Introduction

The emergence of Gram negative bacteria with increasingly multi-drug resistant profiles has become a serious public health concern worldwide, with isolates commonly reported resistant to carbapenems. However, no totally new class of antibiotics active against Gram negative bacteria has been introduced for over 40 years. One of the most significant barriers to the development of novel anti-Gram negative agents is the bacterial outer membrane. One novel therapeutic approach is to combine an antibiotic with a “potentiator” molecule that permeabilises the outer membrane, granting antibiotics that would otherwise be ineffective, access to their targets. SPR741, a cationic peptide derived from polymyxin B, is one such potentiator molecule that is under development for the treatment of serious Gram negative bacterial infections. Here, we show that SPR741 substantially enhances the in vitro efficacy of several conventional antibiotics against E. coli, K. pneumoniae, and A. baumannii.

_{1 Evotec (UK) Ltd, Manchester, United Kingdom}

_{2 Spero Therapeutics, Cambridge, MA}

_{3 Northern Antibiotics Ltd, Espoo, Finland}