Azithromycin (CP-62,993) in acute exacerbations of chronic bronchitis: an open clinical, microbiological and pharmacokinetic study

A group of 21 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis was treated for five days with a new oral macrolide azithromycin. They received one dose of 500 mg on the first day, followed by 250 mg once daily thereafter. Pre-treatment sputum cultures were typical for this district, but the cultures during and after treatment showed many Haemophilus influenzae infections persisting. Geometric mean MICs of azithromycin for these organisms rose from 1.23 mg/l (pre-treatment) to 4.87 mg/l, a week after the end of treatment. The mean MICs for erythromycin also rose four-fold. Streptococcus pneumoniae and Branhamella catarrhalis strains were effectively eradicated. Pharmacokinetic studies on serum and sputum from the first treatment day showed relatively low serum Cmax values, averaging 0.63 mg/l, but with considerable individual variation. However, peak sputum concentrations averaged 3.7 mg/l. Nevertheless, the clinical and microbiological results were not encouraging because of the failure to eradicate H. influenzae with the drug dosage used in this study.