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

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. Graphical Abstract Graphical Abstract Oral β-lactam pairs combining tebipenem, sulopenem, or amoxicillin with cefuroxime achieve strong bactericidal activity at recommended doses against pulmonary disease caused by the Mycobacterium avium complex.