Synergy against extensively drug-resistant Acinetobacter baumannii in vitro by two old antibiotics: colistin and chloramphenicol.
Combination antimicrobial therapy is an important option in the fight against Gram-negative 'superbugs'. This study systematically investigated the synergistic effect of colistin (CST) and chloramphenicol (CHL) in combination against extensively drug-resistant Acinetobacter baumannii (XDR-AB). The microtitre plate chequerboard assay was used to test synergy against 50 XDR-AB clinical strains. Then, three XDR-AB clinical isolates and the type strain A. baumannii ATCC 19606 were chosen for further synergy studies using time-kill assay, mutant prevention concentration (MPC) assay and real-time population analysis profile (PAP) assay. In the chequerboard assays, synergistic or additive effects [defined as a fractional inhibitory concentration index (FICI) of ≤0.5 and 0.5 < FICI < 1, respectively] were observed in all 50 isolates. In further synergy testing, the results of time-kill assays indicated that CST monotherapy produced rapid bacterial killing followed by rapid re-growth, with the emergence of CST resistance; CHL monotherapy was largely ineffective. The combination CST/CHL, however, showed a synergistic effect and enhanced bacterial killing in the four tested strains. It also significantly delayed re-growth and suppressed the emergence of CST resistance. In the MPC assay, a decrease in MPCs for CST was observed in the two CST-susceptible strains. PAP assay showed that both CST-resistant strains were heteroresistant.
Department of Microbiology and Immunology, Southeast University School of Medicine, Nanjing, China.
Wen-Juan
WJ
Wei
Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: younghaifei@gmail.com.
Hai-Fei
HF
Yang
D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D006801:Humans; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002701:Chloramphenicol; D003091:Colistin
Acinetobacter baumannii; Antimicrobial synergy; Chloramphenicol; Colistin