Microbiological Outcomes of Oral Omadacycline Treatment in Adults with Nontuberculous Mycobacterial Pulmonary Disease (NTM-PD) Caused by Mycobacterium abscessus complex (MABc): Results from a Phase 2, Double-blind, Randomized, Placebo-controlled, Multi-center Trial

Background Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic disease commonly caused by Mycobacterium abscessus (MAB; previously M. abscessus complex; which is comprised of 3 subspecies: abscessus, massiliense, bolletii). Treatment of NTM-PD due to MAB is challenging due to intrinsic drug resistance, lack of effective oral antibiotics, and a need for complex, lengthy therapies. We describe microbiological endpoints from a double-blind, placebo-controlled clinical trial of oral omadacycline in NTM-PD due to MAB (NCT04922554).Figure 1.Negative M. abscessus sputum cultures (both broth and agar) at Day 84 (exploratory endpoint).Figure 2.Semi-quantitative sputum culture scores of M. abscessus in liquid media and on agar plates at baseline and post-baseline assessment points (exploratory endpoint).Scoring table adapted from: Griffith DE, et al. Am J Respir Crit Care Med. 2015 Sep 15;192(6):754-60. Methods Adults with NTM-PD caused by MAB were randomized 1.5:1 to receive 300 mg oral omadacycline monotherapy once daily (OMC, n=41) or placebo (PBO, n=25) for 84 days. Eligible patients met diagnostic criteria for MAB NTM-PD with no need for guideline-directed antibiotic therapy within 3 months and were excluded if they had antibiotic treatment for NTM in the prior 6 months, any systemic/inhaled antibiotic therapy (except chronic macrolides) within prior 4 weeks, cystic fibrosis, cavitary disease, or extrapulmonary NTM disease. Microbiological endpoints assessed negative sputum cultures (Day 84) and bacterial burden.Figure 3.Participants with M. abscessus growth in liquid medium only (SSC score=1) and no growth in agar at any timepoint (secondary endpoint).Figure 4.Mean time (days) to detection of M. abscessus growth in liquid media (exploratory endpoint).Error bars show 1 standard deviation. Results At Day 84, 58.8% of OMC-treated participants versus 29.2% of PBO-treated participants had negative sputum cultures (Figure 1). Semi-quantitative sputum culture (SSC) scores at baseline were similar for both cohorts; post-baseline at every timepoint, there was a greater decrease in score for OMC-treated participants versus PBO-treated participants (Figure 2). Overall, more participants in the OMC group had cultures that grew in liquid medium only with no growth in agar (SSC score=1) vs PBO at any timepoint (Figure 3). At baseline, mean time to detection (in days) of MAB growth in liquid media was similar in both cohorts (OMC, 4.4; PBO, 4.5) but at all other timepoints was longer in the OMC cohort versus PBO, respectively (Day 28, 7.1 vs. 4.8; Day 56, 5.7 vs. 4.8; Day 84, 6.5 vs. 5.4; Figure 4). Conclusion Treatment with OMC resulted in more negative cultures at Day 84 than PBO. Data suggest that OMC treatment decreased the mycobacterial burden of infection in patients with NTM-PD caused by MAB by a greater reduction in SSC scores, more participants with an SSC score=1 versus PBO, and longer time to positive cultures in liquid media. Disclosures All Authors: No reported disclosures