DYNAMICS OF CLARITHROMYCIN AND AZITHROMYCIN EFFICACIES AGAINST EXPERIMENTAL HAEMOPHILUS-INFLUENZAE PULMONARY INFECTION

The dynamics of clarithromycin and azithromycin efficacy against pulmo nary Haemophilus influenzae infection in rats were evaluated. Efficacy was measured by reduction in pulmonary H. influenzae burden on days 3 and 7 postinoculation, Clarithromycin therapy was effective on day 3 or 7 of therapy, while azithromycin was effective on day 7 but not on day 3 of therapy, Both macrolides produced marked efficacy against all six strains of H. influenzae tested, including four strains for which MICs were above the susceptible breakpoint (8 mu g/ml) concentration of clarithromycin, The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both b lood and tissue, while azithromycin was concentrated primarily in tiss ue. During pulmonary infection in rats, H. influenzae was found in bot h intracellular locations and an extracellular location in the lung. B lood concentrations of clarithromycin and azithromycin approximated hu man pharmacokinetics, and the blood concentrations for either macrolid e rarely exceeded MICs for H. influenzae. At dosages producing blood c oncentrations similar to values achieved clinically, clarithromycin pr oduced efficacy on day 3 of therapy, while both clarithromycin and azi thromycin were equally effective on day 7, The different dynamics of c larithromycin and azithromycin suggest that length of therapy should b e considered as a key parameter in evaluations of drug efficacy.