Oral β-Lactam Pairs for the Treatment of Mycobacterium avium Complex Pulmonary Disease

J Infect Dis. 2024 Aug 16;230(2):e241-e246. doi: 10.1093/infdis/jiad591.

Abstract

Cure rates for pulmonary disease caused by the Mycobacterium avium complex (MAC) are poor. While β-lactam are front line antibiotics against Mycobacterium abscessus pulmonary disease, they have not been used or recommended to treat MAC lung infections. Through a comprehensive screen of oral β-lactams, we have discovered that selected pairs combining either a penem/carbapenem or penicillin with a cephalosporin are strongly bactericidal at clinically achieved concentrations. These dual β-lactam combinations include tebipenem and sulopenem, both in phase 3, and Food and Drug Administration-approved amoxicillin and cefuroxime. They could therefore immediately enter clinical trials or clinical practice.

Keywords: Mycobacterium avium complex; amoxicillin; cefuroxime; nontuberculous mycobacteria; sulopenem; synergy; target attainment; tebipenem; β-lactam.

MeSH terms

  • Administration, Oral
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / therapeutic use
  • Humans
  • Lung Diseases / drug therapy
  • Lung Diseases / microbiology
  • Microbial Sensitivity Tests
  • Mycobacterium avium Complex* / drug effects
  • Mycobacterium avium-intracellulare Infection* / drug therapy
  • Mycobacterium avium-intracellulare Infection* / microbiology
  • beta-Lactams* / administration & dosage
  • beta-Lactams* / therapeutic use

Substances

  • beta-Lactams
  • Anti-Bacterial Agents