In vitro activities of tigecycline combined with other antimicrobials against multiresistant gram-positive and gram-negative pathogens.
OBJECTIVE
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.
Vouillamoz
Jacques
J
Laboratory of Infectious Diseases and Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, CH-1015 Lausanne, Switzerland.
Moreillon
Philippe
P
Giddey
Marlyse
M
Entenza
José M
JM
D000890:Anti-Infective Agents / Q000008:administration & dosage*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000078304:Tigecycline
D000890:Anti-Infective Agents; D000078304:Tigecycline; D008911:Minocycline