In vitro assessment of 17 antimicrobial agents against clinical Mycobacterium avium complex isolates

Abstract

Background Recently, Mycobacterium avium complex (MAC) infections have been increasing, especially in immunocompromised and older adults. The rapid increase has triggered a global health concern due to limited therapeutic strategies and adverse effects caused by long-term medication. To provide more evidence for the treatment of MAC, we studied the in vitro inhibitory activities of 17 antimicrobial agents against clinical MAC isolates. Results A total of 111 clinical MAC isolates were enrolled in the study and they were identified as M. intracellulare, M. avium, M. marseillense, M. colombiense, M. yongonense, and two isolates could not be identified at the species level. MAC strains had relatively low (0–21.6%) resistance to clarithromycin, amikacin, bedaquiline, rifabutin, streptomycin, and clofazimine, and the resistant rates to isoniazid, rifampin, linezolid, doxycycline, and ethionamide were very high (72.1–100%). In addition, M. avium had a significantly higher resistance rate than that of M. intracellulare for ethambutol (92.3% vs 40.7%, P < 0.001), amikacin (15.4% vs 1.2%, P = 0.049), and cycloserine (69.2% vs 25.9%, P = 0.004). Conclusions Our results supported the current usage of macrolides, rifabutin, and aminoglycosides in the regimens for MAC infection, and also demonstrated the low resistance rate against new drugs, such as clofazimine, tedizolid, and bedaquiline, suggesting the possible implementation of these drugs in MAC treatment.

Differences in Drug-Susceptibility Patterns between Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium chimaera Clinical Isolates: Prospective 8.5-Year Analysis by Three Laboratories

“…Regarding the drug susceptibility pattern, several studies published in recent years have compared the pattern of antibiotic resistance between M. avium and M. intracellulare [14][15][16][19][20][21][22]. A recent study by Maurer et al [22] included isolates of four MAC species (M. avium, M. intracellulare, M. chimaera, and M. colombiense), concluding that there were no significant differences among these species.…”

“…Several reports suggest that M. chimaera is less virulent than the other two species [11,12]; however, data on the specific distribution and frequency of M. chimaera are scarce since most of the published epidemiological studies did not differentiate M. chimaera from M. intracellulare. Several publications have suggested that there is a differential drug susceptibility pattern between M. avium and M. intracellulare [13][14][15][16]. Therefore, these discrepancies are not clearly established and current guidelines [5,6] do not differentiate the treatment recommendations between these species.…”

Recognizing Non-vertebral Manifestation of Mycobacterium avium Complex Osteomyelitis in a Patient With HIV

“…Azithromycin or clarithromycin are commonly used agents from the macrolide class [1]. Monotherapy with a single antimicrobial agent is avoided to decrease the risk of drug resistance, and susceptibility testing should be done on all isolates [8]. The duration of treatment is at least 12 months due to difficulty in its eradication [1].…”

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

“…The analysis of the MIC distribution of M. avium isolates for most of the studies performed using SLOMYCO plates converged well ( Figure 7 , Table S9 ), with maximums located at 16–32 mg/L, except for one study with a small number ( n = 13) of isolates [ 28 ]. A study of 1006 Cho strains performed according to CLSI standards yields a broader distribution.…”

“…For MAC isolates, CLSI recommends two breakpoint moxifloxacin concentrations of 1 and 2 mg/L [ 24 ]; strains with MIC = 2 mg/L are classified as intermediately resistant. Only studies by Lin, 2022 [ 28 ] and Ying, 2022 [ 29 ] with bimodal MIC distributions meet these criteria, but the number of strains tested is small. An attempt to detect mutations in the gyrA and gyrB genes in strains presumably resistant to moxifloxacin using CLSI criteria was unsuccessful [ 72 ].…”