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Τρίτη 8 Δεκεμβρίου 2020

Omadacycline against Nontuberculous Mycobacteria

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Nontuberculous mycobacteria (NTM) infections are increasing globally. Mycobacterium avium complex (MAC) and M. 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 aga inst 70 isolates of rapidly growing mycobacteria (RGM) of which >90% were tetracycline resistant. These included M. abscessus subsp. abscessus (20), M. abscessus subsp. massiliense (3), M. chelonae (15), M. immunogenum (7), the M. fortuitum group including six doxycycline resistant isolates (12), and the M. mucogenicum group including four doxycycline resistant isolates (10). Forty-one isolates of slowly growing mycobacteria (SGM) species including 16 isolates of MAC were also tested. Omadacycline was active against all RGM species with an MIC50 range of 0.004-0.25 and 0.06-1 μg/ml for 80% and 100% inhibition, respectively. For M. abscessus subsp. abscessus, MIC50 values were 0.06 and 0.12 μg/ml with 80% and 100% inhibition respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs for tigecycline exhibited no trailing and were generally within 1-2 dilu tions of the 100% inhibition omadacycline MIC values. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range 8->16 μg/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.

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