Respiratory physicians are highlighting the urgent need for large-scale trials evaluating strategies for the management of nontuberculous mycobacteria (NTM) infection in children with cystic fibrosis (CF).
The call came with new UK research showing that diagnosis and treatment of NTM infection remain challenging with no guarantee of success, particularly for Mycobacterium abscessus complex (MABS), which is linked with a more rapid decline in lung function compared with other pathogens.
The research team investigated current approaches to diagnosis, management and consequences of NTM treatment in a multicentre cohort of children with CF in the UK. They looked at data from 11 CF specialist centres from 70 patients less than 17 years old, treated for NTM infection between 2006 and 2017.
The retrospective analysis, published in Archives of Disease in Childhood, revealed that older age and previous diagnosis of allergic bronchopulmonary aspergillosis were all significantly associated with NTM infection in the patient cohort.
The symptoms most likely to be reported when NTM was first detected were increased cough (66%), increased sputum (39%), breathlessness (20%) and systemic symptoms (predominantly weight loss, 16%).
Importantly, 20% of patients were reported to be asymptomatic, which, coupled with the fact that lung function was also found to be significantly lower at diagnosis, “highlight the potential importance of early detection of NTM using proactive screening,” the researchers noted.
With regard to diagnosis, in 56% of patients NTM was detected as part of screening when asymptomatic, in 27% following respiratory symptoms and in 17% as part of routine screening of patients who had respiratory symptoms.
Following diagnosis, there was a wide variance in treatment choice, but treatment to eradicate NTM was “intensive and lengthy” and was commonly linked with side effects. The vast majority (90%) of patients with M. avium complex (MAC) infection were treated as per guidelines, but only around half of those with MABSC were given guideline-directed induction and two-thirds maintenance treatment.
With regard to outcomes, MAC eradication rates were “relatively high”, at 80%, whereas MABSC eradication occurred in only 48% of patients. However, the researchers highlighted that children in the studied cohort were treated over a long period of time, since 2006, and for the majority this was before publication of guidelines by the CF Foundation and European CF Society in 2016 and by the British Thoracic Society in 2017.
“Clinical practice has changed and evolved during the course of time and a single-centre paediatric study has reported a higher rate of MABSC eradication of 65%-73% between 2011 and 2018,” they said.
Commenting on the findings, Consultant Chest physician Dr Dennis Wat, from Liverpool Heart and Chest Hospital, said NTM infections in children with CF, which have doubled between 2010 and 2015, “pose significant challenges for clinical management”.
“The clinical management of children with CF who isolate NTM represents an area of evolving expertise and practice,” he told the limbic, and highlighted that the recent (non-CF specific guidelines) published by the American Thoracic Society in 2020, “do not encompass management of NTM in children, [which] is in part due to a paucity of clinical evidence in this cohort”.
“This large retrospective multicentre study of children with CF treated for NTM infection published by Saint et al highlights clinical challenges and areas of uncertainty that exist throughout all phases of managing pulmonary NTM infections in children with CF, along with variations in practice and antibiotic regime due to intolerances,” he said, and emphasised “the unmet need for urgent research to facilitate the development of paediatric-specific protocols”.