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

Abstract number: P1866

Aliskan H., Can F., Demirbilek M., Colakoglu S., Arslan H.

Objectives: Antimicrobial therapy of Brucella spp. infection is difficult because there are relatively few effective treatment regimens, and single-agent therapy frequently fails clinically. Assessing the killing activity and the effect of combination therapy (synergistic or antagonistic) is important for antibiotics used to treat brucellosis.

Methods: In this study, the in vitro activity of tigecycline in combination with gentamicin, streptomycin, rifampin, co-trimoxazole, levofloxacin, and minocycline was investigated with the chequerboard method in 16 Brucella melitensis isolates. The time-kill method was used to determine bactericidal activities of combinations of tigecycline with rifampin, gentamicin, and levofloxacin, which were found to have a synergistic effect in combination with tigecycline.

Results: Using the chequerboard method, combinations of rifampin, gentamicin, and levofloxacin with tigecycline yielded synergy in 31.2%, 18.9%, 50% of the isolates respectively. No synergism was observed between combinations of minocycline, streptomycin, and co-trimoxazole with tigecycline by the chequerboard method.

Time-kill results showed that tigecycline+gentamicin achieved the fastest complete killing within 6 h and created a synergy as shown by the chequerboard method. Although rifampin alone caused complete killing within 48 h at MIC, rifampin+tigecycline combination exhibited faster killing only within 24 h. In this study, the time-kill method showed that tigecycline in combination with levofloxacin had an antagonism, while the chequerboard method showed that they had synergy and no interaction effects. Tigecycline alone caused complete killing within 24 h at MIC and was the fastest acting agent.

Conclusion: The chequerboard method revealed that three antibiotic combinations (tigecycline+gentamicin, tigecycline+rifampin, and tigecycline+levofloxacin) had a synergistic activity. Although tigecycline+gentamicin and tigecycline+rifampin synergistic activities were confirmed by the time-kill method, the opposite effect was determined with tigecycline+levofloxacin combination. Several investigators have found discord between the chequerboard and time-kill methods, agreement ranges between 44% and 88% and the time-kill method to be a reliable predictor of in vivo synergy. It appears that the combinations of tigecycline+rifampin and tigecycline+gentamicin may be used to treat brucellosis.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Location: Barcelona, Spain
Presentation type:
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