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Antimicrobial Agents and Chemotherapy, September 1998, p. 2385-2390, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Dynamics of Clarithromycin and Azithromycin Efficacies against Experimental Haemophilus influenzae Pulmonary Infection

J. D. Alder,1,* P. J. Ewing,1 A. M. Nilius,2 M. Mitten,1 A. Tovcimak,1 A. Oleksijew,1 K. Jarvis,1 L. Paige,1 and S. K. T. Tanaka2

Experimental Therapeutics and Pharmacology,1 and Infectious Diseases Microbiology,2 Abbott Laboratories, Abbott Park, Illinois

Received 6 November 1997/Returned for modification 8 January 1998/Accepted 10 June 1998

The dynamics of clarithromycin and azithromycin efficacy against pulmonary 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 µg/ml) concentration of clarithromycin. The two macrolides demonstrated markedly different pharmacokinetic characteristics, with clarithromycin present in both blood and tissue, while azithromycin was concentrated primarily in tissue. During pulmonary infection in rats, H. influenzae was found in both intracellular locations and an extracellular location in the lung. Blood concentrations of clarithromycin and azithromycin approximated human pharmacokinetics, and the blood concentrations for either macrolide rarely exceeded MICs for H. influenzae. At dosages producing blood concentrations similar to values achieved clinically, clarithromycin produced efficacy on day 3 of therapy, while both clarithromycin and azithromycin were equally effective on day 7. The different dynamics of clarithromycin and azithromycin suggest that length of therapy should be considered as a key parameter in evaluations of drug efficacy.

* Corresponding author. Mailing address: Abbott Laboratories, Department 47T, Building AP-3, Abbott Park, IL 60064. Phone: (847) 937-0164. Fax: (847) 938-4777. E-mail: alderj{at}abbott.com.

Antimicrobial Agents and Chemotherapy, September 1998, p. 2385-2390, Vol. 42, No. 9
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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