Aksamit discusses the study of Kim et al which have further expanded an increasing body of literature of predicting outcomes, namely mortality, in patients with nontuberculous mycobacterial (NTM) ...pulmonary disease (PD). The findings will clearly potentially aid clinicians and researchers alike in recommendations to guide best care for patients with NTM PD. Despite these findings providing one important step forward, several more steps are needed to address unanswered questions, clarify findings, and leverage opportunities brought forward regarding NTM PD. First and foremost, the decision to start or hold treatment for an established diagnosis of NTM PD is complex and requires robust communication between patients and providers guided by a risk-benefit assessment of treatment as well as adjudication of expectations of goals of care.
Non-cystic fibrosis (CF) bronchiectasis ("bronchiectasis") is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory ...infections in chronic users of inhaled corticosteroids (ICSs)
macrolide monotherapy.
We identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models.
We identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23-1.57) for hospitalised respiratory infection, 1.56 (95% 1.49-1.64) for acute exacerbation and 1.09 (95% 0.95-1.25) for mortality.
Among patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.
Management of Mycobacterium avium complex (MAC) lung disease is complicated, frequently unsuccessful, and frustrating to patients and clinicians. The initial treatment effort may not be directed ...solely at MAC infection, rather it is often initiating airway clearance measures for bronchiectasis. The next important steps are deciding who to treat and when to initiate therapy. Definitive or unambiguous guidance for these decisions is often elusive. The evidence supporting the current macrolide-based regimen for treating MAC lung disease is compelling. This regimen has been recommended in consensus nontuberculous mycobacterial treatment guidelines from 1997, 2007, and 2020, although clinician compliance with these recommendations is inconsistent. Understanding the idiosyncrasies of MAC antibiotic resistance is crucial for optimal antibiotic management. As a corollary, the importance of avoiding development of macrolide resistance due to inadequate therapy cannot be overstated. An inhaled liposome amikacin preparation is now approved for treating refractory MAC lung disease and holds promise for an even broader role in MAC therapy. Surgery is also an important therapeutic adjunct for selected patients. Microbiologic recurrences due either to new infection or treatment relapse/failure are common and require the same level of rigorous assessment and clinical judgment for determining their significance as initial MAC isolates. In summary, treatment of patients with MAC lung disease is rarely straight forward and requires familiarity with multiple factors directly and indirectly related to MAC lung disease. The many nuances of MAC lung disease therapy defy simple treatment algorithms; however, with patience, attention to detail, and perseverance, the outcome for most patients is favorable.
BACKGROUND Bedaquiline is an oral antimycobacterial agent belonging to a new class of drugs called diarylquinolines. It has low equivalent minimal inhibitory concentrations for Mycobacterium ...tuberculosis and nontuberculous mycobacterial (NTM) lung disease, especially Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mab). Bedaquiline appears to be effective for the treatment of multidrug-resistant TB but has not been tested clinically for NTM disease. METHODS We describe a case series of off-label use of bedaquiline for treatment failure lung disease caused by MAC or Mab. Only patients whose insurance would pay for the drug were included. Fifteen adult patients were selected, but only 10 (six MAC, four Mab) could obtain bedaquiline. The 10 patients had been treated for 1 to 8 years, and all were on treatment at the start of bedaquiline therapy. Eighty percent had macrolide-resistant isolates (eight of 10). The patients were treated with the same bedaquiline dosage as that used in TB trials and received the best available companion drugs (mean, 5. 0 drugs). All patients completed 6 months of therapy and remain on bedaquiline. RESULTS Common side effects included nausea (60%), arthralgias (40%), and anorexia and subjective fever (30%). No abnormal ECG findings were observed with a mean corrected QT interval lengthening of 2. 4 milliseconds at 6 months. After 6 months of therapy, 60% of patients (six of 10) had a microbiologic response, with 50% (five of 10) having one or more negative cultures. CONCLUSIONS This small preliminary report demonstrates potential clinical and microbiologic activity of bedaquiline in patients with advanced MAC or Mab lung disease but the findings require confirmation with larger studies.
The study reported in this issue of the Journal by Jhun and colleagues (pp. 1322-1330) has, at one level, immediate patient management implications, but at another level, it raises fundamental ...questions about the relationship between MAC lung disease and underlying conditions such as bronchiectasis. ...the authors again demonstrate the importance of apparent MAC reinfection during and after a course of ostensibly adequate MAC therapy (2, 6). ...the authors found that few patients, just 3% of the original cohort and 22% of the culture positive persisters, developed macrolide-resistant MAC isolates. David E. Griffith, M.D. Pulmonary Infectious Disease Section University of Texas Health Science Center Tyler, Texas Timothy R. Aksamit, M.D. Pulmonary Diseases and Critical Care Medicine Mayo Clinic Rochester, Minnesota Originally Published in Press as DOI: 10.1164/rccm.201807-1243ED on August 9, 2018 References 1.Jhun BW, Kim S-Y, Moon SM, Jeon K, Kwon OJ, Huh HJ, et al.
