Clinical Evaluation of Omadacycline for Pulmonary Mycobacterium abscessus Complex Infections: A Subgroup Analysis With a Focus on Macrolide Resistance.

BACKGROUND: Pulmonary infections caused by Mycobacterium abscessus complex (MABC) are notoriously difficult to treat due to high levels of mutational and inducible antibiotic resistance. Omadacycline (OMC), an aminomethylcycline antibiotic with both oral and IV formulations, has shown in vitro activity against MABC and may offer a more tolerable alternative to conventional therapies. However, clinical data specific to pulmonary MABC with macrolide resistance remain limited. The aim of this study was to evaluate the clinical and microbiological outcomes of OMC-based therapy in patients with pulmonary MABC infections. RESEARCH QUESTION: What are the clinical and microbiological outcomes of OMC-based therapy in patients with pulmonary MABC infections, including those with macrolide resistant isolates? STUDY DESIGN AND METHODS: This was a retrospective subgroup analysis of a previously published multicenter cohort study conducted across 16 US academic medical centers. Adult patients with pulmonary MABC infections who received OMC for ≥ 72 hours and had ≥ 3 months of follow-up were included. The primary outcome was clinical success at 3, 6, and 12 months, defined as a composite of clinical improvement, survival, continued OMC use, and absence of microbiologic recurrence. Secondary outcomes included sputum culture improvement, outcomes by MABC subspecies and macrolide susceptibility, and adverse drug reactions. RESULTS: Thirty-five patients were included (68.6% macrolide resistance). The median treatment duration was 8 months (interquartile range, 3.9-15.7). Clinical success was achieved in 71.4%, 89.7%, and 90.9% at 3, 6, and 12 months, respectively. Culture improvement occurred in 73.9% of evaluable patients, including 100% of those with macrolide-resistant strains. OMC was discontinued in 8 patients (22.9%) due to adverse drug reactions, most commonly gastrointestinal intolerance (26%) and transaminitis (11%). INTERPRETATION: Our results show that OMC demonstrated high clinical success and culture improvement rates in pulmonary MABC, including macrolide-resistant cases. These findings support its potential role as a tolerable and effective oral agent within multidrug regimens. Prospective studies are needed to confirm these results and define optimal use strategies.