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Publications

Journal Article Systematic Review Review Ppublish

PubMed: 41733158 DOI: 10.1080/25310429.2026.2632467

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

Pulmonology 32(1):2632467

Authors: Diana Moreira-Sousa, Beatriz Martins, Ana Aguiar, Marina Pinheiro, Onno W Akkerman, Timothy R Aksamit, Stefano Aliberti, Claire Andrejak, Charles L Daley, Jakko van Ingen, Christoph Lange, Marc Lipman, Michael R Loebinger, Mateja Jankovic Makek, Kozo Morimoto, Rachel Thomson, Dirk Wagner, Kevin L Winthrop, Jae-Joon Yim, Raquel Duarte

Affiliations

  • Pulmonology Department, Local Health Unit Cova da Beira, Covilhã, Portugal.
  • Pulmonology Department, Local Health Unit São João, Porto, Portugal.
  • EPIUnit ITR, Instituto de Saúde Pública da Universidade do Porto, Universidade do Porto, Porto, Portugal.
  • Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
  • Public Health Unit, Local Health Unit Barcelos/Esposende, Barcelos, Portugal.
  • Department of Pulmonary Disease and Tuberculosis, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
  • Tuberculosis Centre Beatrixoord, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands.
  • Mayo Clinic, Pulmonary Disease and Critical Care Medicine, Rochester, MN, USA.
  • Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • IRCCS Humanitas Research Hospital, Respiratory Unit, Milan, Italy.
  • Department of Respiratory Diseases, Amiens-Picardie University Hospital, Amiens, France.
  • UR 4294 AGIR, Picardie Jules Verne University, Amiens, France.
  • Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO, USA.
  • Division of Infectious Diseases, Department of Medicine, University of Colorado, Aurora, CO, USA.
  • Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Aurora, CO, USA.
  • Radboudumc Community for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • Division of Clinical Infectious Diseases, Research Centre Borstel, Borstel, Germany.
  • German Centre for Infection Research (DZIF), Partner Site Borstel-Hamburg-Lübeck-Riems, Borstel, Germany.
  • Respiratory Medicine and International Health, University of Lübeck, Lübeck, Germany.
  • Department of Pediatrics, Global and Immigrant Health, Global Tuberculosis Program, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
  • Respiratory Medicine, Royal Free Hospital NHS Foundation Trust, London, & University College London, London, UK.
  • Royal Brompton Hospital and NHLI, Imperial College London, London, UK.
  • Clinic for Respiratory Diseases, University Hospital Centre Zagreb, Zagreb, Croatia.
  • School of Medicine, University of Zagreb, Zagreb, Croatia.
  • Respiratory Disease Centre, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Kiyose, Japan.
  • Department of Clinical Mycobacteriosis, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
  • Division of Clinical Research, Fukujuji Hospital, Japan Anti-Tuberculosis Association, Kiyose, Japan.
  • Gallipoli Medical Research and Greenslopes Clinical Unit, The University of Queensland, Brisbane, Australia.
  • Division of Infectious Diseases, Department of Internal Medicine II, Freiburg University Medical Centre, Freiburg, Germany.
  • Department of Epidemiology, Helmholtz Centre for Infection Research Braunschweig, Brunswick, Germany.
  • Division of Infectious Diseases, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
  • Centre for Infectious Disease Studies, Oregon Health & Science University-Portland State University School of Public Health, Portland, OR, USA.
  • Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • Centro de Saúde Pública Doutor Gonçalves Ferreira - Instituto de Saúde Pública Doutor Ricardo Jorge, INSA Porto, Porto, Portugal.

Abstract

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.

MeSH

Quality Of Life, Therapeutics, Lung Diseases