Systematic Review of Antimicrobial Combination Options for Pandrug-Resistant Acinetobacter baumannii

Abstract

Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.

Effectiveness and Nephrotoxicity of Loading Dose Colistin–Meropenem versus Loading Dose Colistin–Imipenem in the Treatment of Carbapenem-Resistant Acinetobacter baumannii Infection

“…An in vitro growth dynamics investigation also showed significant decreases in P. aeruginosa regrowth with a colistin-carbapenem combination, as well as a delay in the formation of colistinresistant subpopulations [22,23]. The proposed mechanism to explain the synergy between colistin and carbapenem indicates that colistin increases the permeability of the bacterial outer membrane, allowing more carbapenem to enter the bacteria [24]. Furthermore, larger concentrations of carbapenem can decrease the resistance mechanisms of the bacteria, making carbapenem more effective against drug-resistant bacteria [24].…”

Multidrug-Resistant Acinetobacter baumannii in Jordan

“…Pandrug-resistant A. baumannii infections are increasingly being reported worldwide and are associated with high mortality [ 29 ]. Treatment options for A. baumannii MDR are very limited and the evidence to guide treatment is lacking with combination therapy being recommended [ 30 , 31 ].…”

Cefiderocol: Systematic Review of Mechanisms of Resistance, Heteroresistance and In Vivo Emergence of Resistance

“…Extensively drug-resistant (XDR) and pandrug-resistant Gram-negative bacteria are increasingly being reported worldwide [ 1 ]. Attributable mortality appears to be high [ 2 ], and treatment options very limited [ 3 ], with synergistic combinations of in vitro inactive (alone) antimicrobials often being a last resort [ 3 , 4 , 5 ]. Cefiderocol appears promising, as it can overcome most of the mechanisms of β-lactam resistance (including β-lactamases, porin mutations and efflux pumps) [ 3 ].…”