Activity of Oral Tebipenem-Avibactam in a Mouse Model of Mycobacterium abscessus Lung Infection

  • Antimicrob Agents Chemother. 2023 Jan 23;e0145922. doi: 10.1128/aac.01459-22.
Dereje A Negatu  1  2 ,  Rubén González Del Río  3 ,  Mónica Cacho-Izquierdo  3 ,  David Barros-Aguirre  3 ,  Joël Lelievre  3 ,  Joaquín Rullas  3 ,  Patricia Casado  3 ,  Uday S Ganapathy  1 ,  Matthew D Zimmerman  1 ,  Martin Gengenbacher  1  4 ,  Véronique Dartois  1  4 ,  Thomas Dick  1  4  5
Affiliations
  • 1. Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.
  • 2. Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), Addis Ababa University, Addis Ababa, Ethiopia.
  • 3. Global Health Medicines R&D, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
  • 4. Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, New Jersey, USA.
  • 5. Department of Microbiology and Immunology, Georgetown University, Washington, DC, USA.
PMID: 36688684 DOI: 10.1128/aac.01459-22
Abstract

The combination of the β-lactam tebipenem and the β-lactamase inhibitor avibactam shows potent bactericidal activity against Mycobacterium abscessus in vitro. Here, we report that the combination of the respective oral prodrugs tebipenem-pivoxil and avibactam ARX-1796 showed efficacy in a mouse model of M. abscessus lung Infection. The results suggest that tebipenem-avibactam presents an attractive oral drug candidate pair for the treatment of M. abscessus pulmonary disease and could inform the design of clinical trials.

Keywords
ARX-1796; NTM; beta-lactam; beta-lactamase inhibitor; nontuberculous mycobacteria; tebipenem-pivoxil.
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