title: In vitro synergy of polymyxins with other antibiotics for Acinetobacter baumannii: a systematic review and meta-analysis.
abstract: In order to provide preliminary guidance for rational antibiotic combination therapy in the clinic, a systematic review and meta-analysis was performed to evaluate the in vitro synergistic activity of polymyxins combined with other antibiotics against Acinetobacter baumannii. An extensive literature search was undertaken without restriction according to region, publication type or language. All available in vitro synergy tests on antibiotic combinations consisting of polymyxins were included. The primary outcome assessed was the in vitro activity of combination therapy on bacterial kill or inhibition. In total, 70 published studies and 31 conference proceedings reporting testing of polymyxins in combination with 11 classes consisting of 28 antibiotic types against 1484 A. baumannii strains were included in the analysis. In time-kill studies, high in vitro synergy and bactericidal activity were found for polymyxins combined with several antibiotic classes such as carbapenems and glycopeptides. Carbapenems or rifampicin combination could efficiently suppress the development of colistin resistance and displayed a >50% synergy rate against colistin-resistant strains. Synergy rates of chequerboard microdilution and Etest methods in most antibiotic combinations were generally lower than those of time-kill assays. The benefits of these antibiotic combinations should be further demonstrated by well-designed clinical studies.
authors.affiliation: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Ni
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Di
authors.affiliation: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Junchang
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, Chinese People's Liberation Army General Hospital, Beijing 100853, China. Electronic address: liuyouningpla301@163.com.
authors.forename: Youning
authors.initials: Y
authors.lastname: Liu
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000502:physiology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D011113:Polymyxins / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins
keywords: Acinetobacter baumannii; Antibiotic combination; Polymyxin; Synergy