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

Previous studies found short postantibiotic effect of colistin on A. baumannii. Many 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. After exposure of 1 h colistin alone exhibited the negative (-0.07 h) (OXA-143), short (0.2- 1, 82 h) (OXA-24, OXA-58, OXA-72, VIM-1+OXA-23, OXA- 58+NDM-1, ISAba1/OXA-69) or moderate PAE (3.2 h) for OXA-23 positive strain. When combined with vancomycin, the PAE was moderate (1.7-4 h) with OXA-23, OXA-23+VIM-1, OXA-72 and OXA-24 positive strains while with OXA-58, OXA-143, OXA-58/NDM-1 and ISAba1/OXA-69 positive strains it was not possible to calculate mean duration of PAE because there was no regrowth after exposure to antibiotics or it was longer than five hours as shown in Fig 1. The combination with meropenem resulted in short (0.2 h) (OXA- 143), moderate (2.4-3.73 h) (OXA-24, OXA-58, OXA-23, OXA-23+VIM-1), or long PAE of 5 h (OXA- 23) or longer than 5 h (OXA-58+VIM-1, ISAba1/OXA-69). 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.

Acinetobacter baumannii ; postantibiotic effect ; in vitro synergism ; vancomycin ; meropenem

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