Synergistic efficacy of tigecycline combined with apramycin against tet(X)-harboring Acinetobacter spp.

Abstract

The emergence of the wide variety of novel tigecycline resistance tet(X) variants including tet(X3), tet(X4), tet(X5) and tet(X6) has posed a significant challenge to the clinical treatment of multidrug-resistant bacterial infections and represents a serious threat to global public health. The purpose of this study was to evaluate the synergism of tigecycline combined with other antibiotics as a means of overcoming tet(X)-mediated resistance in Acinetobacter spp. We found that the combinations of tigecycline with apramycin or amikacin exhibited synergistic activity against tet(X)-harboring Acinetobacter spp. with FICI values of 0.088 and 0.625, respectively. The MICTGC decreased >5-fold decrease in the presence of subinhibitory levels of apramycin. This combination was shown to be a therapeutically effective synergism using both in vitro and in vivo (mouse thigh infection model) assays and delayed the increase of MIC values over time. This study highlights the synergism of tigecycline in combination with apramycin which offers a viable therapeutic alternative for infections caused by tet(X)-harboring Acinetobacter.