Aztreonam lysine for inhalation: new formulation of an old antibiotic

The pharmacology, safety, efficacy, pharmacokinetics, pharmacodynamics, current place in therapy, and potential future therapeutic uses of inhaled aztreonam are reviewed.

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.

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.