| 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
(Affiliation: Hôpital Claude Bernard, Institut National de la Santé et de la Recherche Médicale U.13, Paris, France.)
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| Journal | Antimicrobial agents and chemotherapy
(Antimicrob Agents Chemother)
Vol. 35
Issue 6
Pg. 1024-8
(Jun 1991)
ISSN: 0066-4804 UNITED STATES |
| PMID | 1656849
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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| 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)
|
