RESUMEN
OBJECTIVES: As cystic fibrosis (CF) lung disease progresses, the airways become infected with opportunistic pathogens, such as Pseudomonas aeruginosa (PA). In October 2019, the US Food and Drug Administration approved elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective modulator therapy (HEMT), for individuals 12 years and older with 1 copy of the F508del cystic fibrosis transmembrane conductance regulator (CFTR) mutation. ETI increases the amount of and function of CFTR in the respiratory epithelium, improving mucociliary clearance and reducing static airway mucus, a major trigger for chronic infection and inflammation. METHODS: A retrospective analysis of inhaled tobramycin (iTOB) prescriptions between January 1, 2016, and December 31, 2021, was performed. This captured data before and after ETI approval at Children's Mercy Kansas City (CMKC). The number of individuals with new PA acquisition and individuals considered -chronically infected was analyzed. RESULTS: The number of eradication prescriptions declined in 2020 and 2021, with 15 (7%) and 12 (5%) -individuals prescribed therapy for those years, respectively. A similar pattern was observed for -prescriptions for chronic infection. A reduction was seen in 2020 and 2021, with 28 (13%) and 20 (9%) individuals -prescribed therapy for the respective years. CONCLUSIONS: The CMKC experienced a decrease in the number of courses of iTOB prescribed during the last 6 years. The reasons for this are likely multifactorial and may include the implementation of standardized PA surveillance and eradication protocols, the effect of HEMT on mucociliary clearance and airway microbiology, and the poorly understood effects of the SARS-CoV-2 pandemic on the epidemiology of respiratory infections.
RESUMEN
Patients with cystic fibrosis (CF) develop pulmonary disease secondary to airway infection and dysregulated inflammation. Therapeutic innovations such as nebulized antimicrobial therapy targeting specific pathogens have resulted in improvements in quality of life and life expectancy. Aztreonam lysine for inhalation (AZLI) solution was initially approved to improve respiratory symptoms in CF patients with Pseudomonas aeruginosa (PA) in 2010 by the Food and Drug Administration. Since then, research broadening labeling and clinical application has been developed. In this review, we analyze published and ongoing research regarding AZLI therapy in CF. A search of the Cochrane Database of Systematic Reviews and the PubMed and ClinicalTrials.gov databases was conducted to identify publications about AZLI. Three pre-approval studies were identified and assessed. Two are Phase 3, placebo-controlled trials, assessing a variety of safety and efficacy endpoints, leading to FDA approval. The third is an open-label extension of the two previous trials. An additional seven post-approval, completed trials were identified and are included in this review. They represent a variety of study designs including safety and efficacy in patients with mild lung disease and young patients, an active comparator trial vs inhaled tobramycin, an eradication study, a study among patients with Burkholderia cepacia, and a study assessing continuous alternating antibiotic therapy. Finally, five ongoing clinical trials are discussed. Overall, studies demonstrated that inhaled aztreonam is a safe and effective antimicrobial treatment for the eradication of newly acquired P. aeruginosa and long-term suppressive therapy of chronic endobronchial infection among people with cystic fibrosis.