title: In vitro effects of tigecycline in combination with colistin (polymyxin E) and sulbactam against multidrug-resistant Acinetobacter baumannii.
abstract: The lack of active antimicrobial agents against multidrug-resistant (MDR) Acinetobacter baumannii has posed great threat to the public health. Combination therapies with antibiotics owning different antimicrobial mechanisms have been proposed as good options for treating MDR A. baumannii infections. This study was aimed to investigate the in vitro effects of tigecycline in combination with colistin and sulbactam against MDR A. baumannii. A total of 70 strains from two hospitals in China were examined in the study. The checkerboard method was used for determining synergistic activity of different antibiotic combinations. Tigecycline/colistin combination displayed synergistic and partial synergistic activity in 24.3% of the isolates, whereas the tigecycline/sulbactam combination showed synergistic and partial synergistic activity in 64.3% of the isolates. Neither of the combinations showed antagonism in this study. In addition, for evaluating the ability of combinations on resistance prevention, mutant prevention concentrations (MPCs) of tigecycline, colistin, sulbactam alone and tigecycline in combination with colistin and sulbactam were studied against MDR A. baumannii. Compared with tigecycline used alone, combination therapies could achieve lower MPCs of tigecycline. However, when the MPCs of dual-drug therapy were in conjunction with clinical pharmacokinetic profiles, combinations may not strictly curb the occurrence of resistance at current dosage regimen. In summary, this study suggested that combination therapy was a good option for treating MDR A. baumannii infections. But the finding that combination with these drugs at current dosage regimen may not prevent emergence of resistance warranted further studies on dosage of combined antibiotics required for achieving resistance prevention.
authors: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Wentao
authors: W
authors: Ni
authors: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Junchang
authors: J
authors: Cui
authors: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Beibei
authors: B
authors: Liang
authors: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Yun
authors: Y
authors: Cai
authors: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Nan
authors: N
authors: Bai
authors: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Xuejiu
authors: X
authors: Cai
authors: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China.
authors: Rui
authors: R
authors: Wang
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002681:China; D003091:Colistin / Q000008:administration & dosage*; D024901:Drug Resistance, Multiple, Bacterial; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013407:Sulbactam / Q000008:administration & dosage*; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline; D013407:Sulbactam; D003091:Colistin