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JAC Advance Access originally published online on January 23, 2006
Journal of Antimicrobial Chemotherapy 2006 57(3):573-576; doi:10.1093/jac/dki477
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© The Author 2006. 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

In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis

Peter J. Petersen, Ponpen Labthavikul, C. Hal Jones* and Patricia A. Bradford

Infectious Disease Discovery Research, Wyeth Research, Pearl River, NY 10965, USA

Received 7 October 2005; returned 16 November 2005; revised 30 November 2005; accepted 12 December 2005

* Corresponding author. Tel: +1-845-602-4612; Fax: +1-845-602-5671; E-mail: jonesh3{at}wyeth.com

Objectives: This study was undertaken to determine the interaction of tigecycline with 13 select antimicrobial agents against a wide variety of Gram-negative and Gram-positive bacterial isolates.

Methods: Antibiotic interactions were assayed using the chequerboard MIC format and selected synergistic combinations were confirmed using time-kill kinetic analysis.

Results: Microdilution chequerboard analysis of tigecycline in combination with amikacin, ampicillin/sulbactam, azithromycin, ciprofloxacin, colistin, imipenem, levofloxacin, piperacillin, piperacillin/tazobactam, polymyxin B, rifampicin, minocycline and vancomycin resulted in an interpretation of either no interaction or synergy. Time-kill kinetic analysis resulted in an interpretation of no interaction for all but one of the drug combinations that resulted in an interpretation of synergy by the chequerboard analysis. Antagonism was not observed for any combination when assayed by either method.

Conclusions: The lack of antagonism seen with tigecycline combinations in both chequerboard and time-kill kinetic studies is an encouraging outcome, suggesting that tigecycline may prove to be effective in combination therapy as well as in monotherapy.

Keywords: antibiotics , synergy , antagonism , susceptibility


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