From anonymity to stardom: history of nontuberculous mycobacterial disease in humans

Until recently, nontuberculous mycobacteria (NTM) were not considered as human pathogens. Their nomenclature has evolved over several years, until 1971 when finally named as NTM, which is universally accepted now. Because of continuously evolving diagnostic methods, several new species/subspecies of NTM were identified. Presently, nearly 200 NTM species have been reported. Similar to tuberculosis (TB), NTM are known to involve both pulmonary and extrapulmonary organs. Diagnosis of NTM disease is quite cumbersome and is primarily based on their growth characteristics on solid and liquid cultures. Biochemical testing was the mainstay of NTM diagnosis and species identification in the past, which was often erroneous. Recently, molecular tests like line probe assay, targeted, and whole genome sequencing have become available for rapid and accurate diagnosis. Isolation and identification of NTM species/subspecies alone do not warrant treatment. After ascertaining clinical relevance, virulence of NTM species, and evidence for clinical and radiological progression, the decision to administer treatment is taken. Multiple drugs are often administered for 12 months after sputum culture conversion, except in <i>M. kansasii</i>, and <i>M. szulgai</i>, where this constitutes the total treatment duration, with careful follow‑up for relapse and exogenous new infection. The present review traces the history, evolution of classification of NTM, strides made in the diagnosis and treatment of NTM disease. By integrating these historical lessons on taxonomy, culture phenotypes, genotypes and diagnostic pitfalls with contemporary molecular tools and species/subspecies specific treatment regimens, current practice enables more precise, timely, and patient-centered management of NTM disease.