Pharmacology Update

Aztreonam for Inhalation (Cayston®)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.

The FDA has approved a new inhaled antibiotic to treat cystic fibrosis (CF) patients infected with Pseudomonas aeruginosa. Aztreonam is a monobactam antibacterial active against gram-negative bacteria including Pseudomonas species. The drug is marketed by Gilead Sciences as Cayston®.

Indications

Aztreonam inhalation is indicated to improve respiratory symptoms in CF patients with P. aeruginosa.

Dosage

The recommended dose is 75 mg administered three times a day by inhalation for 28 days. Aztreonam is to be administered only with the Altera® Nebulizer System. A short-acting β2-agonist should be administered about 15 minutes before aztreonam administration.

Potential Advantages

Aztreonam significantly improves respiratory symptoms and pulmonary function in CF patients infected with P. aeruginosa in the airways.1,2 Aztreonam is an alternative to tobramycin as inhalation therapy. Drug administration takes 2-3 min compared to about 15 min for tobramycin.

Potential Disadvantages

Cross sensitivity to aztreonam may occur in patients with a history of allergy to β-lactam antibiotics (e.g., penicillin, cephalosporins).1 Bronchospasm has been associated with nebulized aztreonam therapy. A 15% reduction in forced expiratory volume in 1 second (FEV1) occurred in 3% of patients pretreated with a bronchodilator..1

Comments

Aztreonam is a monobactam antibiotic that exerts its antibacterial action by binding to the penicillin-binding proteins of bacteria. It is the first antibiotic to be approved for use in CF patients in more than a decade. Aztreonam inhalation was evaluated in a randomized, double-blind, placebo-controlled study in patient with CF with a P. aeruginosa airway infection (n = 164).1,2 Subjects were ≥ age 6 years with FEV1 between 25% and 75% predicted values and no recent use of antipseudomonal antibiotics or azithromycin. They were randomized to aztreonam 75 mg three times a day for 28 days or placebo. The primary endpoint was change in patient-reported respiratory symptoms as assessed using the CF-Questionnaire-Revised (CFQ-R). Secondary endpoints included changes in pulmonary function (FEV1), sputum P. aeruginosa (PA) density, and nonrespiratory CFQ-R scales. After 28 days, aztreonam improved the mean CFQ-R by 9.7 points and FEV1 by 10.3% predicted, and reduced the PA density by -1.45 log10 cfu/g compared to placebo. There was a trend toward fewer patients hospitalized (5% vs 14%) and fewer hospitalized days (0.5 days vs 1.5 days) in the aztreonam group. Productive cough was reduced by one-half compared to placebo. No changes in susceptibility of P. aeruginosa were observed following a 28-day treatment course. Aztreonam inhalation was generally well tolerated. There currently are no published data comparing inhaled aztreonam compared to inhaled tobramycin.

Clinical Implications

CF is an autosomal recessive disease that is the result of a mutation in the gene that encodes the protein cystic fibrosis transmembrane conductance regulator and affects the ion channels in the cell membrane. This leads to the accumulation of thick mucus in the lung and provides a favorable environment for bacterial colonization, especially P. aeruginosa. Aerosol tobramycin has been commonly used to eradicate P. aeruginosa airway infections and has been the only FDA-approved inhaled antibiotic available since 1997. In recent years there has been an increase in tobramycin-resistant P. aeruginosa.3 Aztreonam provides an alternative to tobramcyin for patients with CF and chronic P. aeruginosa airway infection.

References

1. Cayston Prescribing Information. Foster City, CA: Gilead Sciences, Inc.; February 2010.

2. Retsch-Bogart GZ, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest 2009;135:1223-1232.

3. Emerson J, et al. Changes in cystic fibrosis sputum microbiology in the United States between 1995 and 2008. Pediatr Pulmonol 2010;45:363-370.