Evaluation of omadacycline against intracellular Mycobacterium abscessus in an infection model in human macrophages.
JAC Antimicrob Resist
; 5(5): dlad104, 2023 Oct.
Article
in En
| MEDLINE
| ID: mdl-37720564
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 3â 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 16â×â the MIC at 72â 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 16â×â 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Clinical_trials
Language:
En
Journal:
JAC Antimicrob Resist
Year:
2023
Type:
Article
Affiliation country:
United States