Once-weekly azithromycin in cystic fibrosis with chronic Pseudomonas aeruginosa infection.

Author(s): Steinkamp G, Schmitt-Grohe S, Doring G, Staab D, Pfrunder D, Beck G, Schubert R, Zielen S

Affiliation(s): CF-Centre Hamburg-Altona and Clinical Research Hannover, Germany. steinkamp@med-wiss.com

Publication date & source: 2008-11, Respir Med., 102(11):1643-53. Epub 2008 Aug 12.

Publication type: Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Data on the effects of long-term treatment with azithromycin (AZM) on inflammatory markers in cystic fibrosis patients chronically infected with Pseudomonas aeruginosa are scarce. So far there is no pharmacokinetic and clinical data on once-weekly dosage of AZM in CF patients. METHODS: In a randomised double-blind, placebo-controlled trial, patients received AZM or placebo 1 per week for 8 weeks (AZM dosage--20-29 kg: 500 mg, 30-39 kg: 750 mg, 40-49 kg: 1000 mg and > or = 50 kg: 1250 mg) after a course of intravenous antipseudomonal antibiotics. Pulmonary function tests, the serum markers LPS-binding protein (LBP), interleukin-8 (IL-8), CRP, P. aeruginosa alginate in sputum samples and quality of life scores were evaluated. RESULTS: Thirty-eight patients (21 AZM/17 placebo) (mean age: 23.7 years; mean FEV(1): 62% of predicted) were recruited. After treatment (mean dose of 21.2 mg/kg body weight once a week) pulmonary function declined in both groups compared to baseline (i.e. after cessation of i.v. antibiotics). The AZM group was significantly better for mean changes in serum CRP (AZM: +0.9 mg/l, placebo: +21.6 mg/l, p=0.019), lipopolysaccharide binding protein in serum, LBP (AZM: +0.9 microg/ml, placebo: +7.0 microg/ml, p=0.015), serum interleukin-8 (AZM: -3.1 pg/ml, placebo: +2.9 pg/ml, p=0.001) and alginate in sputum (AZM: +85 microg/ml, placebo: +353 microg/ml, p=0.048). Quality of life was significantly better after AZM and there was no increase in treatment-related adverse events. CONCLUSION: Once-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of i.v. antibiotics could not be prevented.