JAC Advance Access published online on November 22, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm459
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In vitro activities of tigecycline combined with other antimicrobials against multiresistant Gram-positive and Gram-negative pathogens
Laboratory of Infectious Diseases and Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland
Received 28 June 2007; returned 13 September 2007; revised 27 September 2007; accepted 29 October 2007
* Corresponding author. Tel: +41-21-692-5612; Fax: +41-21-692-5605; E-mail: jose.entenza{at}unil.ch
Objectives: To test the activity of tigecycline combined with 16 antimicrobials in vitro against 22 Gram-positive and 55 Gram-negative clinical isolates.
Methods: Antibiotic interactions were determined by chequerboard and time–kill methods.
Results: By chequerboard, of 891 organism–drug interactions tested, 97 (11%) were synergistic, 793 (89%) were indifferent and 1 (0.1%) was antagonistic. Among Gram-positive pathogens, most synergisms occurred against Enterococcus spp. (7/11 isolates) with the tigecycline/rifampicin combination. No antagonism was detected. Among Gram-negative organisms, synergism was observed mainly with trimethoprim/sulfamethoxazole against Serratia marcescens (5/5 isolates), Proteus spp. (2/5) and Stenotrophomonas maltophilia (2/5), with aztreonam against S. maltophilia (3/5), with cefepime and imipenem against Enterobacter cloacae (3/5), with ceftazidime against Morganella morganii (3/5), and with ceftriaxone against Klebsiella pneumoniae (3/5). The only case of antagonism occurred against one S. marcescens with the tigecycline/imipenem combination. Selected time–kill assays confirmed the bacteriostatic interactions observed by the chequerboard method. Moreover, they revealed a bactericidal synergism of tigecycline with piperacillin/tazobactam against one penicillin-resistant Streptococcus pneumoniae and with amikacin against Proteus vulgaris.
Conclusions: Combinations of tigecycline with other antimicrobials produce primarily an indifferent response. Specific synergisms, especially against enterococci and problematic Gram-negative isolates, might be worth investigating in in vitro models and/or in animal models simulating the human environment.
Key Words: glycylcycline , chequerboard , killing , indifference , synergism
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