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Postantibiotic effect of colistin alone and combined with vancomycin or meropenem against Acinetobacter baumannii strains with well defined resistance mechanisms

ABSTRACT Colistin is now being administered as salvage therapy in patients in whom none of other antibiotics are active against their isolates. Previous studies found short postantibiotic effect of colistin on A. baumannii However, only a few studies have evaluated the potential for synergy between colistin and other antibiotics against A. baumannii. The aim of this study was to determine in vitro synergy and PAE of colistin combined with other antibiotics (vancomycin or meropenem) against carbapenem-resistant A. baumannii strains with defined resistance mechanisms. It was hypothesised that vancomycin or meropenem would prolog the PAE of colistin since it was previously found that they exert synergism with colistin in time-kill kinetics and chequerboard analysis. Meropenem exhibited synergy with colistin in chequerboard testing while vancomycin had better effect in time-kill analysis. Colistin alone exhibited negative (OXA-143), short (OXA- 24, OXA-58) or moderate PAE (OXA-23). When combined with vancomycin the PAE was moderate with OXA-23 and OXA-24 positive strains while with OXA-58 and OXA-143 positive strains it was not possible to calculate PAE because in two experiments there was no regrowth after exposure to antibiotics. The combination with meropenem resulted in short (OXA-143), moderate (OXA-24, OXA-58) or long PAE (OXA-23). From the clinical point of view, the prolongation of colistin PAE when combined with other antibiotics could provide a rationale for the modification of the dosing interval and could be important for the optimization of the treatment regimen and the minimization of drug- induced side effects. Furthermore, combined therapy could prevent development of heteroresistance in A. baumannii which often happens during colistin monotherapy

postanbiotic effect; Acinetobacter bauamannii; meropenem; colistin; vancomycin

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