title: A meta-analysis of in vitro antibiotic synergy against Acinetobacter baumannii.
abstract: The aim of the work was to describe the different in vitro models for testing synergism of antibiotics and gather the results of antibiotic synergy against multidrug-resistant Acinetobacter baumannii (MDR-Ab). The different original articles were obtained from different web sites. In order to compare the results obtained by the different methods for synergy testing, the Pearson chi-square and the Fischer tests were used. Moreover, non-parametric chi-square test was used in order to compare the frequency distribution in each analysed manuscript. In the current meta-analysis 24 manuscripts, which encompassed 2016 tests of in vitro synergism of different antimicrobials against MDR-Ab, were revised. Checkerboard synergy testing was used in 11 studies, which encompasses 1086 tests (53.9%); time-kill assays were applied in 12 studies, which encompass 359 tests (17.8%); gradient diffusion methods were used in seven studies, encompassing 293 tests (14.5%). And, finally, time-kill plus checkerboard were applied in two studies, encompassing 278 tests (13.8%). By comparing these data, checkerboard and time-kill methods were significantly more used than gradient diffusion methods (p<0.005). Regarding synergy rates obtained on the basis of the applied method, checkerboard provided 227 tests (20.9%) with a synergistic effect; time-kill assays yielded 222 tests (61.8%) with a synergistic effect; gradient diffusion methods only provided 29 tests (9.9%) with a synergistic effect; and, finally, time-kill plus checkerboard yielded just 15 tests (5.4%) with a synergistic effect. When comparing these percentages, synergy rates reported by time-kill methods were significantly higher than that obtained by checkerboard and gradient diffusion methods (p<0.005). On the basis of the revised data, the combinations of a bactericidal antibiotic plus Tigecycline, Vancomycin or Teicoplanin are not recommended. The best combinations of antibiotics are those which include bactericidal antibiotics such as Carbapenems, Fosfomycin, Amikacin, Polymyxins, Rifampicin and Ampicillin/Sulbactam.
authors.affiliation: Service of Microbiology and Immunology, University Clinic Hospital of Valladolid, Ramón y Cajal Avenue n°3, 47003, Valladolid, Spain. Electronic address: gmr810@hotmail.com.
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: March
authors.affiliation: Service of Microbiology and Immunology, University Clinic Hospital of Valladolid, Ramón y Cajal Avenue n°3, 47003, Valladolid, Spain; Department of Microbiology, Faculty of Medicine, University of Valladolid, Av. Ramón y Cajal n°7, 47005, Valladolid, Spain. Electronic address: bratos@med.uva.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Bratos
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D008826:Microbial Sensitivity Tests
chemical_list: D000900:Anti-Bacterial Agents
keywords: Acinetobacter baumannii; Antibiotic combinations; Synergy testing