Bedaquiline Eliminates Bactericidal Activity of ß-Lactams against Mycobacterium abscessus.

The ß-lactams imipenem and cefoxitin are used for the treatment of Mycobacterium abscessus lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of M. abscessus with the antimycobacterial ATP synthase inhibitor bedaquiline suppresses this ATP burst and eliminates the bactericidal activity of ß-lactams. Thus, the addition of bedaquiline to ß-lactam-containing regimes may negatively affect treatment outcome.