Systematic review and meta-analysis of in vitro efficacy of antibiotic combination therapy against carbapenem-resistant Gram-negative bacilli.

摘要: The superiority of combination therapy for carbapenem-resistant Gram-negative bacilli (CR-GNB) infections remains controversial. In vitro models may predict the efficacy antibiotic regimens against CR-GNB. A systematic review and meta-analysis was performed including pharmacokinetic/pharmacodynamic (PK/PD) time-kill (TK) studies examining in combinations CR-GNB [PROSPERO registration no. CRD42019128104]. primary outcome synergy based on effect size (ES): high, ES ≥ 0.75, moderate, 0.35 < 0.75; low, ≤ 0.35; absent, = 0). network assessed bactericidal re-growth rate (secondary outcomes). An adapted version ToxRTool used risk-of-bias assessment. Over 180 from 136 were included. most frequently analysed classes polymyxins carbapenems. Limited data available ceftazidime/avibactam, ceftolozane/tazobactam imipenem/relebactam. High or moderate synergism shown polymyxin/rifampicin Acinetobacter baumannii [ES 0.91, 95% confidence interval (CI) 0.44-1.00], polymyxin/fosfomycin Klebsiella pneumoniae (ES 1.00, CI 0.66-1.00) imipenem/amikacin Pseudomonas aeruginosa 0.21-1.00). Compared with monotherapy, increased activity lower rates reported colistin/fosfomycin K. imipenem/tobramycin P. aeruginosa. quality documented 65% 53% PK/PD TK studies, respectively. Well-designed should be encouraged to guide selection therapies clinical trials improve armamentarium bacteria.