Open label study of inhaled aztreonam for Pseudomonas eradication in children with cystic fibrosis: The ALPINE study

Abstract

BackgroundConsensus guidelines recommend early treatment to eradicate newly acquired Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients although there is no single preferred regimen. Aztreonam for inhalation solution (AZLI) significantly reduces sputum Pa density in CF patients with chronic Pa infection and has been well tolerated in the pediatric population. This single-arm, open-label Aztreonam Lysine for Pseudomonas Infection Eradication (ALPINE) study was conducted to evaluate the safety and efficacy of a 28-day treatment course of AZLI to eradicate newly acquired Pa infection in pediatric CF patients. MethodsCF patients (3months to <18years) with new onset Pa infection were treated with AZLI 75mg 3 times daily for 28days. New onset Pa infection was defined as first lifetime Pa-positive respiratory tract culture (throat swab, sputum) or Pa-positive culture after a ≥2-year history of Pa-negative cultures (≥2cultures/year). Sputum or throat swab cultures were collected at study entry (baseline) and at weeks 4 (end of treatment), 8, 16, and 28. Primary endpoint was the percentage of patients with cultures negative for Pa at all post-treatment time points. ResultsA total of 105 pediatric CF patients enrolled (3months to <2years, n=24; 2 to <6years, n=25; 6 to <18years, n=56). Of the 101 patients who completed treatment, 89.1% (n=90) were free of Pa at the end of treatment and 75.2% (n=76) were free of Pa 4weeks after the end of treatment. Of the 79 patients evaluable for the primary endpoint, 58.2% were free of Pa at all post-treatment time points. ConclusionsAZLI was effective and well tolerated in eradicating Pa from newly infected pediatric patients with CF. These eradication rates are consistent with success rates reported in the literature for various antibiotic regimens, including other inhaled antibiotics studied for eradication.ClinicalTrials.gov: NCT01375049.