Faculty Bibliography

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2.

Introduction: Treatment options for refractory MAC-LD are limited. By month 6 in CONVERT, culture conversion rates in adults with refractory MAC-LD were 29.0% (65/224) with ALIS, a nebulized, liposome-encapsulated amikacin formulation, + guideline-based therapy (GBT) vs 8.9% (10/112; P<.0001) with GBT alone.
Aim(s): We report safety, culture conversion durability, and functional response (6-minute walk test; 6MWT) with extended (up to 16 mo) ALIS therapy.
Method(s): In CONVERT, patients were randomly assigned to receive ALIS 590mg QD + GBT or GBT alone. Patients with culture conversion (3 consecutive monthly MAC-negative sputum cultures) by month 6 continued treatment for 12 months after the time of culture conversion.
Result(s): In patients who converted by month 6 and continued treatment, 63% (41/65) of those on ALIS+GBT and 30% (3/10) on GBT alone remained culture negative after 12 months of subsequent treatment; 63% (41/65) vs 0% (0/10) remained culture-negative 3 months off all antibiotics. There was no difference between treatment arms in the change in 6MWT distance from baseline to month 8 (P=0.84). Extended ALIS exposure did not alter overall safety findings (Griffith, AJRCCM 2018) with ALIS+GBT and GBT alone; respectively, 84.7% (195/223) and 50.9% (57/112) had respiratory treatment-emergent adverse events (TEAEs); 20.2% (45/223) and 20.5% (23/112) had serious TEAEs.
Conclusion(s): Addition of ALIS to GBT in patients with refractory MAC-LD improved culture conversion, which was maintained during therapy and for 3 months posttreatment. No new safety signals emerged with extended treatment

Objective/UNASSIGNED:This study compares and contrasts the clinical features of non-cystic fibrosis bronchiectasis with 3 uncommon disorders known to be associated with bronchiectasis but with distinctly different underlying defined pathophysiologic derangements, namely severe alpha-1 antitrypsin deficiency (AATD), common variable immunodeficiency (CVI) and primary ciliary dyskinesia (PCD). Methods/UNASSIGNED:The Bronchiectasis Research Registry provides a central database for studying patients with non-cystic fibrosis bronchiectasis. This report consists of information from 13 U.S. sites pertaining to the 3 study diagnoses. Patients with AATD (SZ and ZZ phenotypes only), CVI (patients with IgG≤500), PCD (history of physician diagnosed Kartagener's syndrome or PCD), and patients with confirmed absence of the above 3 diagnoses (idiopathic control group) were included in the study. Descriptive statistics were computed for the main demographic and clinical characteristics of the sample stratified by group. Values between the groups were compared using Kruskal-Wallis test, and Chi-squared/ Fisher's exact tests respectively. The significance level was set at 0.05. Software SAS 9.4 was used to perform the statistical analyses. Results/UNASSIGNED:were the organisms most commonly isolated from sputum. Mycobacterial infection was most commonly reported in those with AATD. Conclusion/UNASSIGNED:. A greater percentage of those with AATD reported mycobacterial lung involvement.

Rationale Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite ≥6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS+GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Measurements and Main Results Enrolled patients (ALIS+GBT, n=224; GBT-alone, n=112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS+GBT and 10 of 112 (8.9%) with GBT alone (OR, 4.22; 95% CI [2.08, 8.57]; P<0.001). Patients in the ALIS+GBT arm vs GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% CI, [2.00, 7.60]). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS+GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02344004.

Background: Aspiration is associated with non-tuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.Methods: 297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and a nested mycobacteriome sequencing approaches characterised microbiota composition. Inflammatory profiles of lower airway samples were also examined.Results: The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristic or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some non-pathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.Conclusions: The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples which are culture positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.

PURPOSE OF REVIEW/OBJECTIVE:To highlight recent original research and specialty society guidelines regarding the diagnosis and treatment of nontuberculous mycobacterial (NTM) pulmonary disease. RECENT FINDINGS/RESULTS:The prevalence of NTM pulmonary disease has risen in recent years. The prevalence of individual NTM species varies geographically, although Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC) remain among the most commonly encountered in many regions. Diagnosis and treatment of NTM pulmonary disease can be complex but guideline-based recommendations have been published. However, adherence to guideline recommendations is poor. Drug susceptibility testing plays a role with important caveats for treatment. Alternative therapies are being explored with older antimycobacterial drugs like clofazimine, which has demonstrated efficacy and tolerability for treatment-refractory NTM infections, and a novel formulation of amikacin for inhalation which may be better tolerated than parenteral administration. Several studies have shown that patients will have recurrences as high as 48%, and that these are not solely relapses but many cases are reinfections with a new organism. United States and European research registries of patients with non-cystic fibrosis bronchiectasis are expected to provide needed data on clinical characteristics of patients at risk for NTM pulmonary disease. SUMMARY/CONCLUSIONS:The evidence base for optimal management of NTM pulmonary disease is expanding but notable gaps in the literature remain.