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Antimicrobial Agents and Chemotherapy, November 2002, p. 3478-3483, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3478-3483.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Azithromycin on Shiga Toxin Production by Escherichia coli and Subsequent Host Inflammatory Response

Tatsuki Ohara,1,2 Seiichi Kojio,1 Ikue Taneike,1 Saori Nakagawa,1 Fumio Gondaira,1 Yukiko Tamura,1 Fumitake Gejyo,2 Hui-Min Zhang,1 and Tatsuo Yamamoto1*

Division of Bacteriology, Department of Infectious Disease Control and International Medicine,1 Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan2

Received 27 March 2002/ Returned for modification 16 May 2002/ Accepted 31 July 2002

Shiga toxin (Stx)-producing Escherichia coli (STEC) colonizes the human intestinal mucosa, produces Stx from phage, and causes the development of hemolytic-uremic syndrome via Stx-induced inflammatory cytokine production. Azithromycin exhibited strong in vitro activity against STEC without inducing Stx-converting phage, in marked contrast to norfloxacin. Azithromycin decreased the tumor necrosis factor alpha (TNF-{alpha}), interleukin-1ß (IL-1ß), and IL-6 production from Stx-treated human peripheral mononuclear cells or monocytes to a greater extent than did clarithromycin. In Stx-injected mice, azithromycin significantly suppressed Stx-induced TNF-{alpha}, IL-1ß, and IL-6 levels in serum and improved the outcome as assessed by survival rate. In the STEC oral infection experiment using immature mice immediately after weaning (weaned immature-mouse model), all mice died within 7 days postinfection. Azithromycin administration gave the mice 100% protection from killing, while ciprofloxacin administration gave them 67% protection. The data suggest that azithromycin (at least at higher concentrations) has a strong effect on Stx production by STEC and on the Stx-induced inflammatory host response and prevents death in mice. Azithromycin may have a beneficial effect on STEC-associated disease.


* Corresponding author. Mailing address: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibanchou, Asahimachidori, Niigata, Japan. Phone: 81-25-227-2050. Fax: 81-25-227-0762. E-mail: tatsuoy{at}med.niigata-u.ac.jp.


Antimicrobial Agents and Chemotherapy, November 2002, p. 3478-3483, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3478-3483.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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