Mycobacterium tuberculosis and Mycobacterium avium Complex Cutaneous Co-Infection: Diagnostic and Therapeutic Challenges

Cutaneous co-infection with Mycobacterium tuberculosis (MTB) and Mycobacterium avium complex (MAC) is extremely rare and easily missed due to overlapping histopathological features. We report a previously healthy, HIV-negative middle-aged woman who presented with a progressive destructive mass in the left inguinal-perineal region. Imaging revealed sinus tract formation, osteolytic bone lesions, and chronic inflammation in the right middle lobe of the lung. Initial metagenomic next-generation sequencing (mNGS) detected 3756 reads of the Mycobacterium tuberculosis complex (MTBC) and 111 reads of Mycobacterium intracellulare (M. intracellulare); the latter was interpreted as possible colonization or contamination because of its low abundance. Empirical anti-tuberculosis therapy produced only transient partial improvement, followed by paradoxical worsening, local recurrence, and new bone destruction. After a high suspicion of mixed infection, a MAC-directed combination regimen (including azithromycin and a short course of amikacin) was added, leading to complete clinical cure; subsequent repeat cultures confirmed the presence of MAC. This is the first report of cutaneous MTB-MAC co-infection in the inguinal-perineal region of an adult without overt immune abnormalities, accompanied by disseminated bone lesions. This case highlights that in regions where nontuberculous mycobacteria (NTM) are co-endemic, atypical destructive skin lesions with paradoxical worsening despite initial response to anti-tuberculosis therapy should raise suspicion of MAC co-infection. The combination of mNGS and conventional culture facilitates identification of mixed infections and guides precision therapy, but mNGS results must be interpreted cautiously in the clinical context.