Evaluation of omadacycline against intracellular Mycobacterium abscessus in an infection model in human macrophages

Abstract Background Omadacycline is an aminomethylcycline antibiotic in the tetracycline class that was approved by the US FDA in 2018 for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. It is available in both IV and oral formulations. Omadacycline has broad-spectrum in vitro activity and clinical efficacy against infections caused by Gram-positive and Gram-negative pathogens. Omadacycline is being evaluated in a 3 month placebo-controlled Phase 2 clinical trial of oral omadacycline versus placebo in adults with non-tuberculous mycobacteria (NTM) pulmonary disease caused by Mycobacterium abscessus (NCT04922554). Objectives To determine if omadacycline has intracellular antimicrobial activity against NTM, bacteria that can cause chronic lung disease, in an ex vivo model of intracellular infection. Methods Two strains of M. abscessus were used to infect THP-1 macrophages. Intracellular M. abscessus was then challenged with omadacycline and control antibiotics at multiples of the MIC over time to evaluate intracellular killing. Results At 16 × the MIC at 72 h, omadacycline treatment of intracellular NTM yielded a log10 reduction in cfu of 1.1 (91.74% reduction in cfu) and 1.6 (97.65% reduction in cfu) consistent with killing observed with tigecycline, whereas amikacin and clarithromycin at 16 × the MIC did not show any reduction in cfu against the intracellular M. abscessus. Conclusions Omadacycline displayed intracellular activity against M. abscessus within macrophages. The activity was similar to that of tigecycline; as expected, intracellular killing was not observed with clarithromycin and amikacin.