In Vitro Susceptibility Testing of Eravacycline against Nontuberculous Mycobacteria

Abstract

Nontuberculous mycobacteria (NTM) infections are increasing worldwide. Mycobacterium avium complex (MAC) and the M. abscessus species are the most commonly cultured NTM and treatment options are limited, especially for the M. abscessus species. In this study, the in vitro activity of eravacycline, a new tetracycline derivative, was tested against 110 clinical isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 60 isolates of rapidly growing mycobacteria (RGM), of which ~70% were tetracycline resistant. These included M. abscessus subsp. abscessus (8 isolates), M. abscessus subsp. massiliense (5), M. chelonae (10), M. immunogenum (3), M. fortuitum group (20) including 12 doxycycline-resistant isolates, and M. mucogenicum group (10) including three doxycycline-resistant isolates. Due to trailing, eravacycline MICs were read at 80% and 100% inhibition. Eravacycline was active against all RGM species, with MIC₅₀ ranges of ≤0.015 to 0.5 and ≤0.015 to 0.12 μg/mL for 100% and 80% inhibition, respectively. For M. abscessus subsp. abscessus, MIC₅₀ values were 0.12 and 0.03 μg/mL with 100% and 80% inhibition, respectively. MICs for tigecycline were generally within 1 to 2 dilutions of the 100%-inhibition eravacycline MIC values. Fifty isolates of slowly growing mycobacteria (SGM) species, including 16 isolates of MAC, were also tested. While there was no trailing observed in most SGM, the eravacycline MICs were higher (MIC range of >8 μg/mL), except for M. kansasii and M. marinum which had MIC₅₀ values of 1 μg/mL. This study supports further evaluation of eravacycline, including clinical trials for the development of RGM treatment regimens, especially for M. abscessus.

Keywords: eravacycline; nontuberculous mycobacteria; susceptibility.

FIG 1

Eravacycline MICs show a trailing pattern similar to that of omadacycline, which is shown in this graphic representation. The wells in which 80% and 100% inhibition were read are indicated with arrows. (Reproduced from previous work [22]).

FIG 2

Eravacycline MICs show a trailing pattern similar to that of omadacycline, which is shown in this photograph (no photographs of eravacycline wells were available). (Reproduced from previous work [22]).