Management of nontuberculous mycobacterial Pulmonary disease refractory to guideline-based therapy: A systematic review

Introduction: Managing patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) unresponsive to guideline-based therapy remains challenging due to limited treatment options and complex disease progression. This study systematically reviewed existing literature on management strategies and emerging therapeutic approaches for refractory NTM-PD. Methods: We systematically reviewed studies on NTM-PD treatment failure published from inception until 31 January 2024, examining associated factors, intensification strategies, and supportive measures. Twenty-five studies met the inclusion criteria, mostly retrospective and observational, focusing on pulmonary disease by Mycobacterium avium complex and Mycobacterium abscessus species. Findings were synthesised qualitatively because of substancial heterogeneity in study design and outcomes. Results: Before treatment intensification or de-escalation, the impact of antibiotics on health-related quality of life and microbiological factors, including acquired resistance and pathogen shifts, should be assessed. Severe baseline radiological findings and multiple prior regimen modifications were associated with lower treatment success. Evidence for supportive interventions-such as nutritional counselling, respiratory rehabilitation, and psychosocial support-remains limited. Intermittent intravenous antibiotics may aid symptom control. Depending on NTM species, additional antibiotics have been explored to intensify treatment, though evidence is largely observational. Surgical resection may be considered for localised disease, but recurrence risk remains substantial, particularly with preoperative positive cultures. Novel therapeutic approaches remain under investigation as potential alternatives. Discussion: This systematic review underscores the complexity of managing refractory NTM-PD, highlighting the role of treatment intensification, symptom control, supportive measures, and knowledge gaps. While no standardised approach exists, individualised strategies incorporating clinical, microbiological, and radiological factors remain essential for optimising patient outcomes.