Penetration of clarithromycin and its 14-hydroxy metabolite into middle ear effusion in children with secretory otitis media.

Clarithromycin suspension was given at a dosage of 7.5 mg/kg bd for 7 days to 31 children with secretory otitis media, scheduled for insertion of grommets. The fifth dose was given approximately 2.5 h before myringotomy and aspiration of the middle ear effusion at which time a blood sample also was taken. In addition, in 16 children blood samples were taken at 1, 1.5 and 4 h after the fifth dose. The concentrations of clarithromycin and its active 14-hydroxylated metabolite, in middle ear effusion and serum, were determined by HPLC. Before therapy, at surgery on day 3 and after completion of treatment, nasopharyngeal samples were taken for culture and susceptibility testing. In the middle ear effusions mean concentrations of clarithromycin (2.5 mg/L) and metabolite (1.3 mg/L) were considerably higher than the serum concentrations (1.7 and 0.8 mg/L, respectively). The mean concentrations in middle ear effusion exceeded the MICs for most respiratory pathogens. Complete eradication of Streptococcus pneumoniae, Moraxella catarrhalis and Streptococcus pyogenes from the nasopharynx was achieved after three days of therapy. Approximately 50% of the isolates of Haemophilus influenzae were eradicated from approximately 50% of the patients and the growth of the persisting strains was decreased from abundant or moderate to sparse. Adverse events were mild and transient and were experienced by only two of the 31 children.