MERCIER R, MAZZOLA J, DIETZ R; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. A-500.

University of New Mexico - College of Pharmacy, Albuquerque, NM

BACKGROUND: Staphylococcus aureus (SA) is well known for its virulence and ability to cause endovascular infections. SA intermediately resistant to glycopeptides have been reported and increased resistance is predictable in the future. Agents with activity against multi-drug resistant gram-positive bacteria are further needed. We investigated the pharmacodynamic properties of tigecycline against SA infected simulated endocardial vegetations (SEVs). METHODS: Four strains of SA differing either in their susceptibility to methicillin: MRSA-494, MSSA-1199; or resistance pattern to tetracyclines: MSSA tet[(K)], MSSA tet[(M)], were used. Tigecycline was compared to vancomycin in an in vitro model of IE using a starting inoculum of 10[9] CFU/g. Tigecycline was dosed to simulate a 100mg bolus (peak: 2.9 microg/ml) followed by 50mg IV q12h (peak: 0.9 microg/ml) and vancomycin simulated a 1g IV q12h dosing (peak of 30 microg/ml). The model mimicked a t[1/2] of 30h for tigecycline and 8h for vancomycin. Bacterial densities in the SEVs were quantified and compared at 72h using ANOVA. RESULTS: Tigecycline and vancomycin MICs (microg/ml) for MRSA 494, MSSA 1199, MSSA tet[(K)] and MSSA tet[(M)] were 0.25/0.50; 0.13/1.0; 0.50/1.0; 0.06/1.0, respectively. Tigecycline significantly inhibited the growth of all SA isolates regardless of their susceptibilities to methicillin or tetracyclines (P<0.05). Vancomycin inhibited bacterial growth of tet[(M)] significantly greater than tigecycline. Tigecycline was more potent against MSSA as opposed to MRSA (P<0.05). Tigecycline displayed a similar antibacterial effect against MRSA-494 as vancomycin (P>0.05). Conclusion: Despite the presence of a high inoculum and the fibrin-platelet matrix harboring the bacteria, tigecycline demonstrated potent antimicrobial effects against all SA strains tested. Tigecycline had similar growth inhibitory effects as vancomycin against MRSA-494 establishing its role as a potential new agent in the treatment of drug resistant bacteria.

Publication Types:

• Meeting Abstracts

Keywords:

• Anti-Bacterial Agents
• Endocarditis, Bacterial
• Gram-Positive Bacteria
• In Vitro
• Minocycline
• Staphylococcal Infections
• Staphylococcus aureus
• Vancomycin
• Vancomycin Resistance
• methods
• tigecycline

Other ID:

• GWAIDS0027617

UI: 102267241

From Meeting Abstracts