关键词: 分枝杆菌感染, 微生物敏感性试验, 抗菌药, 药物毒性

Abstract:

Objective: To investigate the in vitro antimicrobial susceptibility profiles of clinical isolates of Mycobacterium abscessus complex (MABC), and to analyze the associations between targeted therapeutic medicine and clinical adverse drug reactions (ADR), thus providing evidence for precision clinical anti-infective therapy and pharmaceutical care. Methods: A total of 104 non-duplicate clinical MABC isolates and corresponding patient data were retrospectively collected from Fuzhou Pulmonary Hospital of Fujian Province between January 1, 2020, and December 31, 2024. Initial screening was performed using MGIT 960 system and gene chip technology, followed by subspecies identification using fluorescence PCR melting curve analysis and next-generation whole-genome sequencing. The strains were resuscitated and sub cultured in Middlebrook 7H9 medium. The in vitro susceptibilities to nine antimicrobial agents (amikacin, linezolid, clarithromycin, doxycycline, imipenem, moxifloxacin, ciprofloxacin, cefoxitin, and trimethoprim-sulfamethoxazole) were determined by the broth microdilution method. A “strain-clinical information” database was concurrently established. Fisher’s exact test was employed to analyze differences in susceptibility between subspecies, while heatmaps and Sankey diagrams were used to visually display susceptibility profiles and drug-ADR association patterns. Results: Among 103 MABC isolates (excluding one M.abscessus subsp. Bolletii isolate), the highest susceptibility rate was observed for amikacin (99.0%, 102/103), followed by linezolid (86.4%, 89/103) and clarithromycin (83.5%, 86/103). The highest resistance rate was recorded for doxycycline (64.0%, 66/103). The susceptibility rates to imipenem (12.6%, 13/103), moxifloxacin (29.1%, 30/103), and ciprofloxacin (30.1%, 31/103) were all below 31%, with notably high proportions of intermediate results (61.2%, 48.6%, and 46.6%, respectively). Both M.abscessus subsp. Abscessus (n=77) and M.abscessus subsp. Massiliense (n=26) showed high susceptibility rates to amikacin (100.0% vs. 96.2%), clarithromycin (81.8% vs. 88.5%), and linezolid (88.3% vs. 80.8%). No statistically significant differences were observed between the two subspecies for susceptibilities to the nine tested antimicrobial agents:clarithromycin (Fisher’s exact probability method, P=0.272), imipenem (Fisher’s exact probability method, P=0.378), moxifloxacin (χ²=1.870, P=0.393), linezolid (Fisher’s exact probability method, P=0.248), doxycycline (Fisher’s exact probability method, P=0.693), trimethoprim-sulfamethoxazole (Fisher’s exact probability method, P=0.155), amikacin (Fisher’s exact probability method, P=0.253), cefoxitin (Fisher’s exact probability method, P=0.086), and ciprofloxacin (χ²=1.087, P=0.581). Of the 104 patients, 78 received antimicrobial treatment among whom the overall incidence of ADRs was 51.3% (40/78). Association analyses revealed that rifabutin was significantly associated with liver dysfunction (OR=12.48, 95%CI:2.20-132.47, FDR-corrected P=0.033) and gastrointestinal reactions (OR=5.59, 95%CI:1.68-19.95, FDR-corrected P=0.033). Conclusion: This study demonstrates that amikacin, linezolid, and clarithromycin exhibit favorable in vitro inhibitory activity against MABC. In this cohort, no significant differences in the routine susceptibility distributions to the tested agents were observed between the bscessus and massiliense subspecies. In the clinical decision-making of combination therapy, in vitro susceptibility results should be integrated with ADR risk profiles, with particular attention to rifabutin-related hepatotoxicity and gastrointestinal reactions, to enhance treatment safety.

Key words: Mycobacterium infections, Microbial sensitivity tests, Anti-bacterial agents, Drug toxicity