Griffith, David E.

Abstract With only 9105 new US tuberculosis (TB) cases reported in 2017, expert consultation is essential for TB care. Data were captured 2013–2017 from consultations by 5 CDC-funded centers, now the TB Centers of Excellence (COEs). 14 586 consultations were provided to TB providers, most related to TB disease and treatment regimens.

Abstract 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 at least 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 three 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 (odds ratio, 4.22; 95% confidence interval, 2.08–8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 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 registered with www.clinicaltrials.gov (NCT02344004).

Abstract Rationale Staphylococcus aureus is commonly cultured from the sputum of patients with bronchiectasis; however, little is known about the prevalence of the organism in these patients, the characteristics of patients who have grown the organism, or its implications. Objectives Determine the relationship between S. aureus and pulmonary function, frequency of exacerbations, and frequency of hospitalization in patients with bronchiectasis Methods The Bronchiectasis Research Registry is a database of adults with non–cystic fibrosis bronchiectasis identified from 13 sites within the United States. Baseline and follow-up demographic, spirometric, microbiologic, and therapeutic data were entered into a central web-based database. Patients were grouped into three cohorts based on their previous respiratory cultures at the time of entry into the Registry: 1) no prior S. aureus or glucose-nonfermenting gram-negative bacilli (NF-GNB) (Pseudomonas, Stenotrophomonas, or Burkholderia spp.); 2) prior S. aureus at least once; or 3) no prior S. aureus but prior NF-GNB at least once. The association between S. aureus isolation and pulmonary function and frequency of exacerbations and hospital admissions was assessed, both at baseline and after 1 year of follow-up. Results S. aureus was cultured from 94 of 830 patients (11.3%) included in the analysis. Patients who had grown S. aureus before entry into the Registry had a frequency of prior exacerbations and baseline pulmonary function that was between that of patients who had grown NF-GNB and those who had grown neither NF-GNB or S. aureus. Similarly, at the first follow-up visit after study entry, patients who had grown S. aureus had a frequency of exacerbations and hospitalizations that was between those of patients who had grown NF-GNB and those who had grown neither NF-GNB nor S. aureus. However, in multivariate analysis, S. aureus was not associated with pulmonary function, frequency of exacerbation, or hospital admissions. There were no significant differences in patient characteristics or outcomes between patients who had methicillin-sensitive and methicillin-resistant S. aureus. Conclusions Staphylococcus aureus does not appear to be an independent risk factor for severe disease in patients with bronchiectasis enrolled in the Bronchiectasis Research Registry.

Abstract Nontuberculous mycobacteria (NTM) cause an increasingly important chronic and debilitating lung disease in older adults. Diagnosis is often delayed, although awareness among clinicians and patients is increasing. When necessary, treatment often lasts 18–24 months and consists of three or four antibiotics that can have serious side effects. Relapses are common and commonly require resumption of prolonged therapy. Given the need for improved diagnostic techniques and clinical trials to identify new therapies or to improve existing therapies, a group of North American clinicians and researchers formed the NTM Research Consortium (NTMRC) in 2014. The NTMRC recognized the importance of including the patient voice in determining research priorities for NTM. In November 2015, patients, caregivers, patient advocates, clinical experts, and researchers gathered for a 1-day meeting in Portland, Oregon funded by the Patient-Centered Outcomes Research Institute. The meeting goal was to define patient-centered research priorities for NTM lung infections. Patients expressed frustration with the number of people who have endured years of missed diagnoses or inadequate treatment of NTM. Participants identified as top research priorities the prevention of NTM infection; approval of more effective treatments with fewer side effects and easier administration; understanding the best chest physiotherapy methods; validating and using tools to measure quality of life; and developing a disease-specific activity and severity assessment tool. Workshop participants agreed that two complementary objectives are critical to ensure the best achievable outcomes for patients: (1) additional clinician education to improve screening and diagnosis of NTM infections; and (2) development of a geographically distributed network of experts in NTM disease to offer consultation or direct therapy after a diagnosis is made.

Abstract Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate. Objectives To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000–2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-γ treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed. Results Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5–11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7–9.2) and HRCT response by 4.9 times (95% CI, 1.9–13.0). Culture response was 1.5 times (95% CI, 1.1–2.2) higher for older subjects and 2.2 times (95% CI, 1.0–4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1–5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7–11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0–2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times. Conclusions TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.