1. Academic Validation
  2. Activity of Oral Tebipenem-Avibactam in a Mouse Model of Mycobacterium abscessus Lung Infection

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

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.
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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