Prophylactic and therapeutic activities of azithromycin in a mouse model of pneumococcal pneumonia.

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.

• Authors: E Azoulay-Dupuis, E Vallée, J P Bedos, M Muffat-Joly, J J Pocidalo
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 35 Issue 6 Pg. 1024-8 (Jun 1991) ISSN: 0066-4804 [Print] United States
• PMID: 1656849 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Erythromycin
• Azithromycin

Topics

• Animals
• Azithromycin
• Blood (microbiology)
• Drug Evaluation, Preclinical
• Erythromycin (analogs & derivatives, pharmacokinetics, therapeutic use)
• Female
• Lung (microbiology)
• Mice
• Mice, Inbred C57BL
• Pneumonia, Pneumococcal (drug therapy, metabolism, microbiology, prevention & control)