Determining in vitro synergistic activities of tigecycline with several other antibiotics against Brucella melitensis using checkerboard and time-kill assays

J Chemother. 2009 Feb;21(1):24-30. doi: 10.1179/joc.2009.21.1.24.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Brucella melitensis / drug effects*
  • Drug Synergism
  • Drug Therapy, Combination
  • In Vitro Techniques
  • Microbial Sensitivity Tests
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Tigecycline

Substances

  • Anti-Bacterial Agents
  • Tigecycline
  • Minocycline