In vitro activity of teicoplanin combined with colistin versus multidrug-resistant strains of Acinetobacter baumannii

Abstract

Antimicrobial treatment of multidrug-resistant Acinetobacter baumannii (MDRAB) remains an important therapeutic challenge. With isolates resistant to all conventional agents now reported, clinicians are increasingly forced to turn to unorthodox combination treatments in the hope that these may be efficacious. Although a potent interaction between vancomycin and colistin has been demonstrated, there are concerns regarding the inherent toxicity of combining these agents in clinical practice. As teicoplanin has less nephrotoxic potential than vancomycin, we assessed whether a colistin/teicoplanin combination would have similar antimicrobial activities in vitro. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed versus a collection of MDRAB belonging to a number of epidemic lineages present in the UK. Synergy studies were undertaken using microtitre plate chequerboard assays, an Etest agar dilution method and standard time-kill methodology. The combination of teicoplanin and colistin was bactericidal versus all of the strains tested. In chequerboard assays, fractional inhibitory concentration indices of <0.5 were obtained, consistent with significant in vitro synergy. Using the Etest method the MIC of teicoplanin fell from >256 mg/L to ≤2 mg/L in the presence of subinhibitory concentrations of colistin. Significant synergy was observed when colistin was combined with teicoplanin versus MDRAB in vitro. This may represent a useful therapeutic combination for the treatment of A. baumannii infections, especially when renal toxicity is a significant concern.