omadacycline and Lung-Diseases

First, omadacycline intrapulmonary concentration-time profiles of seven daily doses were mimicked in the HFS-Mab model and exposures associated with optimal efficacy were identified. Second, 10,000 subject Monte-Carlo simulations were performed to determine whether oral omadacycline 300 mg/day achieved these optimal exposures. Third, a retrospective clinical study on omadacycline vs. primarily tigecycline-based salvage therapy was conducted to assess rates of SSCC and toxicity. Fourth, a single patient was recruited to validate the findings.. Based on the preclinical and clinical data, omadacycline 300 mg/day in combination regimens could be appropriate for testing in Phase III trials in patients with Mab pulmonary disease.

Topics: Anti-Bacterial Agents; Humans; Lung Diseases; Microbial Sensitivity Tests; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Tetracyclines

Mycobacterium abscessus complex (MABSC) represents the second most common cause of nontuberculous mycobacterial pulmonary disease, associated with up to 17% of cases. Treatment of MABSC disease is complex, lengthy, and involves multidrug regimens due to high rates of intrinsic antimicrobial resistance; cure rates remain poor. There are currently no approved treatments for MABSC, and only limited data are available to guide treatment decisions for individual patients. Omadacycline, a tetracycline class-derived aminomethylcycline that is not approved for treatment of nontuberculous mycobacterial pulmonary infections, has been granted orphan drug designation by the US Food and Drug Administration. Here, we describe three cases using omadacycline as part of a first-line treatment regimen for patients with MABSC pulmonary infections, based on multiple factors, including resistance profile, toxicity, minimizing use of intravenous therapy, and expert recommendation. The clinical improvements of these patients, together with promising in vitro and early clinical development data, indicate that omadacycline warrants further investigation as a potential first-line option for incorporating into MABSC pulmonary disease treatment regimens.

Topics: Anti-Bacterial Agents; Humans; Lung Diseases; Mycobacterium abscessus; Mycobacterium Infections, Nontuberculous; Nontuberculous Mycobacteria; Tetracyclines