Drug susceptibility of Mycobacterium avium isolated from patients with mycobacteriosis with positive and negative HIV status | CMAC

Drug susceptibility of Mycobacterium avium isolated from patients with mycobacteriosis with positive and negative HIV status

Clinical Microbiology and Antimicrobial Chemotherapy. 2025; 27(2):206-216

Type
Original Article

Objective.

Comparative assessment of in vitro susceptibility of M. avium isolated from patients with mycobacteriosis (MB) with positive and negative HIV status.

Materials and Methods.

M. avium isolates of were revealed during 2018–2023 from clinical samples of 402 adult patients (≥ 18 years old) in the National Medical Research Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation: 144 strains were isolated from individuals with HIV infection (HIV+) and 258 – from patients with a negative HIV status (HIV-). Susceptibility was determined for 15 antimicrobials: amikacin, clarithromycin, rifabutin, rifampin, ethambutol, streptomycin, ciprofloxacin, doxycycline, isoniazid, ethionamide, linezolid, moxifloxacin, trimethoprim-sulfamethoxazole, bedaquiline, reviewed using the broth microdilution method in accordance with the CLSI M24-A2, 2018 guidelines. Antimicrobial susceptibility categories were determined based on minimum inhibitory concentration (MIC) breakpoints according to CLSI M24S, 2023 standards. For amikacin, clarithromycin, linezolid, and moxifloxacin, M. avium complex breakpoints were used. For ciprofloxacin, doxycycline, rifabutin, and rifampin, MIC breakpoints for other slow-growing NTMs (M. kansasii and M. marinum) according to CLSI M24S, 2023 Non-Species Breakpoints were used. For ethambutol, isoniazid, streptomycin, ethionamide, bedaquiline, delamanid, MIC breakpoints for slowgrowing NTM have not been established. Quality control is performed using M. avium strain ATCC 700898.

Results.

The highest susceptibility level (> 60%) of M. avium in patients with MB HIV+ and MB HIV- was observed to rifabutin (94.4% and 87.6%), amikacin (78.5% and 72.1%), clarithromycin (75.7% and 64.7%); relatively low susceptibility level (60–40%) – to moxifloxacin (56.9% and 50.4%), trimethoprimsulfamethoxazole (43.6% and 52.9%); the lowest susceptibility level (< 40%) – to doxycycline (2.1% and 0.4%), linezolid (14.6% and 14.7%), ciprofloxacin (14.6% and 15.5%), rifampicin (34.0% and 36.4%). Statistically significant higher susceptibility was noted for the isolates from patients with MB HIV+ than in patients with MB HIV- to: rifabutin (94.4% versus 87.6%, p = 0.04), clarithromycin (72.1% vs. 64.7%, p = 0.03). There were more resistant isolates in patients with MB HIV- than in MB HIV+ to: rifabutin (12.4% vs. 5.6%, p = 0.04), clarithromycin (19.8% vs. 9.7%, p = 0.01), moxifloxacin (29.1% vs. 18.8%, p = 0.03). More isolates with intermediate susceptibility to amikacin were detected in the group of patients with MB HIV- than with MB HIV+ (6.3% vs. 18.6%, p = 0.001). In addition, higher MIC50 values were observed for M. avium isolates from HIV- MB patients than from HIV+ MB for: amikacin (16 μg/mL vs. 8 μg/mL), clarithromycin (8 μg/mL vs. 4 μg/mL), isoniazid (16 μg/mL vs. 8 μg/mL), streptomycin (32 μg/ mL vs. 16 μg/mL). Higher MIC90 values were also observed against M. avium isolates from MB HIV- than MB HIV+ patients for: rifabutin (4 μg/ml vs. 2 μg/ml), amikacin (32 μg/ml vs. 16 μg/ml), clarithromycin (32 μg/ml vs. 16 μg/ml), moxifloxacin (8 μg/ml vs. 4 μg/ml), doxycycline (256 μg/ml vs. 128 μg/ml), rifampin (32 μg/ml vs. 16 μg/ml), delamanid (2 μg/ml vs. 1 μg/ml), isoniazid (128 μg/ml vs. 32 μg/ml), streptomycin (128 μg/ml vs. 64 μg/ml).

Conclusions.

The level of in vitro activity of 9 of 15 antimicrobials (clarithromycin, rifampicin, rifabutin, amikacin, streptomycin, moxifloxacin, doxycycline, isoniazid, delamanid) was lower for M. avium isolates from MB HIV- patients than for isolates from MB HIV+ patients. These results were confirmed by statistically significant differences in the number of susceptible, moderately susceptible and resistant isolates and/or MIC50 and/or MIC90 values, which were higher in the MB HIV- group than in the MB HIV+ group. At the same time, the level of activity of none of the 15 studied antimicrobials against M. avium isolates from MB HIV+ patients was lower than those from MB HIV- patients.

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