This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rand, K. H. Articles by Houck, H. J. Search for Related Content PubMed PubMed Citation Articles by Rand, K. H. Articles by Houck, H. J.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, August 2004, p. 2871-2875, Vol. 48, No. 8
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.8.2871-2875.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Synergy of Daptomycin with Oxacillin and Other ß-Lactams against Methicillin-Resistant Staphylococcus aureus

Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida 32610

Received 1 October 2003/ Returned for modification 4 November 2003/ Accepted 25 April 2004

We previously observed marked synergy between daptomycin and both rifampin and ampicillin against vancomycin-resistant enterococci (VRE). Because the synergy between daptomycin and ampicillin was observed for 100% of VRE strains with high-level ampicillin resistance (ampicillin MIC of 128 µg/ml), we looked for synergy between daptomycin and other ß-lactams against 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) by employing a time-kill method using Mueller-Hinton broth supplemented to 50 mg of Ca²⁺/liter. All strains were resistant to oxacillin (16 of 18 strains were resistant at drug concentrations of 256 µg/ml), and all strains were susceptible to daptomycin (the MIC at which 90% of the tested isolates were inhibited was 1 µg/ml). Daptomycin was tested at concentrations of 2, 1, 0.5, 0.25, 0.125, and 0.0625 µg/ml alone or in combination with oxacillin at a fixed concentration of 32 µg/ml. Synergy was found for all 18 strains with daptomycin at one-half the MIC in combination with 32 µg of oxacillin/ml, and synergy was found for 11 of 18 strains (61%) with daptomycin at one-fourth the MIC or less in combination with oxacillin. At 24 h, the daptomycin-oxacillin combination with daptomycin at one-half the MIC showed bactericidal activity against all 18 strains, and the combination with one-fourth the daptomycin MIC showed bactericidal activity against 9 of 18 strains. We also used a novel screening method to look for synergy between daptomycin and other ß-lactams. In this approach, daptomycin was incorporated into Ca²⁺-supplemented Mueller-Hinton agar at subinhibitory concentrations, and synergy was screened by comparing test antibiotic Kirby-Bauer disks on agar with and without daptomycin. By this method, daptomycin with ampicillin-sulbactam, ticarcillin-clavulanate, or piperacillin-tazobactam showed synergy comparable to or greater than daptomycin with oxacillin. For seven of the eight strains tested, time-kill studies confirmed synergy between daptomycin and ampicillin-sulbactam with ampicillin in the range of 2 to 8 µg/ml. The combination of daptomycin and ß-lactams may be useful for the treatment of MRSA infection, but further studies are needed to elucidate the mechanisms and to determine the in vivo efficacy of the combination.

This article has been cited by other articles:

• Warren, R. E. (2008). Daptomycin in endocarditis and bacteraemia: a British perspective. J Antimicrob Chemother 62: iii25-iii33 [Abstract] [Full Text]  
• Scheetz, M., Reddy, P., Postelnick, M., Flaherty, J. (2005). In vivo synergy of daptomycin plus a penicillin agent for MRSA?. J Antimicrob Chemother 55: 398-399 [Full Text]