Determining in vitro synergistic activities of tigecycline with several other antibiotics against Brucella melitensis using checkerboard and time-kill assays.
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 co-trimoxazole. tigecycline with gentamicin achieved the earliest complete killing at 4x 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 combination regimen of tigecycline with gentamicin and rifampin may be a good choice for treating brucellosis.
Aliskan
H
H
Department of Microbiology and Clinical Microbiology, Baskent University Faculty of Medicine, Ankara, Turkey.
Can
F
F
Demirbilek
M
M
Colakoglu
S
S
Kilic
S
S
Arslan
H
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017347:Brucella melitensis / Q000187:drug effects*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline