Determining In Vitro Synergistic Activities of tigecycline with Several Other Antibiotics against Brucella melitensis Using Checkerboard and Time-Kill Assays

Abstract

Antimicrobial therapy of Brucella spp. infection is difficult because there are relatively few effective treatment regimens, and single-agent therapy has generally been considered inadequate due to unacceptably high relapse rates. Tigecycline, the first in a new class of antimicrobials, the glycylcyclines, is a 9-t-butylglycylamido derivate of minocycline. In this study, the In Vitro activity of tigecycline in combination with gentamicin, streptomycin, rifampin, co-trimoxazole, levofloxacin, and minocycline was investigated using the checkerboard method to evaluate 16 Brucella melitensis isolates. The time-kill method was used to determine the bactericidal activities of combinations of tigecycline with rifampin, gentamicin, and levofloxacin, which were found (via the checkerboard method) to have a synergistic effect in combinations with tigecycline. Using the checkerboard method, combinations of rifampin, gentamicin, and levofloxacin with tigecycline showed synergistic effects against 5 (31.2%), 3 (18.9%), and 8 (50%) of the isolates. No synergy was observed with tigecycline in combination with minocycline, streptomycin, or cotrimoxazole. tigecycline with gentamicin achieved the earliest complete killing at 4× MIC (in 6 h), while complete killing with the other combinations was delayed up to 24 h. the time-kill method showed that the combination of tigecycline and levofloxacin had an antagonistic effect, while the checkerboard method detected synergy and no interaction effects. These data suggest that a combi-nation regimen of tigecycline with gentamicin and rifampin may be a good choice for treating brucellosis.

Keywords:

• Tigecycline
• brucellosis
• synergy
• checkerboard
• time-kill