Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.
Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC) for meropenem (MIC ≤ 32 mg/L), combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.
Clinical Laboratory of South Building, Chinese People's Liberation Army General Hospital, Beijing 100853, China.|Clinical Laboratory of the Second Clinical District, the General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China.
Bing
B
Fan
Department of Clinical Laboratory, Peking University First Hospital, Beijing 100034, China.
Jie
J
Guan
Department of Clinical Laboratory, the General Hospital of Chinese People's Armed Police Forces, Beijing 100039, China.
Xiumei
X
Wang
Clinical Laboratory of South Building, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Yulong
Y
Cong
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D000818:Animals; D003091:Colistin / Q000494:pharmacology; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics*; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology; D005672:Fusidic Acid / Q000494:pharmacology; D000077731:Meropenem; D051379:Mice; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D013407:Sulbactam / Q000494:pharmacology; D013845:Thienamycins / Q000494:pharmacology; D000078304:Tigecycline
D004338:Drug Combinations; D013845:Thienamycins; D005578:Fosfomycin; D005672:Fusidic Acid; D000078304:Tigecycline; D000077731:Meropenem; D008911:Minocycline; D013407:Sulbactam; D012293:Rifampin; D003091:Colistin