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

Author:

Negatu Dereje A12ORCID,Shin Sung Jae3,Kim Su-Young4,Jhun Byung Woo4,Dartois Véronique15ORCID,Dick Thomas156

Affiliation:

1. Center for Discovery and Innovation, Hackensack Meridian Health , Nutley, New Jersey , USA

2. Center for Innovative Drug Development and Therapeutic Trials for Africa, Addis Ababa University , Addis Ababa , Ethiopia

3. Department of Microbiology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine , Seoul , South Korea

4. Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , South Korea

5. Department of Medical Sciences, Hackensack Meridian School of Medicine , Nutley, New Jersey , USA

6. Department of Microbiology and Immunology, Georgetown University , Washington, District of Columbia , USA

Abstract

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.

Funder

National Institute of Allergy and Infectious Diseases, National Institutes of Health

Iterum

Therapeutics International, Ltd

Center for Discovery and Innovation

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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