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.
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.
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?
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.
The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold ...In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI;
= 39) or active TB infection (
= 3), and in health care workers (HCWs;
= 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients
> 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.
The prevalence of nontuberculous mycobacterial (NTM) lung disease is increasing in the USA. Clinicians are therefore encountering these patients with increasing frequency, with the attendant multiple ...therapeutic challenges presented by NTM lung disease including relatively frequent (compared with tuberculosis) treatment failure.
Critical elements for the successful treatment of Mycobacterium avium complex (MAC) lung disease include aggressive first therapeutic attempts and avoidance of the emergence of macrolide-resistant MAC strains, which are associated with worse treatment response and increased mortality. Reliably effective therapy for M. abscessus lung disease remains elusive but still usually requires parenteral agents. Lung resection surgery for selected patients is an important adjunct for both MAC and M. abscessus lung disease. Aside from surgery and parenteral antibiotics, there are very few data to support the efficacy of other drugs or interventions for patients who have failed the first-line therapy.
Clinicians who manage NTM lung disease will inevitably encounter patients who fail the first-line therapy. The choices for effective treatment of these patients are depressingly sparse. It is critically important to avoid creation of macrolide-resistant MAC strains and to carefully choose those NTM lung disease patients who will benefit from surgery.
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