Bedaquiline for Nontuberculous Mycobacterial Disease: Insights from the Largest National Case Series

Abstract

Introduction First-line antibiotics for disease caused by nontuberculous mycobacteria (NTM) are often poorly effective. Bedaquiline is an attractive therapeutic option. Evidence regarding its clinical efficacy is limited. We report outcomes from the largest UK case series of patients with NTM disease who received bedaquiline. Methods Clinicians in NTM centres were contacted to ascertain whether they had used bedaquiline to treat NTM disease. Inclusion criteria for cases were microbiological confirmation of NTM infection and treatment for NTM disease with bedaquiline. Retrospective chart review was undertaken to collate demographics, investigations, regimens and outcomes. Results Seventeen patients (10 female; 7 male; median age decile 45-54 years) across 11 hospitals were identified. The commonest pre-existing lung conditions were bronchiectasis (n=5, 29%) and cystic fibrosis (n=4, 24%). Four individuals (24%) had HIV infection; three of whom had AIDS. Nine (53%) had NTM pulmonary disease, three (18%) single-site extrapulmonary disease and five (29%) disseminated disease. NTM disease occurred most frequently secondary to Mycobacterium abscessus (MAB) (n=8, 47%) and Mycobacterium avium complex (MAC) (n=6, 35%). The commonest indication for bedaquiline was NTM treatment failure (n=13, 76%). The BTS MDR TB CAS recommended bedaquiline in seven cases. Bedaquiline was started a median 18.0 (interquartile range (IQR) 4.3-25.5) months after NTM treatment initiation. Median bedaquiline treatment duration was 7.5 (IQR 5.6-12.0) months. Symptoms completely resolved in five (29%) cases, partially resolved in six (35%) and did not change in two (12%). Complete radiological resolution was observed in three (18%), partial resolution in four (24%) and no radiological change in five (29%). Persistent culture conversion was achieved in four (24%) individuals (three MAC, one MAB). Four (24%) individuals (three MAB, one MAC) failed to culture convert. Adverse events associated with bedaquiline included QTc interval prolongation (n=4, 24%), hepatotoxicity (n=3, 18%) and nausea (n=2, 12%). Four individuals (24%) had no bedaquiline- related side effects. Three deaths that occurred while taking bedaquiline were not attributed to the drug by the treating clinicians. Conclusions Adding bedaquiline to NTM treatment regimens is associated with variable treatment outcomes. Prospective clinical studies evaluating the efficacy of bedaquiline in this context appear warranted.