Although nontuberculous mycobacterial pulmonary disease is increasing in incidence, outcomes remain less than optimal highlighting the unmet need for developing novel therapies.
Several new ...antibiotic formulations, novel antibiotics, and novel nonantibiotic treatments have recently demonstrated positive results in treating nontuberculous mycobacterial pulmonary disease.
Promising novel therapies are currently under investigation fueling much needed interest and enthusiasm in the nontuberculous mycobacterial pulmonary disease space and will hopefully lead to improved understanding and outcomes in this complex disease.
We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR).
The BRR is a database of patients with non-cystic-fibrosis ...bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet-based database. Patients were subsequently analyzed by the presence of NTM.
We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty-three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty-one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree-in-bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM.
Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.
Summary This review will utilize essential questions about nontuberculous mycobacterial (NTM) lung disease to succinctly address important new developments in the pathogenesis, diagnosis and ...management of NTM lung disease with a focus on practical information and “bottom line” answers. 1) What do I tell my patients who ask, “where did I get this infection” and, “should I take showers”? 2) What is the connection between bronchiectasis and the acquisition of NTM lung infection? 3) What other factors are important in the pathogenesis of NTM lung disease? 4) Why does it seem that am I seeing more new NTM lung disease patients? 5) Why is the diagnosis of NTM lung disease so complicated and does the diagnosis of NTM lung infection obligate specific treatment? 6) Unlike traditional tuberculosis, what is behind the irrelevance of most in vitro susceptibility testing reports for NTM infections? 7) Is there anything new for the management of patients with Mycobacterium avium complex lung disease? How does the radiographic appearance influence treatment? 8) Is there anything new for the management of patients with Mycobacterium abscessus lung disease? 9) What about the management of other NTM respiratory pathogens? 10) Is there a role for the use of macrolide monotherapy for non-cystic fibrosis bronchiectasis?
Bronchiectasis is an increasingly common chronic inflammatory airway disease. There is an urgent need to understand the epidemiology of bronchiectasis in older adults. We describe the prevalence and ...characteristics of patients with bronchiectasis within the US Medicare population.
Among the 40% of Medicare enrollees with prescription drug plans from 2006 to 2014, we identified patients ≥ 65 years of age with bronchiectasis by International Classification of Diseases, Ninth Revision, Clinical Modification claims (494.0 or 494.1) from a pulmonologist and no claim for cystic fibrosis. We calculated the prevalence from 2012 to 2014. Incident or newly diagnosed patients were those enrolled in Medicare at least 12 months prior to the first bronchiectasis diagnosis. We described clinical and health-care utilization characteristics for this cohort during the prior 12-month (baseline) period, and explored differences between those with and without a COPD diagnosis.
We identified 252,362 patients with bronchiectasis meeting all eligibility criteria. The average annual prevalence from 2012 to 2014 was 701 per 100,000 persons. Newly diagnosed patients were a mean age of 76 years, predominately women (65%), and predominately white, non-Hispanic (84%). During the baseline period, 12% were hospitalized for respiratory infections. Fifty-one percent had a dual diagnosis of COPD. Newly diagnosed patients with bronchiectasis and COPD had significantly different characteristics and utilization, for example were more likely hospitalized for respiratory infections during the baseline period (16% vs 7%) and to have a smoking history (46% vs 17%) compared with those without a dual COPD diagnosis, respectively.
We confirmed a high prevalence of bronchiectasis in the United States and significant heterogeneity in patients with bronchiectasis with and without COPD that should be further explored.
Martinez-Garcia et al examine the use of clinical fingerprinting to address the complexity and heterogeneity of bronchiectasis (BE) in practice. Scientific interest in BE has grown mainly due to the ...increase in prevalence, data obtained from large international BE registries, increased number of therapeutic clinical trials, and the negative impact of the disease (and of those triggered by it and associated with it) on a patient's prognosis and quality of life. The term BE describes a clinical syndrome that can be characterized by chronic respiratory symptoms and permanent dilation of the airways due to multiple etiologies, including postinfectious, idiopathic chronic obstructive pulmonary disease, asthma, allergic bronchopulmonary aspergillosis, immune deficiencies, primary ciliary dyskinesia, systemic inflammatory diseases, and alpha-1 antitrypsin deficiency, among others.
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