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

SummaryBackgroundData 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.MethodsIn 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 ≥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.ResultsThirty-eight patients (21 AZM/17 placebo) (mean age: 23.7 years; mean FEV1: 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 IV 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 μg/ml, placebo: +7.0 μg/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 μg/ml, placebo: +353 μg/ml, p = 0.048). Quality of life was significantly better after AZM and there was no increase in treatment-related adverse events.ConclusionOnce-weekly azithromycin ameliorated inflammatory reactions and improved quality of life. A decline of pulmonary function after cessation of IV antibiotics could not be prevented.