Efficacy of drug regimens containing omadacycline in a murine model of Mycobacterium avium chronic lung infection
Abstract
Mycobacterium avium complex (MAC) is the most common non-tuberculous mycobacteria (NTM) and most frequent causative pathogen of NTM pulmonary infections. MAC is often associated with comorbidities, chronic infections, and high mortality rates. New treatment options are needed to increase treatment efficacy and tolerance. Omadacycline is a semisynthetic tetracycline-class drug with broad-spectrum activity, including against MAC in vitro . In an aerosol infection model of MAC pulmonary disease, we evaluated 9 treatment regimens that included omadacycline (OMC) alone or in dual, triple, or quadruple combinations with existing antibiotics: rifampin (RIF), clofazimine (CFZ), ethambutol (EMB), and clarithromycin (CLR). Treatment efficacy was assessed based on reduction of bacterial load in the lung and spleen over 4 months. OMC alone and OMC-RIF-EMB groups demonstrated efficacy starting at 2 months of treatment with a final reduction in bacterial burden in the lung of ~1 log 10 and >4 log 10 , respectively, compared with untreated mice. Omadacycline was as efficacious as rifampin in the standard-of-care regimen (CLR-RIF-EMB) over the first 3 months. The most potent combination tested in this study was OMC-CLR-CFZ, with a >5 log 10 reduction of bacterial burden in the lung. This is the first study demonstrating omadacycline efficacy against M. avium in mice alone and as part of a combination regimen. These data suggest that further evaluation of omadacycline for the treatment of…
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