Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis.
BACKGROUND
The effectiveness and safety of aztreonam lysine for inhalation (AZLI) in patients with cystic fibrosis (CF) on maintenance treatment for Pseudomonas aeruginosa (PA) airway infection was evaluated in this randomized, double-blind, placebo-controlled study.


OBJECTIVE
To evaluate the safety and efficacy of inhaled aztreonam lysine in controlling PA infection in patients with CF.


METHODS
After randomization and a 28-day course of tobramycin inhalation solution (TIS), patients (n = 211; > or =6 yr; > or =3 TIS courses within previous year; FEV(1) > or = 25% and < or =75% predicted values) were treated with 75 mg AZLI or placebo, twice or three times daily for 28 days, then monitored for 56 days. The primary efficacy endpoint was time to need for additional inhaled or intravenous antipseudomonal antibiotics. Secondary endpoints included changes in respiratory symptoms (CF Questionnaire-Revised [CFQ-R] Respiratory Scale), pulmonary function (FEV(1)), and sputum PA density. Adverse events and minimum inhibitory concentrations of aztreonam for PA were monitored.


RESULTS
AZLI treatment increased median time to need for additional antipseudomonal antibiotics for symptoms of pulmonary exacerbation by 21 days, compared with placebo (AZLI, 92 d; placebo, 71 d; P = 0.007). AZLI improved mean CFQ-R respiratory scores (5.01 points, P = 0.02), FEV(1) (6.3%, P = 0.001), and sputum PA density (-0.66 log(10) cfu/g, P = 0.006) compared with placebo; no AZLI dose-response was observed. Adverse events reported for AZLI and placebo were comparable and consistent with CF lung disease. Susceptibility of PA to aztreonam at baseline and end of therapy were similar.


CONCLUSIONS
AZLI was effective in patients with CF using frequent TIS therapy. AZLI delayed time to need for inhaled or intravenous antipseudomonal antibiotics, improved respiratory symptoms and pulmonary function, and was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00104520).
McCoy
Karen S
KS
Ohio State University, Nationwide Children's Hospital, Columbus, OH 43205, USA. karen.mccoy@nationwidechildrens.org
Quittner
Alexandra L
AL
Oermann
Christopher M
CM
Gibson
Ronald L
RL
Retsch-Bogart
George Z
GZ
Montgomery
A Bruce
AB
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001398:Aztreonam / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications* / Q000382:microbiology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D011788:Quality of Life; D012129:Respiratory Function Tests / Q000379:methods / Q000706:statistics & numerical data; D015610:Serum Bactericidal Test / Q000379:methods / Q000706:statistics & numerical data; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D000900:Anti-Bacterial Agents; D001398:Aztreonam