Consensus on the management of refractory nontuberculous mycobacterial pulmonary disease

BACKGROUND: Nontuberculous mycobacteria (NTM) are associated with chronic and challenging infections, particularly pulmonary disease (NTM-PD). While clinical guidelines provide treatment recommendations for the most common disease-causing species, they offer limited guidance on managing treatment failures. This study aims to develop a consensus-based decision-making framework for addressing treatment failure in NTM-PD. METHODS: A panel of 16 international experts used the e-Delphi method to address gaps in NTM-PD management. Initial statements were derived from an open-ended questionnaire, supported by a prior systematic review. Iterative rounds of expert evaluation were conducted until a consensus was reached on treatment failure definitions, decision-making criteria, therapeutic strategies and supportive care measures. RESULTS: Consensus defined treatment failure as the absence of culture conversion after 6 months of appropriate antimycobacterial therapy, while clinical and radiological deterioration were considered additional but non-mandatory criteria. Treatment intensification or de-escalation decisions were based on patient preferences, clinical status, comorbidities, disease severity, antibiotic tolerance, resistance patterns and previous treatment history. Treatment intensification highlighted the necessity for personalised multidrug antibiotic regimens. De-escalation strategies focus on delivering optimal, patient-centred supportive care while minimising pharmacological adverse effects, by opting for simplified antibiotic regimens, intermittent antibiotic courses for symptomatic control or the cessation of antimicrobial therapy. CONCLUSION: This study offers a structured approach to managing treatment failure in NTM-PD, addressing patient selection, treatment intensification, de-escalation and supportive care, while championing individualised strategies. Future research should concentrate on validating predictive factors for treatment response, refining therapeutic regimens and investigating host-directed therapies to enhance patient outcomes.