Can an antibiotic (macrolide) prevent Chlamydia pneumoniae-induced atherosclerosis in a rabbit model?
There is increasing data implicating Chlamydia pneumoniae in the pathogenesis of atherosclerosis, and antibiotics may theoretically be useful to prevent secondary vascular complications. Three groups of New Zealand White specific-pathogen-free rabbits, fed cholesterol-free chow, were inoculated via the nasopharynx on three occasions, 2 weeks apart, with C. pneumoniae. Group I (n = 23) rabbits were untreated; group II (n = 24) rabbits were treated with azithromycin at 30 mg/kg of body weight daily for 3 days and then once every 6 days, starting 5 days after first inoculation and continuing until sacrifice (early treatment); and group III (n = 24) rabbits were treated with the same dose of azithromycin but initiated 2 weeks after the last inoculation. All animals were sacrificed at 10 to 11 weeks after initial inoculation and examined for signs of atherosclerosis of the aorta. Eight (34.8%) untreated rabbits developed early signs of atherosclerosis, whereas only one (4.2%) in the early-treatment group had such signs (P = 0.02). However, eight rabbits (33.3%) of the delayed-treatment group had atherosclerotic changes of the aorta and no significant reduction compared to untreated rabbits. Early treatment of C. pneumoniae-infected rabbits with azithromycin was highly effective (87%) in preventing atherosclerotic changes, but delayed treatment was ineffective. It is possible that longer or more aggressive antibiotic treatment may be needed to reverse preformed lesions or that antibiotics may not be of value once lesions have formed.
Fong
I W
IW
Departments of Medicine, Laboratory Medicine and Pathology, St. Michael's Hospital, University of Toronto, Toronto, Canada. fongi@smh.toronto.on.ca
Chiu
B
B
Viira
E
E
Jang
D
D
Fong
M W
MW
Peeling
R
R
Mahony
J B
JB
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000907:Antibodies, Bacterial / Q000097:blood; D001011:Aorta / Q000382:microbiology / Q000473:pathology; D001170:Arthritis, Infectious / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D017963:Azithromycin / Q000494:pharmacology*; D002690:Chlamydia Infections / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology; D016993:Chlamydophila pneumoniae; D004195:Disease Models, Animal; D008297:Male; D011817:Rabbits
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D017963:Azithromycin