Overcoming (X)-harboring tigecycline resistance: a study on the efficacy of tigecycline-apramycin combinations.

INTRODUCTION

The emergence of the wide variety of novel tigecycline resistance (X) variants, including (X3), (X4), (X5), and (X6), has raised a serious threat to global public health and posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections.

METHODS

In this study, we evaluated the synergism of tigecycline combining with other antibiotics as a means of overcoming the (X)-mediated resistance in spp. Antibiotic synergistic efficacy was evaluated through chequerboard experiments, time-kill assays and dose-response curves. The synergistic effect of the combination was confirmed in a mouse model of thigh with neutrophilic granulocyte reduction. Additionally, combinations were tested for their ability to prevent high-level tigecycline-resistant mutants.

RESULTS

We found that the combinations of tigecycline with apramycin exhibited synergistic activity against (X)-harboring Acinetobacter spp. with FICI of 0.088. The MICTGC decreased more than 5 times in the presence of subinhibitory levels of apramycin. The combination showed in vitro synergism in time-kill assays and in vivo therapeutic effectiveness in the mouse thigh infection model.

DISCUSSION

This study shed light on the synergism of tigecycline in combination with apramycin which offers a viable therapeutic alternative for infections caused by (X)-harboring spp.