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

Antimicrob Agents Chemother. 2017 Nov 22;61(12):e01239-17. doi: 10.1128/AAC.01239-17. Print 2017 Dec.

Abstract

Acinetobacter baumannii 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) A. baumannii strain. In standard in vitro 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.

Keywords: Acinetobacter; ESKAPE pathogens; animal models; antibacterial; antibiotic adjuvants; antibiotic resistance; antibiotics; mouse model; pulmonary model; virulent strain.

MeSH terms

  • Acinetobacter Infections / drug therapy*
  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / pathogenicity
  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Cross Infection / drug therapy*
  • Cross Infection / microbiology
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial
  • Mice
  • Microbial Sensitivity Tests
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Pneumonia, Ventilator-Associated / microbiology
  • Polymyxin B / therapeutic use*
  • Proof of Concept Study
  • Rifampin / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • NAB741
  • Polymyxin B
  • Rifampin