Affiliation:
1. Hôpital Claude Bernard, Institut National de la Santé et de la Recherche Médicale U.13, Paris, France.
Abstract
Azithromycin is a new acid-stable 15-membered-ring macrolide that exhibits an extended half-life and excellent tissue distribution, including distribution in the lung. We compared its in vivo activity with that of erythromycin using two models of Streptococcus pneumoniae pneumonia, namely, a model of acute infection in Swiss mice and a model of subacute infection in C57BL/6j mice. Female mice were infected by oral delivery into the trachea of 10(5) CFU of a virulent serotype 3 strain of S. pneumoniae (P 4241). Prophylactic and therapeutic treatments were given orally (p.o.) or subcutaneously (s.c.) by various regimens. In the model of subacute infection, a single dose of azithromycin, 25 mg/kg, given p.o. 7 h before infection protected 92% of the mice, while erythromycin was completely ineffective. In the model of acute infection, a single dose of azithromycin, 50 mg/kg, given s.c. 24 h prior to challenge protected 80% of the mice, whereas only 35% of the mice survived with erythromycin, 50 mg/kg, 1 h before challenge. Therapy, which was studied exclusively in the model of subacute infection, was initiated 48 h postinfection. Two doses of 12.5 mg/kg given p.o. 12 h apart resulted in 80% survival of mice treated with azithromycin versus 7% survival of mice treated with erythromycin. Pulmonary clearance of bacteria was consistent with the survival rates. Two doses (25 mg/kg) of azithromycin given s.c. at 48 and 65 h after infection led to complete clearance of bacteria from the lungs and blood, whereas erythromycin-treated mice remained bacteremic. The pharmacokinetics of azithromycin account for its superior efficacy against S. pneumoniae pneumonia relative to the efficacy of erythromycin.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
51 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献