SPR720 + azithromycin + ethambutol

A combination therapy consisting of **SPR720**, **azithromycin**, and **ethambutol** under investigation for treating nontuberculous mycobacterial pulmonary disease (NTM-PD) and considered for tuberculosis therapy. SPR720 is an orally administered phosphate ester prodrug which is rapidly converted in vivo to SPR719, an aminobenzimidazole that inhibits the ATPase site of bacterial DNA gyrase B—a novel mechanism distinct from fluoroquinolones[1][3][5]. Azithromycin is a macrolide antibiotic inhibiting bacterial protein synthesis via binding to the 50S ribosomal subunit. Ethambutol inhibits arabinosyl transferase, affecting cell wall synthesis in mycobacteria. This combination aims to leverage the distinct mechanisms to enhance efficacy and limit resistance in pulmonary infections due to mycobacteria. Trials have evaluated the combination in both monotherapy and combination regimens[6][3].