Rational Choice of Antibiotics and Media for Mycobacterium avium Complex Drug Susceptibility Testing.

Alexandra Aubry,Florence Morel,Jérôme Robert,Wladimir Sougakoff,Thomas Maitre,Florence Brossier,Nicolas Veziris,The Cnr-Myrma (Centre National De Référence Des Mycobactéries Et De La Résistance Des Mycobactéries Aux Antituberculeux) ,Jérémy Jaffré

doi:10.3389/fmicb.2020.00081

Abstract

The Clinical and Laboratory Standards Institute recommends the use of Mueller Hinton (MH) medium to perform drug susceptibility testing (DST) of Mycobacterium avium complex (MAC) using the microdilution method. For MAC, there has been no study on the impact of media on the determination of minimum inhibitory concentrations (MICs) of antibiotics other than clarithromycin. This study aimed at determining the impact of two media used for DST of MAC and at augmenting the number of pertinent MICs for MAC species encountered in clinical practice. MICs of antibiotics used for the treatment of MAC infections were determined for 158 clinical MAC isolates (80 M. avium, 40 M. intracellulare, 35 M. chimaera, two M. yongonense and one M. timonense) in MH and 7H9 broths using the SLOMYCO SensititreTM system (TREK Diagnostic Systems, East Grinstead, United Kingdom). The modal MICs determined in both media were the same for linezolid, moxifloxacin, rifabutin and amikacin but not for clarithromycin, rifampin and ethambutol. The kappa test for MICs converted to susceptibility categories showed an excellent agreement for clarithromycin, a moderate agreement for linezolid and a weak agreement for moxifloxacin and amikacin. For amikacin, 7H9 allowed a better distinction (fewer intermediate strains) of wild-type populations than MH. Existing breakpoints for linezolid and moxifloxacin are spread through the distribution of MICs for wild-type populations. The only breakpoints that can be used rationally are those for amikacin and clarithromycin. For amikacin, 7H9 performs better than MH, whereas both media perform equally for clarithromycin. Given that testing in 7H9, as opposed to MH, allows easier MIC measurements and yields greater reproducibility, we propose the use of 7H9 medium for DST of MAC.

Highlights

Nontuberculous mycobacteria (NTM) are ubiquitous microorganisms isolated mainly from water and soil
These strains were collected from 141 patients. 14 patients had between two and four strains included in the study, with a mean interval between two strains of 6.5 months
They were isolated from 141 patients, 96 (68%) who had a history of long-term macrolide treatment, 20 (14%) who had no history of treatment, and 25 (18%) whose history of treatment was unknown

Summary

Introduction

Nontuberculous mycobacteria (NTM) are ubiquitous microorganisms isolated mainly from water and soil. The incidence of MAC infections is increasing in most industrialized countries, possibly because of the increase in immunocompromised and/or older patients (Griffith et al, 2007; Prevots et al, 2010). These infections require antibiotic therapy based on macrolides (azithromycin or clarithromycin) combined with a rifamycin (rifampin or rifabutin) and ethambutol. Clofazimine, moxifloxacin, linezolid and bedaquiline are alternative drugs proposed mainly for the treatment of infections caused by macrolide-resistant MAC, but clinical evidence of their efficacy is lacking (Griffith et al, 2007; Koh et al, 2013; Jo et al, 2014; Philley et al, 2015)

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