Managing antibiotic resistance in nontuberculous mycobacterial pulmonary disease: challenges and new approaches

ABSTRACT

Introduction: The incidence and prevalence rates of nontuberculous mycobacterial (NTM) pulmonary disease have been continuously increasing worldwide. However, the rate of successful treatment of this disease greatly needs improving, particularly when intrinsic (natural) drug resistance and acquired drug resistance in NTM pulmonary disease are associated with poor outcomes for patients.

Areas covered: This review covers the major pathogens that cause NTM pulmonary disease caused by Mycobacterium avium complex, Mycobacterium abscessus, and Mycobacterium kansasii; the key drugs and recommended regimens used in the treatment of NTM pulmonary disease; the factors that contribute to resistance to the key drugs, including genetic factors and monotherapy; and the treatment strategies, including revised antibiotic regimens and surgery, that can be used to treat drug-resistant NTM pulmonary disease.

Expert opinion: To avoid and overcome drug resistance in NTM pulmonary disease, the appropriate guideline-based treatments are essential, and clinical studies to evaluate new or repurposed drugs are urgently needed.

KEYWORDS:

• Nontuberculous mycobacteria
• Mycobacterium avium complex
• mycobacterium abscessus
• mycobacterium kansasii
• antibiotic resistance

Article Highlights

• Drug-resistant nontuberculous mycobacterial pulmonary disease (NTM-PD) is difficult to treat.

• Development of macrolide resistance in patients with Mycobacterium avium complex (MAC)-PD can result in disease that is refractory to antibiotic treatment with a poor treatment outcome and high mortality.

• To treat macrolide-resistant MAC-PD, use of intravenous or inhaled amikacin, including newly developed amikacin liposomal inhalation suspension, and clofazimine as well as surgical resection should be considered.

• Amikacin-resistant MAC-PD could be an important issue especially in patients with advanced cavitary disease or macrolide-resistant MAC-PD because it can worsen treatment outcomes in these patients.

• M. abscessus can have intrinsic or acquired macrolide resistance, and very poor outcomes are associated with PD caused by M. abscessus subspecies abscessus with intrinsic inducible or acquired macrolide resistance or by M. abscessus subspecies massiliense with acquired macrolide resistance.

• Rifampin is the most important drug for M. kansaii-PD, and development of resistance against this drug might worsen treatment outcomes.

Development of resistance against effective antibiotics is a very important issue in the treatment of NTM-PD; to overcome this issue, guideline-based proper treatments and development of new drugs are needed.

Declaration of interest

Dr. Charles L. Daley has received grants from Insmed, Inc., and served on Advisory Boards for Otsuka, Insmed, Johnson and Johnson, Spero, and Horizon, not associated with the submitted work. Dr. Won-Jung Koh has received a consultation fee from Insmed for the Insmed Advisory Board Meeting, not associated with the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This study was funded by the Medical Research Fund of the Samsung Medical Center (OTC1180011), and by the National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (NRF-2018R1A2A1A05018309).