Detection of Nontuberculous Mycobacterial Skin Infection by Next-Generation Sequencing: A Pilot Study

Background: Nontuberculous mycobacteria (NTM) skin infections pose significant diagnostic challenges in clinical practice, due to nonspecific clinical/histopathological features and limitations of conventional pathogenic detection methods. Metagenomic next-generation sequencing (mNGS) offers a promising approach but requires further evaluation. Methods: A prospective pilot study at Peking Union Medical College Hospital enrolled 20 patients with cutaneous NTM infection, confirmed by positive skin culture or mNGS. All patients underwent thorough clinical assessment, skin biopsy for histopathology and culture, and mNGS testing of skin tissue. Treatment was based on identified species and disease extent. Treatment outcomes were tracked. Results: Among 20 patients (median age 45.5 years), fingers were the most common site affected (n = 10), followed by forearms (n = 7), hands (n = 4), and face (n = 4). Mycobacterium marinum was the predominant pathogen (n = 12), associated with fish bone puncture, followed by M. abscessus (n = 4). mNGS demonstrated a substantially higher positivity rate than culture (95% [19/20] vs. 30% [6/20]) and delivered results faster. Histopathology revealed granulomatous inflammation in all cases. Nineteen patients presented with non-disseminated disease; one immunocompromised patient (GATA2 deficiency) had disseminated M. abscessus infection. Treatment success was achieved in 17 patients (85%) with tailored antibiotic regimens. Adverse drug effects occurred in seven patients. Conclusions: In this pilot study of cutaneous NTM infections, mNGS enabled more rapid diagnosis relative to conventional culture. Clinical presentation and exposure history correlate with specific NTM species. Integrating mNGS with clinical assessment significantly improves diagnosis and management.