Abstract:

Objective: To analyze the subspecies distribution characteristics and differences in drug resistance profiles of acid-fast bacilli (AFB) smear-negative clinical Mycobacterium abscessus complex (MABC) isolates from multiple regions in China, and to explore their clinical significances. Methods: A retrospective study was conducted on 103 patients with non-tuberculous mycobacteria (NTM) lung disease (preliminarily identified as MABC infection) admitted to tuberculosis-designated hospitals across eight provinces/autonomous regions/municipalities in China between January 1st and May 31st, 2020. Whole genome sequencing (WGS) was employed for precise subspecies identification of the isolates. The minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were determined using the broth microdilution method. Results: Among the 103 isolates preliminarily identified as MABC, 91 were confirmed as MABC by WGS. Among them, 64 (70.33%) were identified as Mycobacterium abscessus (M.ab) and 27 (29.67%) as Mycobacterium massiliense (M.mas). Among the 91 MABC-infected patients, the distribution of the two subspecies across the three age groups (<45, 45-59, ≥60 years) showed a statistically significant difference (χ²=10.144, P=0.006). Further pairwise comparisons of the proportions of the two subspecies within each age group revealed that in the middle-aged group (45-59 years), the proportion of M.ab was 10.94% (7/64), significantly lower than that of M.mas (37.04%, 10/27; χ²=8.515, P=0.004). In the elderly group (≥60 years), the proportion of M.ab was 37.50% (24/64), significantly higher than that of M.mas (14.81%, 4/27; χ²=4.587, P=0.032). Regarding clinical symptoms, the incidence of hemoptysis in patients with M.ab infection was 26.56% (17/64), significantly higher than in those with M.mas (7.41%, 2/27; χ²=4.221, P=0.040), whereas the incidence of cough in patients with M.mas was 96.30% (26/27), significantly higher than in those with M.ab (70.31%, 45/64; χ²=7.373, P=0.007). Furthermore, the resistance rate of M.ab to clarithromycin was 28.12% (18/64), which was significantly higher than that of M.mas (7.41%, 2/27; χ²=4.673, P=0.031). Conclusion: M.ab is the dominant pathogenic subspecies among MABC clinical isolates. There are significant differences between subspecies in terms of age distribution, clinical symptoms, drug resistance phenotypes, and resistance risks. Accurate identification at the subspecies level should be advocated in clinical diagnosis to enable the adoption of tailored therapeutic regimens, thereby achieving differentiated precision treatment for MABC infections.

Key words: Mycobacterium, nontuberculous, Mycobacterium abscessus, Whole genome sequencing, Microbial sensitivity tests