In Vitro Susceptibility Testing of Omadacycline against Nontuberculous Mycobacteria

Infections caused by nontuberculous mycobacteria (NTM) are increasing globally. Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex are the most frequently encountered NTM, and oral treatment options are extremely limited for these pathogens, especially for the M. abscessus complex. In this study, the in vitro potency of omadacycline, a new tetracycline derivative, was tested against 111 isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 70 isolates of rapidly growing mycobacteria (RGM), of which >90% were tetracycline resistant. These included M. abscessus subsp. abscessus (20 isolates), M. abscessus subsp. massiliense (3), Mycobacterium chelonae (15 isolates), Mycobacterium immunogenum (7 isolates), the Mycobacterium fortuitum group, including six doxycycline-resistant isolates (12 isolates), and the Mycobacterium mucogenicum group, including four doxycycline-resistant isolates (10 isolates). Forty-one isolates of slowly growing mycobacteria (SGM), including 16 isolates of MAC, were also tested. Omadacycline was active against all RGM species, with MIC sa ranges of 0.004 to 025 and 0.06 to 1 mu g/ml for 80% and 100% inhibition, respectively. For M. abscessus subsp. abscessus, MIC(50)s were 0.06 and 0.12 mu g/ml with 80% and 100% inhibition, respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs of tigecycline exhibited no trailing and were generally within 1 to 2 dilutions of the 100% inhibition omadacycline MICs. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range, 8 to >16 mu g/ml; n =41), as previously noted with tigecycline. This study supports further research of omadacycline, including clinical trials, for the treatment of RGM infections, especially M. abscessus.

Automated summary

This study evaluated the in vitro potency of the new tetracycline derivative omadacycline against NTM, showing high activity against most RGM species. MIC testing against RGM revealed over 90% resistance to tetracycline in the isolates tested.