Non-antibiotic treatment for nontuberculous mycobacteria lung infection in people with cystic fibrosis – A systematic review

Nontuberculous mycobacteria (NTM) cause pulmonary disease in people with cystic fibrosis (pwCF). Recommended prolonged antibiotic therapy has significant toxicity. Non-antibiotic therapies for NTM pulmonary disease and supporting evidence were identified. Online databases and trials registries were searched for randomised or non-randomised studies (NRSIs). Primary outcomes were microbiology, quality of life (QoL), adverse events, lung function and pulmonary exacerbations. Bias was assessed using the relevant Joanna Briggs Institute tool. Seven NRSIs assessed: phage therapy, CF transmembrane conductance regulator (CFTR) modulator therapy (ETI: elexacaftor/tezacaftor/ivacaftor), inhaled nitric oxide (INO) and surgical lung resection. All had varying response definitions and very low-certainty evidence. The phage therapy study reported NTM culture conversion (n=4), partial conversion (n=4), inconclusive response (n=4) or no response (n=4). In one study of ETI with antibiotics (n=7) or without (n=8), nine participants eradicated NTM after a year, with positive cultures decreasing during treatment compared to pre-treatment. In another study (n=91) NTM infection fell by approximately 75% after at least two months of ETI (no information on concomitant treatment). In three INO studies (n=16), NTM was eradicated (n=2), showed transient negative cultures (n=6) and reductions in bacterial burden (n=11). Comparing lung resection (n=3) to antibiotic therapy (n=6), all surgical patients cleared M abscessus remaining negative at 24 months; 4 patients taking antibiotics cleared NTM. All M avium complex (MAC)-positive patients (surgery, n=1; antibiotic, n=2) cleared infection. Currently, non-antibiotic therapies are considered case by case. Randomised studies are needed to increase evidence quality and inform clinical practice for interventions appearing safe and feasible in pilot studies.