Aztreonam Lysine for Inhalation

New Formulation of an Old Antibiotic

Kristen Zeitler, Brian Salvas, Vanessa Stevens, and Jack Brown

Disclosures

Am J Health Syst Pharm. 2012;69(2):107-115. 

In This Article

Abstract and Introduction

Abstract

Purpose The pharmacology, safety, efficacy, pharmacokinetics, pharmacodynamics, current place in therapy, and potential future therapeutic uses of inhaled aztreonam are reviewed.
Summary Inhaled aztreonam, a newly formulated lysine salt of the original monobactam antibiotic, is approved for the treatment of respiratory symptoms in patients with cystic fibrosis (CF) who are colonized with Pseudomonas aeruginosa. Its spectrum of activity is limited to susceptible gram-negative organisms, including P. aeruginosa. Lyophilized aztreonam lysine is diluted with 0.17% sodium chloride and administered using the Altera nebulizer system, which produces appropriate-sized particles for proper deposition in the lungs to achieve high sputum and low systemic concentrations. Mean sputum drug concentrations are highest 10 minutes after dose administration, and plasma concentrations peak one hour after inhalation. Aztreonam is excreted via active tubular secretion and glomerular filtration. Caution is advised in patients with renal or hepatic impairment, breastfeeding women, and patients age 65 years or older. Like the older i.v. formulation, inhaled aztreonam displays time-dependent killing. Phase III clinical trials have shown improvements in respiratory symptoms, decreased P. aeruginosa sputum density, prolonged time intervals between antibiotic treatments, and efficacy without the development of resistance in the face of repeated exposures. This formulation is available only from select specialty pharmacies and should only be used with the Altera nebulizer system.
Conclusion Inhaled aztreonam has shown efficacy and safety in patients seven years of age or older with CF who have P. aeruginosa airway infections. This product may complement existing therapies and offers the advantage of a new inhaled formulation to aid in treatment regimens.

Introduction

Cystic fibrosis (CF) is a chronic and difficult-to-manage auto-somal recessive disorder whose most debilitating manifestations are pulmonary symptoms due to chronic airway infections, one of which is Pseudomonas aeruginosa infection.[1,2] In patients with CF, chronic P. aeruginosa airway infections are associated with marked decline in pulmonary function, increased hospitalizations, and excessive mortality.[1,3] Aggressive treatment of such infections, coupled with a better understanding of underlying pathophysiology, likely contributed to an observed increase in patient life expectancies over the past four decades.[4] Disappointingly, no therapies are currently available for the treatment of the underlying mechanism of CF. Inhaled antibiotics are an important part of the maintenance drug regimens for many patients with CF.[1,3,4]

Airway colonization with P. aeruginosa in patients with CF is correlated with an increased risk of death.[2] Correspondingly, therapies aimed at managing P. aeruginosa airway colonization and subsequent infection may result in a significant reduction in mortality. Previous studies have demonstrated that inhaled anti-pseudomonal antibiotics have been associated with improvements in pulmonary function, as measured by forced expiratory volume in one second (FEV1);[5–7] decreased density of P. aeruginosa in the sputum;[5–7] fewer exacerbations;[5] and a lower risk of hospitalization.[6] Other studies have investigated the use of oral azithromycin for its antiinflammatory properties in patients with CF with and without P. aeruginosa airway infections.[8,9] Other antimicrobials used for the treatment of CF include colistin, tobramycin, gentamicin, carbenicillin, aztreonam, levofloxacin, and penicillin.[7,10–13] Durations of treatment have varied from episodic use for infectious exacerbations to chronic suppressive and eradicative therapy.[14] While inhaled antibiotics have proven beneficial in the long-term management of CF, many challenges remain. Currently marketed inhaled antibiotics are limited by long administration times (up to 15 minutes per dose), bronchospasm, airway irritation, and drug inactivation in the sputum.[7,15]

Inhaled aztreonam (Cayston, Gilead Sciences) is a newly formulated antipseudomonal monobactam antibiotic approved by the Food and Drug Administration (FDA) in February 2010 to improve respiratory symptoms in patients with CF who are colonized with P. aeruginosa.[16] This article reviews the pharmacology, clinical efficacy, and toxicity of inhaled aztreonam; addresses its potential utility in the management of select patients with CF; and highlights its potential future uses in the management of CF and other therapeutic areas.

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