ethambutol + pyrazinamide + pretomanid + clofazimine

Ethambutol + pyrazinamide + pretomanid + clofazimine is an experimental four-drug combination regimen investigated for the treatment of tuberculosis (TB), particularly multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. This regimen, often referred to in preclinical literature as PaZEC, combines two established first-line antitubercular agents (ethambutol and pyrazinamide) with the novel nitroimidazole pretomanid and the repurposed riminophenazine clofazimine. The combination is designed to leverage multiple synergistic mechanisms: ethambutol inhibits cell wall synthesis by targeting arabinosyltransferases; pyrazinamide disrupts membrane potential and transport functions; pretomanid inhibits mycolic acid biosynthesis and induces respiratory poisoning through nitric oxide release; and clofazimine disrupts the bacterial membrane and respiratory chain while generating reactive oxygen species. While the individual components are clinically approved or in advanced clinical stages, this specific combination has primarily been evaluated in preclinical models, such as the murine model of TB, to assess its potential to shorten treatment duration and prevent the emergence of drug resistance.

Other names

PaZECethambutol + pyrazinamide + pretomanid + clofazimine