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JAC Advance Access originally published online on October 12, 2009
Journal of Antimicrobial Chemotherapy 2009 64(6):1130-1138; doi:10.1093/jac/dkp346
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Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Review

Effects of daptomycin in combination with other antimicrobial agents: a review of in vitro and animal model studies

Judith N. Steenbergen*, John F. Mohr and Grace M. Thorne

Cubist Pharmaceuticals, Inc., Lexington, MA 02421, USA

* Corresponding author. Tel: 01-781-860-8300; Fax: 01-781-860-1234; E-mail: judith.steenbergen{at}cubist.com

This review summarizes the in vitro and animal model data available on antibiotic combinations with daptomycin. The majority of studies focus on the clinically relevant combinations of daptomycin with rifampicin or with gentamicin. These studies demonstrate that daptomycin does not adversely affect the activity of other antimicrobial agents that may be administered concomitantly. Overall, additive or indifferent effects with daptomycin combinations were observed; however, synergy was observed for certain isolates of vancomycin-resistant enterococci when exposed to daptomycin and rifampicin. Unexpected synergy was demonstrated against methicillin-resistant Staphylococcus aureus by daptomycin and β-lactams. Most importantly, no in vitro antagonism of daptomycin with any other agent tested was confirmed in these studies. The most striking in vivo effects were noted in two different complicated infection models; i.e. osteomyelitis and implant infections, where rifampicin combinations with daptomycin increased efficacy and reduced the incidence of rifampicin resistance.

Keywords: antimicrobials , gentamicin , rifampicin , vancomycin


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