SPR741, an Antibiotic Adjuvant, Potentiates the<i>In Vitro</i>and<i>In Vivo</i>Activity of Rifampin against Clinically Relevant Extensively Drug-Resistant Acinetobacter baumannii

Abstract

<i>Acinetobacter baumannii</i> is responsible for 10% of all nosocomial infections and has >50% mortality rates when causing ventilator-associated pneumonia. In this proof-of-concept study, we evaluated SPR741, an antibiotic adjuvant that permeabilizes the Gram-negative membrane, in combination with rifampin against AB5075, an extensively drug-resistant (XDR) <i>A. baumannii</i> strain. In standard <i>in vitro</i> assays and in a murine pulmonary model, we found that this drug combination can significantly reduce bacterial burden and promote animal survival despite an aggressive infection.