Introduction

The spread of multi-drug resistant Gram-negative bacteria appears unstoppable. In some localities, bacteria resistant to all available antibiotics are causing infections, effectively taking us back to the pre-antibiotic era.

The Gram-negative bacterial cell membrane acts as a barrier to the entry of many antimicrobial agents, rendering the bacteria resistant or at best only weakly susceptible to a potentially useful antimicrobial agent. An attractive approach to addressing the lack of treatment options is potentiation of antimicrobial agents to either increase the spectrum of activity or enhance activity.

In these studies, the combination of the cationic peptide SPR741 and rifampicin was assessed in neutropenic murine models of thigh muscle infection due to a range of susceptible and MDR Enterobacteriaceae and Acinetobacter baumannii. The studies were short duration to enable optimum dosing in terms of PK profile.

_{1 Evotec (UK) Ltd, Manchester, UK} 

_{2 Spero Therapeutics, Cambridge, MA, USA}