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In Vivo Efficacy of Relebactam (MK-7655) in Combination with Imipenem-Cilastatin in Murine Infection Models

Mary Ann Powles1, Andrew Galgoci2, Andrew Misura2

  • 1Merck & Co., Inc., Kenilworth, New Jersey, USA maryann_powles@outlook.com.

Antimicrobial Agents and Chemotherapy
|June 6, 2018
PubMed

Insights

The new relebactam (REL) and imipenem-cilastatin (IMI) combination shows efficacy against multidrug-resistant bacteria. This study demonstrates IMI-REL

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Pharmacology

Background:

  • Antimicrobial resistance (AMR) is a significant global health threat, necessitating novel therapeutic strategies.
  • Carbapenem antibiotics are crucial for treating multidrug-resistant infections, but resistance is increasing.
  • Beta-lactamase inhibitors (BLIs) combined with beta-lactam antibiotics enhance activity against resistant bacteria.

Purpose of the Study:

  • To evaluate the in vivo efficacy of the imipenem-cilastatin (IMI)-relebactam (REL) combination.
  • To assess IMI-REL's effectiveness against imipenem-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae.
  • To investigate IMI-REL in various mouse infection models, including disseminated and pulmonary infections.

Main Methods:

  • In vivo efficacy studies were conducted using mouse models of disseminated and pulmonary infections.
  • Infections were caused by imipenem-resistant clinical isolates of P. aeruginosa and K. pneumoniae.
  • The IMI-REL combination was tested at different relebactam (REL) doses.

Main Results:

  • IMI-REL demonstrated significant efficacy in a disseminated infection model against P. aeruginosa and K. pneumoniae.
  • Log reductions in bacterial colony-forming units (CFUs) were observed in a dose-dependent manner for both pathogens.
  • The combination showed reduced efficacy in a delayed pulmonary infection model compared to immediate models.

Conclusions:

  • Relebactam (REL) effectively restored imipenem's activity against imipenem-resistant P. aeruginosa and K. pneumoniae in vivo.
  • The imipenem-cilastatin-relebactam (IMI-REL) combination is a promising therapeutic option for infections caused by these resistant strains.
  • Further research may explore optimal dosing and application in different infection scenarios.
Keywords:
Klebsiella pneumoniaePseudomonas aeruginosaimipenem resistantmultidrug resistancerelebactamβ-lactamase inhibitors

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