Invitro activity of imipenem-relebactam against gram-negative bacilli isolated from patients with lower respiratory tract infections in the United States in 2015 - Results from the SMART global surveillance program

Diagn Microbiol Infect Dis. 2017 Jun;88(2):171-176. doi: 10.1016/j.diagmicrobio.2017.02.018. Epub 2017 Mar 2.

Abstract

The β-lactamase inhibitor relebactam inactivates class A β-lactamases, including KPC-type carbapenemases, and class C β-lactamases. Relebactam combined with imipenem is in clinical development for several indications, including hospital-acquired and ventilator-associated pneumonia. Employing CLSI-defined broth microdilution methodology, we evaluated the activities of imipenem-relebactam (using imipenem MIC breakpoints) and comparators against non-Proteeae Enterobacteriaceae (n=853) and Pseudomonas aeruginosa (n=598) isolated from lower respiratory tract infection samples in 20 hospital laboratories in the United States participating in the 2015 SMART (Study for Monitoring Antimicrobial Resistance Trends) global surveillance program. Imipenem-relebactam and imipenem susceptibilities were 97.2% and 91.6% for non-Proteeae Enterobacteriaceae and 93.1% and 68.1% for P. aeruginosa. Relebactam restored imipenem susceptibility to 66.7% and 78.5% of imipenem-non-susceptible non-Proteeae Enterobacteriaceae isolates (n=72) and P. aeruginosa (n=191), respectively. Further development of imipenem-relebactam as therapy for lower respiratory tract infections is warranted given relebactam's ability to restore activity to imipenem against non-susceptible non-Proteeae Enterobacteriaceae and P. aeruginosa.

Keywords: Imipenem; Relebactam; Respiratory; SMART; Surveillance.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology*
  • Drug Therapy, Combination
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / drug therapy
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • Imipenem / pharmacology*
  • Microbial Sensitivity Tests
  • Pneumonia, Ventilator-Associated / drug therapy*
  • Pneumonia, Ventilator-Associated / microbiology
  • Pseudomonas Infections / drug therapy
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / isolation & purification
  • United States
  • beta-Lactamase Inhibitors / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • beta-Lactamase Inhibitors
  • Imipenem
  • relebactam