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: H A W M Tiddens, K De Boeck, J P Clancy, M Fayon, Arets H G M, M Bresnik, A Derchak, S A Lewis, C M Oermann, ALPINE study investigators
• Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society (J Cyst Fibros) Vol. 14 Issue 1 Pg. 111-9 (Jan 2015) ISSN: 1873-5010 [Electronic] Netherlands
• PMID: 25091537 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014. Published by Elsevier B.V.

Chemical References

• Anti-Bacterial Agents
• Aztreonam

Topics

• Administration, Inhalation
• Adolescent
• Anti-Bacterial Agents (administration & dosage)
• Aztreonam (administration & dosage)
• Child
• Child, Preschool
• Cystic Fibrosis (drug therapy, microbiology)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Humans
• Infant
• Male
• Pseudomonas Infections (diagnosis, drug therapy)
• Pseudomonas aeruginosa (drug effects, isolation & purification)
• Respiratory Tract Infections (drug therapy, microbiology)
• Severity of Illness Index
• Time Factors
• Treatment Outcome