the most potent combination against S. aureus including multi-drug resistant strains. A number of combinations of antibiotics proved used for additive effects against VRE. These combinations warrant further investigation.

Publication Types:

• Meeting Abstracts

Keywords:

• Acetamides
• Aminoglycosides
• Anti-Bacterial Agents
• CB 181963
• Cephalosporins
• Daptomycin
• Dibekacin
• Doxycycline
• Enterococcus
• Gentamicins
• In Vitro
• Microbial Sensitivity Tests
• Minocycline
• Oxazolidinones
• Rifampin
• Staphylococcal Infections
• Staphylococcus aureus
• Virginiamycin
• dalfopristin
• habekacin
• linezolid
• quinupristin
• tigecycline

Other ID:

• GWAIDS0025751

UI: 102265375

From Meeting Abstracts