The aetiology and epidemiology of nontuberculous mycobacteria (NTM) in Australians with cystic fibrosis

Abstract

Background: Nontuberculousmycobacterial (NTM) infections have rapidly emerged in people with CF (pwCF), threatening survival. Here, we aim to understand the epidemiology and association with NTM infection in pwCF in Australia through a national NTM surveillance study. Methods: 18 CF centres prospectively collected respiratory samples for NTM culture (Baseline, 6 months, 1 year, then annual to 4 years) (2016–2021); clinical, microbiological, geographic and social data were supplied by the clinic along with linkage data from the Australian CF Data Registry. Data for climatic and environmental variables were obtained from publicly accessible sources. Bayesian geostatistical modelling, incorporating environmental/ climatic variables along with spatial random effects, was applied to generate predictive maps identifying high-risk areas for NTM in CF patients in Australia. Unadjusted analyses are presented. Results: Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mabs) had similar prevalence (∼8%) with Mabs more likely to progress to pulmonary disease than MAC (37.8% and 12.3%, respectively (p < 0.01)). Univariate analysis showed the odds of isolating Mabs is 2–5 times higher in participants < 25 years compared to participants >25 years (Table 1). The odds of isolating a pathogenic NTM species was negatively associated with chronic Pseudomonas aeruginosa infection (Mabs Odds Ratio (OR): 0.4 (95% CI 0.2, 0.7); MAC OR 0.6 (95% CI 0.4, 0.9)) and macrolide prescription (Mabs OR: 0.5 (95% CI 0.3, 0.8); MAC OR: 0.8 (0.5–1.2)). Environmental factors associated with the occurrence of MAC include increasing odds with the proportion of cropland cover (OR 7.6 (95% Credible Interval (CrI) 1.7, 32.9)) and reduced odds with increasing bareland cover (OR 0.012 (95% CrI: 0.002, 0.560)). Mabs was positively associated with the proportion of grassland cover (OR 3.3; 95% CrI: 1.1, 9.5), while higher elevation was negatively associated with the occurrence of Mabs (OR 0.98; 95% CrI: 0.96, 0.99). Conclusions: Mabs and MAC infection in pwCF are prevalent. Isolation of these pathogenic species of NTM was negatively associated with macrolide use and the presence of chronic P. aeruginosa infection and positively associated with younger age groups. Geospatial analysis showed different associations with environmental factors depending on NTM species, with Mabs associated with grassland regions and MAC associated with cropland cover regions. Acknowledgements: Grant Support: NHMRC (APP1102494) and USA CFF (BELL19A0). Named authors: on behalf of the NTM in CF Study Investigators.