Marras, Theodore K.

Purpose Specific classes of antibiotics, such as aminoglycosides, have well-established adverse events producing permanent hearing loss, tinnitus, and balance and/or vestibular problems (i.e., ototoxicity). Although these antibiotics are frequently used to treat pseudomonas and other bacterial infections in patients with cystic fibrosis (CF), there are no formalized recommendations describing approaches to implementation of guideline adherent ototoxicity monitoring as part of CF clinical care. Method This consensus statement was developed by the International Ototoxicity Management Working Group (IOMG) Ad Hoc Committee on Aminoglycoside Antibiotics to address the clinical need for ototoxicity management in CF patients treated with known ototoxic medications. These clinical protocol considerations were created using consensus opinion from a community of international experts and available evidence specific to patients with CF, as well as published national and international guidelines on ototoxicity monitoring. Results The IOMG advocates four clinical recommendations for implementing routine and guideline adherent ototoxicity management in patients with CF. These are (a) including questions about hearing, tinnitus, and balance/vestibular problems as part of the routine CF case history for all patients; (b) utilizing timely point-of-care measures; (c) establishing a baseline and conducting posttreatment evaluations for each course of intravenous ototoxic drug treatment; and (d) repeating annual hearing and vestibular evaluations for all patients with a history of ototoxic antibiotic exposure. Conclusion Increased efforts for implementation of an ototoxicity management program in the CF care team model will improve identification of ototoxicity signs and symptoms, allow for timely therapeutic follow-up, and provide the clinician and patient an opportunity to make an informed decision about potential treatment modifications to minimize adverse events. Supplemental Material https://doi.org/10.23641/asha.16624366

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 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.