In vivo efficacy of glycopeptide-colistin combination therapies in a Galleria mellonella model of Acinetobacter baumannii infection

Abstract

The treatment of Acinetobacter baumannii infections poses a significant clinical challenge, with isolates resistant to all commonly used agents increasingly being reported. With few new agents in the pipeline, clinicians are increasingly turning to combinations of antimicrobials in the hope that they may act synergistically together. In this study we assessed the activities of two glycopeptide-colistin combinations both in vitro and using a Galleria mellonella caterpillar model of A. baumannii infection. In checkerboard assays both vancomycin and teicoplanin were highly active against susceptible and multidrug-resistant strains of A. baumannii when combined with colistin (fractional inhibitory concentration [FIC] of <0.25). Treatment of G. mellonella caterpillars infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when either vancomycin or teicoplanin was given with colistin compared to colistin treatment alone (P < 0.05). This effect was most marked when vancomycin was the glycopeptide administered, although this agent was also highly effective as monotherapy, possibly through an immunomodulatory action on the G. mellonella response to A. baumannii infection. This work suggests that glycopeptide-colistin combinations are highly active against A. baumannii both in vitro and in a simple animal model of infection. They should be considered further as potential treatments for difficult-to-treat A. baumannii infections.

Fig. 1.

Kill kinetics of A. baumannii ATCC 19906 (A) and AB210 (B) in G. mellonella larvae over 96 h. Curves represent a single experiment performed using 10 insects.

Fig. 2.

Survival curves for A. baumannii ATCC 19606 (A) and AB210 (B) following treatment with colistin (COL), gentamicin (GENT), teicoplanin (TEIC), or PBS alone. Curves represent a single experiment performed using 16 insects.

Fig. 3.

Survival of A. baumannii ATCC 19606 (A) and AB210 (B) following treatment with colistin (COL) in combination with teicoplanin (TEIC) or vancomycin (VANC). For ATCC 19606, P < 0.001 for TEIC-COL and VANC-COL versus PBS; for AB210, P < 0.001 for VANC-COL and P < 0.05 for TEIC-COL versus PBS. Curves represent a single experiment performed using 16 insects.

Fig. 4.

Effect of vancomycin (VANC) treatment on ATCC 19606 (P < 0.001)- and AB210 (P < 0.01)-infected caterpillars. Curves represent a single experiment performed using 16 insects.