Antimicrobial susceptibility of Mycobacterium avium complex mycobacteria isolated from patients in Ural Federal District of the Russian Federation

Abstract

Objective. To assess minimal inhibitory concentrations (MICs) of antimicrobials for Mycobacterium avium complex (MAC) mycobacteria isolated from patients in Ural Federal District of the Russian Federation. Materials and Methods. We determined MICs for 33 M. avium and 34 M. intracellulare strains isolated from 67 patients with mycobacteriosis or tuberculosis/mycobacteriosis co-infection during 2018– 2019. SLOMYCO Sensititre test-system was used for susceptibility testing to 12 antibiotics: amikacin, streptomycin, clarithromycin, ethambutol, rifabutin, rifampicin, ciprofloxacin, ethionamide, isoniazid, linezolid, moxifloxacin, and doxycycline. Mycobacteria isolates were categorized according to their MICs as “susceptible”, “susceptible with increased exposure to the drug”, and “resistant” using CLSI breakpoints (2018). Breakpoints for amikacin, clarithromycin, linezolid and moxifloxacin were available for M. avium complex, for ciprofloxacin, doxycycline, rifabutin, rifampicin – for slow growing nontuberculous mycobacteria other than MAC mycobacteria. Breakpoints for ethambutol, isoniazid, streptomycin and ethionamide were not available. Results. Rates of susceptibility of M. avium and M. intracellulare were: amikacin – 96.9% and 97.0%, clarithromycin – 84.8% and 97.1%, linezolid – 9.1% and 23.5%, moxifloxacin – 57.6% and 38.2%, respectively. Majority of M. avium and M. intracellulare isolates were resistant to ciprofloxacin, doxycycline, and rifampicin. Ethambutol MICs for 84.4% of M. avium and for 67.7% of M. intracellulare isolates were > 8 mg/L. The majority of studied isolates (64.2%) were susceptible to at least three antimicrobials for the treatment of infections caused by MAC mycobacteria. Conclusions. Macrolides and aminoglycosides were the most effective against MAC mycobacteria in our study. Use of macrolides in combination with rifabutin and amikacin or moxifloxacin and amikacin may increase treatment efficacy in infections caused by M. avium and M. intracellulare.

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

“…However, in the case of M. intracellulare , the same considerations about the same study by Cho, 2018 [ 37 ] are probably no longer applicable, because the number of strains with MIC ≥ 32 mg/L is too high and two subpopulations of strains possessing different MICs in vitro can be assumed. Furthermore, the bimodal distribution was also found in Umpeleva, 2022 [ 30 ], Litvinov, 2018 [ 20 ], and Zhao, 2014 [ 39 ]. Most studies show the first mode of distribution at 4 mg/L, which is slightly lower compared to M. avium .…”

“…For two studies [ 30 , 34 ], the strains with the two highest MIC values were combined into one category, which was due to the technical aspect of the processing of the results. The MIC distributions of the isolates given below are presented on a synthetic scale: the distributions were normalized to values between 1 and 4, proportional to the maximum value in the distribution.…”

“…Most M. avium strains had MICs ≤ 0.25 mg/L ( n = 378, 59%). One study for 33 strains [ 30 ] had a distinct distribution, with 23 strains having MIC ≥ 8 mg/L. For M. intracellulare strains rifabutin MIC distributions are shifted to higher values, strains with a minimally detectable MIC ≤ 0.25 mg/L accounting for 31% ( n = 113 of 370) ( Table S5 ).…”