In vitro activities of tigecycline combined with other antimicrobials against multiresistant Gram-positive and Gram-negative pathogens

• Published in: Journal of antimicrobial chemotherapy 2008-02, Vol.61 (2), p.371-374
• Main Authors: Vouillamoz, Jacques, Moreillon, Philippe, Giddey, Marlyse, Entenza, José M.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - administration & dosage; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chemotherapy; chequerboard; Comparative studies; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - physiology; Drug Therapy, Combination; Enterobacter cloacae; Enterococcus; glycylcycline; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - physiology; Gram-Positive Bacteria - drug effects; Gram-Positive Bacteria - physiology; Humans; indifference; killing; Klebsiella pneumoniae; Medical sciences; Microbial Sensitivity Tests - methods; Microbiology; Minocycline - administration & dosage; Minocycline - analogs & derivatives; Morganella morganii; Pharmacology. Drug treatments; Proteus vulgaris; Serratia marcescens; Stenotrophomonas maltophilia; Streptococcus pneumoniae; synergism
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkm459

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.