In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis.
OBJECTIVE
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.
Petersen
Peter J
PJ
Infectious Disease Discovery Research, Wyeth Research, Pearl River, NY 10965, USA.
Labthavikul
Ponpen
P
Jones
C Hal
CH
Bradford
Patricia A
PA
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078304:Tigecycline; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline