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Antimicrobial Agents and Chemotherapy, August 2002, p. 2321-2326, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2321-2326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Influence of Clarithromycin on Early Atherosclerotic Lesions after Chlamydia pneumoniae Infection in a Rabbit Model

Ignatius W. Fong,1* Brian Chiu,2,{dagger} Esther Viira,1,2 Dan Jang,3 and James B. Mahony4

Departments of Medicine,1 Laboratory Medicine and Pathology, St. Michael's Hospital and University of Toronto,2 St. Joseph's Hospital,3 McMaster University, Toronto, M5B 1W8 Ontario, Canada4

Received 24 May 2001/ Returned for modification 25 November 2001/ Accepted 10 April 2002

Chlamydia pneumoniae may play a role in atherogenesis and vascular diseases, and antibiotics may prove useful in these conditions. Three groups of New Zealand White rabbits (24 per group) were infected via the nasopharynx with C. pneumoniae on three separate occasions (2 weeks apart). Group I was untreated and sacrificed at 12 weeks; group II received clarithromycin at 20 mg/kg/day for 8 days, beginning 5 days after each inoculation (early treatment); and group III received a similar dose of clarithromycin starting 2 weeks after the third inoculation and continued for 6 weeks thereafter (delayed treatment). To test for a possible anti-inflammatory effect of clarithromycin, two other groups of uninfected rabbits (12 animals in each) were fed 0.5% cholesterol-enriched chow, and one of these groups was treated with clarithromycin at 30 mg/kg/day for 6 weeks. Of 23 untreated infected rabbits, 8 developed early lesions of atherosclerosis, whereas 2 of the 24 early-treated group II had similar changes (P = 0.036 [75% efficacy]). However, in the delayed-treatment group, group III, 3 of 24 rabbits developed early lesions of atherosclerosis, thus demonstrating 62.5% reduction compared to the untreated controls (P = 0.07 [trend to statistical significance]). C. pneumoniae antigen was detected in 8 of 23 group I (untreated) rabbits versus 1 of 24 of the early-treated (group II) rabbits and 4 of 24 animals in the delayed group III (P = 0.009 and 0.138, respectively). All of the untreated, cholesterol-fed rabbits had moderate to advanced atherosclerosis (grade III or IV); clarithromycin had no effect on reducing the prevalence of but did reduce the extent of atherosclerosis in the cholesterol-fed rabbits by 17% compared to untreated controls. Thus, clarithromycin administration modified C. pneumoniae-induced atherosclerotic lesions and reduced the ability to detect organism in tissue. Early treatment was more effective than delayed treatment.

* Corresponding author. Mailing address: Division of Infectious Disease, St. Michael's Hospital, 30 Bond St., Rm. 4-179C, Toronto, Ontario M5B 1W8, Canada. Phone: (416) 864-5746. Fax: (416) 864-5310. E-mail: fongi{at}smh.toronto.on.ca.

{dagger} Present address: Department of Laboratory Medicine Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada.

Antimicrobial Agents and Chemotherapy, August 2002, p. 2321-2326, Vol. 46, No. 8
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.8.2321-2326.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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