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Antimicrobial Agents and Chemotherapy, May 2005, p. 1787-1793, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1787-1793.2005

Bactericidal Activity of First-Choice Antibiotics against Gamma Interferon-Induced Persistent Infection of Human Epithelial Cells by Chlamydia trachomatis

Nathalie Reveneau, Deborah D. Crane, Elizabeth Fischer, and Harlan D. Caldwell*

Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840

Received 30 July 2004/ Returned for modification 25 October 2004/ Accepted 20 January 2005

Chlamydia trachomatis is responsible for clinically important chronic inflammatory diseases of humans, including trachoma and pelvic inflammatory disease. Persistent infection of mucosal sites may contribute to the development of these chronic inflammatory diseases. Standard clinical therapy results in satisfactory cure rates of acute infections; however, chronic infection associated with persistence has been suggested to be less responsive to antibiotic therapy. We report the efficiency of two first-line chlamydial antibiotics, azithromycin and doxycycline, under conditions of eradication of C. trachomatis persistent infection using the in vitro model of gamma interferon (IFN-{gamma})-mediated persistence and reactivation from persistence. Doxycycline was superior in eradicating acute (minimal bactericidal concentration [MBC]100 = 2.5 to 5.0 µg/ml) compared to persistent (MBC100 = 10 to 50 µg/ml) infection. In contrast, azithromycin was significantly more effective in eradicating persistent infection (MBC100 = 2.5 to 5.0 µg/ml) than acute infection (MBC100 = 10 to 50 µg/ml). The superior bactericidal effect of azithromycin against persistent infection was found to correlate with the enhanced uptake of the drug by IFN-{gamma}-treated infected epithelial cells. Based on these findings, we hypothesize that azithromycin should be a particularly efficacious anti-infective agent for the eradication of IFN-{gamma}-induced chlamydial persistent infection in vivo.

* Corresponding author. Mailing address: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, 903 South 4th St., National Institutes of Health, Hamilton, MT 59840. Phone: (406) 363-9333. Fax: (406) 363-9380. E-mail: hcaldwell{at}niaid.nih.gov.

Antimicrobial Agents and Chemotherapy, May 2005, p. 1787-1793, Vol. 49, No. 5
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.5.1787-1793.2005




This article has been cited by other articles:

  • Horner, P (2006). The case for further treatment studies of uncomplicated genital Chlamydia trachomatis infection.. Sex. Transm. Infect. 82: 340-343 [Abstract] [Full Text]  


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