Variability in the Management of Adults With Pulmonary Nontuberculous Mycobacterial Disease

Abstract

Background The increasing global prevalence of pulmonary nontuberculous mycobacteria (NTM) disease has called attention to challenges in NTM diagnosis and management. This study is conducted to understand management and outcomes of patients with pulmonary NTM disease at diverse centers across the US. Methods We conducted a 10-year (2005-2015) retrospective study at seven Vaccine and Treatment Evaluation Units to evaluate pulmonary NTM treatment outcomes in human immunodeficiency virus-negative adults. Demographic and clinical information were abstracted through medical record review. Microbiologic and clinical cure were evaluated using previously defined criteria. Results Of 297 patients diagnosed with pulmonary NTM, the most frequent NTM species were Mycobacterium avium-intracellulare complex (83.2%), M. kansasii (7.7%), and M. abscessus (3.4%). Two hundred forty-five (82.5%) patients received treatment, while 45 (15.2%) were followed without treatment. Eighty-six patients had available drug susceptibility results; of these, >40% exhibited resistance to rifampin, ethambutol, or amikacin. Of the 138 patients with adequate outcome data, 78 (56.5%) experienced clinical and/or microbiologic cure. Adherence to the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) treatment guidelines was significantly more common in patients who were cured (odds ratio [OR] 4.5, 95% confidence interval [CI] 2.0-10.4, P < 0.001). Overall mortality was 15.7%. Conclusions Despite ATS/IDSA Guidelines, management of pulmonary NTM disease was heterogeneous and cure rates were relatively low. Further work is required to understand which patients are suitable for monitoring without treatment and the impact of antimicrobial therapy on pulmonary NTM morbidity and mortality.

What is important for people with nontuberculous mycobacterial disease? An EMBARC-ELF patient survey

“…55% of those who are no longer being treated. This finding is in agreement with previously reported 'real life' studies, reporting cure rates as low as 27.6%(4) and 56.5% (2). Some of the symptoms that were rated by respondents as troublesome were found in the recently 'NTM module' QOL tool(5)-especially 'poor appetite' and 'fever'.…”

“…The treatment is lengthy, and the drugs used often associated with adverse effects. Adherence to NTM-pd management guidelines were found to be suboptimal, impacting treatment success (2), with substantial differences in physicians' decision to treat and in their adherence to treatment guidelines (2)(3)(4).…”

First-in-Human Evaluation of the Safety, Tolerability, and Pharmacokinetics of SPR720, a Novel Oral Bacterial DNA Gyrase (GyrB) Inhibitor for Mycobacterial Infections

“…Standard-of-care oral treatment includes azithromycin, rifampin, ethambutol, isoniazid, fluoroquinolones, doxycycline, linezolid, and trimethoprim-sulfamethoxazole ( 5 , 12 , 13 ). The administration of combinations of these drugs is required for treatment durations of up to 12 months following sputum culture conversion, and recurrence or reinfection occurs in approximately 50% of cases ( 4 , 25 , 26 ). In a recent retrospective study of 297 patients with NTM, 40% of patients who had susceptibility results available were resistant to amikacin, ethambutol, or rifampin ( 4 ).…”

“…In 2018, an estimated 75,000 to 105,000 people in the United States were diagnosed with NTM lung infection, with a higher frequency in older adults, and particularly in older nonsmoking women and men with COPD ( 2 , 3 ). The prevalence of NTM-PD is increasing worldwide and is associated with increased health care costs and poor outcomes ( 1 , 4 – 11 ).…”

“…Current treatment guidelines for NTM-PD recommend prolonged treatment for at least 12 months after culture conversion with a three-drug approach comprised of azithromycin and two other drugs (rifampin and ethambutol, streptomycin, or intravenous amikacin) ( 12 , 13 ). Even in the setting of prolonged combination therapy, outcomes are poor and often complicated by treatment-limiting adverse effects, resulting in high relapse and mortality rates ( 4 , 14 – 17 ). New effective treatment options for NTM are needed.…”