Background: The aim of this study was to investigate the extracellular concentration and the degree of sinus fluid penetration of newer macrolides, within the first 24-48 hours of treatment in patients with acute bacterial rhinosinusitis (ABRS), choosing clarithromycin and azithromycin as model antibiotics. An open, noninterventional pharmacokinetic study was performed at a tertiary teaching hospital.
Methods: In 36 outpatients with ABRS, sinus fluid aspirates and serum samples were collected 2, 4, 6, 8, and 12 hours or 2, 6, 12, and 24 hours after the administration of three doses of oral clarithromycin, 500 mg, twice daily or two doses of oral azithromycin, 500 mg, once daily, respectively. Drug concentrations were determined in both matrices by high-performance liquid chromatography with fluorometric detection, and the pH was estimated for all sinus fluid samples.
Results: The average clarithromycin sinus fluid concentration was found to be significantly higher than the corresponding azithromycin concentration (2.47 mg/L versus 0.65 mg/L), while the extent of the average sinus fluid penetration, expressed by the ratio of drug concentration in tissue versus serum, was similar for both drugs (115 and 120%, respectively).
Conclusion: In patients with ABRS, clarithromycin and azithromycin present adequate penetration into sinus fluid to eradicate erythromycin-sensitive strains of Streptococcus pneumoniae. Considering their comparative in vitro activity, the sinus fluid pH effect, and their sinus fluid penetration profile, we may conclude that among the erythromycin-resistant S. pneumoniae strains, clarithromycin might be advantageous over azithromycin in eradicating some of the low-level resistant strains.