Synergistic efficacy of β-lactam combinations against mycobacterium abscessus pulmonary infection in mice

Elizabeth Story-Roller, Emily C. Maggioncalda, Gyanu Lamichhane

Research output: Contribution to journalArticle

Abstract

Mycobacterium abscessus is an emerging pathogen capable of causing invasive pulmonary infections in patients with chronic lung diseases. These infections are difficult to treat, necessitating prolonged multidrug therapy, which is further complicated by extensive intrinsic and acquired resistance exhibited by clinical M. abscessus isolates. Therefore, development of novel treatment regimens effective against drug-resistant strains is crucial. Prior studies have demonstrated synergistic efficacy of several β-lactams against M. abscessus in vitro; however, these combinations have never been tested in an animal model of M. abscessus pulmonary disease. We utilized a recently developed murine system of sustained M. abscessus lung infection delivered via an aerosol route to test the bactericidal efficacy of four novel dual β-lactam combinations and one β-lactam/β-lactamase inhibitor combination. All five of the novel combinations exhibited synergy and resulted in at least 6-log10 reductions in bacterial burden in the lungs of mice at 4 weeks compared to untreated controls (P=0.038).

Original languageEnglish (US)
Article numbere00614-19
JournalAntimicrobial agents and chemotherapy
Volume63
Issue number8
DOIs
StatePublished - Jan 1 2019

Keywords

  • Mycobacterium abscessus
  • Synergy
  • β-lactams

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Synergistic efficacy of β-lactam combinations against mycobacterium abscessus pulmonary infection in mice'. Together they form a unique fingerprint.

  • Cite this