Contemporary challenges in the pharmacological management of nontuberculous mycobacterial disease

Introduction Pulmonary nontuberculous mycobacterial disease (NTM-PD) has overtaken tuberculosis as the most common chronic mycobacterial lung infection in several industrialized countries, including Japan. Macrolide-based multidrug regimens remain the backbone of therapy but are prolonged and toxic; only about 60% of patients achieve culture conversion, and about half of these experience recurrence after completing treatment. The drug pipeline remains sparse.Areas covered We summarize contemporary pharmacological management of NTM-PD and how longitudinal genomic monitoring might help address the challenges that limit it. PubMed/MEDLINE, Embase, the Cochrane Library and ClinicalTrials.gov were searched from 1 January 2000 to 31 July 2026, supplemented by guidelines, conference proceedings (2020–2026) and sponsor announcements. We examine three sequencing platforms developed by our group, MGIT-Seq, NALC-Seq and digital variable-number tandem repeat typing, distinguishing the microbiological information they provide from the clinical benefit of acting on it, which remains unproven.Expert opinion Genomic information can help clinicians make treatment decisions faster and more accurately. However, it cannot replace other important factors that affect patient outcomes. In addition, no prospective trial has yet shown that genome-guided management improves clinical outcomes. Future trials should include genomic biomarkers as pre-specified endpoints and compare targeted testing with routine testing for all patients.