azithromycin + ethambutol + rifampin + streptomycin

This is a four-drug combination regimen consisting of azithromycin, ethambutol, rifampin, and streptomycin. It is used primarily for the treatment of severe or refractory Mycobacterium avium complex pulmonary disease (MAC-PD) and other nontuberculous mycobacterial (NTM) lung infections. The standard therapy for MAC-PD typically includes a macrolide (azithromycin or clarithromycin), ethambutol, and rifampin; streptomycin is added in cases of extensive or fibrocavitary disease or when initial regimens have failed.

• Azithromycin is a macrolide antibiotic that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit.
• Ethambutol inhibits arabinosyl transferases involved in cell wall biosynthesis in mycobacteria.
• Rifampin inhibits DNA-dependent RNA polymerase in susceptible organisms, suppressing RNA synthesis. Its role in MAC-PD has been debated due to limited efficacy against M. avium but remains part of guideline-based regimens.
• Streptomycin is an aminoglycoside antibiotic that binds to the 30S ribosomal subunit, inhibiting protein synthesis; it is administered parenterally and reserved for severe cases due to toxicity concerns.