title: Open label study of inhaled aztreonam for Pseudomonas eradication in children with cystic fibrosis: The ALPINE study.
abstract: BACKGROUND
  Consensus 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.
  
  
  METHODS
  CF patients (3 months to <18 years) with new onset Pa infection were treated with AZLI 75 mg 3 times daily for 28 days. 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 (≥ 2 cultures/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.
  
  
  RESULTS
  A total of 105 pediatric CF patients enrolled (3 months to <2 years, n=24; 2 to <6 years, n=25; 6 to <18 years, 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 4 weeks 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.
  
  
  CONCLUSIONS
  AZLI 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.
authors.affiliation: Erasmus MC-Sophia, University Medical Center, PO Box 2060, 3000 CB Rotterdam, The Netherlands. Electronic address: H.Tiddens@Erasmusmc.nl.
authors.forename: H A W M
authors.initials: HA
authors.lastname: Tiddens
authors.affiliation: University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: De Boeck
authors.affiliation: Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Clancy
authors.affiliation: CHU de Bordeaux, Bordeaux INSERM - CIC 0005, France.
authors.forename: M
authors.initials: M
authors.lastname: Fayon
authors.affiliation: University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands.
authors.forename: Arets
authors.initials: A
authors.lastname: H G M
authors.affiliation: Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bresnik
authors.affiliation: Gilead Sciences, 333 Lakeside Dr., Foster City, CA 94404, USA.
authors.forename: A
authors.initials: A
authors.lastname: Derchak
authors.affiliation: Gilead Sciences, 199 E. Blaine St., Seattle, WA 98102, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Lewis
authors.affiliation: Children's Mercy Hospitals and Clinics, 2401 Gillham Road, Kansas City, MO 64108, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Oermann
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D001398:Aztreonam / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam
keywords: Aerosolized antibiotics; Antipseudomonal; P. aeruginosa; Pediatric; Respiratory infections