Microbial Clearance of Refractory Mycobacterium avium Complex Pulmonary Disease During Pembrolizumab and Intensified Antimicrobial Therapy: A Case Report

<b>Background:</b> Pulmonary infections caused by <i>Mycobacterium avium</i> complex (MAC) are notoriously difficult to treat, particularly in the context of multidrug resistance. Immunotherapy with checkpoint inhibitors, though effective in various malignancies, has uncertain immunomodulatory effects on chronic infections such as MAC. <b>Case Summary:</b> We report a case of a 67-year-old man with at least a 6-year history of treatment refractory MAC who developed stage IIIB mismatch repair-deficient colon adenocarcinoma. Despite years of multidrug therapy, the patient had persistent positive acid-fast bacilli cultures. Upon initiation of pembrolizumab for colon cancer, with no concurrent anti-MAC therapy, he experienced radiologic and microbiologic improvement. Following subsequent reinitiation of multidrug MAC therapy, he achieved his first documented negative culture after over a decade of infection and has remained culture-negative and in cancer remission for over two years. <b>Conclusions:</b> This case suggests that immune checkpoint inhibitors like pembrolizumab may enhance antimicrobial immune responses against MAC through PD-1 pathway modulation. The temporal association between pembrolizumab therapy and MAC clearance warrants further investigation into immunomodulatory approaches for drug-resistant mycobacterial infections, particularly as adjunctive therapy to conventional antimicrobial regimens.