Mycobacterial Genotypes Are Associated With Clinical Manifestation and Progression of Lung Disease Caused by Mycobacterium abscessus and Mycobacterium massiliense

Abstract

Background. Mycobacterium abscessus and Mycobacterium massiliense, which cause lung disease, are variable in their clinical manifestation and progression. We hypothesized that mycobacterial genotypes represent their pathogenic phenotypes, which would result in particular genotypes being associated with disease progression. Methods. Variable number tandem repeat (VNTR) loci were selected to establish a genotype assay that was capable of differentiating patients with heterogeneous prognoses in the development cohort (48 isolates). The analysis was reevaluated in the validation cohort (63 isolates). Results. A total of 53 M. abscessus and 58 M. massiliense isolates were assembled into 3 clusters based on their VNTR genotyping. The patients in cluster A were more likely to have stable disease of the nodular bronchiectatic form; 100% of M. abscessus patients and 96% of M. massiliense patients were followed without antibiotic treatment for >24 months after diagnosis. In contrast, the patients in cluster B were more likely to have progressive disease of the nodular bronchiectatic form; 96% of M. abscessus patients and 81% of M. massiliense patients started antibiotic treatment within 24 months after diagnosis. All patients in cluster C had fibrocavitary disease and started antibiotic treatment immediately after diagnosis. The genetic distance of each clinical isolate from the reference strain was associated with the highest likelihood of disease progression and a disease phenotype of the fibrocavitary form (P <.001). Conclusions. Mycobacterial genotyping of M. abscessus and M. massiliense may provide valuable information for predicting disease phenotype and progression.