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Antimicrobial Agents and Chemotherapy, March 2004, p. 747-752, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.747-752.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Antibiotic Susceptibility of Tropheryma whipplei in MRC5 Cells

Areen Boulos, Jean-Marc Rolain, and Didier Raoult*

Unité des Rickettsies, CNRS UMR 6020, IFR48, Faculté de Médecine, Université de la Méditerranée, 13385 Marseille Cedex 05, France

Received 1 July 2003/ Returned for modification 18 September 2003/ Accepted 7 November 2003

Whipple's disease is considered a rare chronic disease with a broad spectrum of clinical manifestations. Several antibiotics have been used for the treatment of this disease, and the current reference treatment was determined empirically on the basis of only a few clinical observations. Patients should be treated for months, and many relapse after antibiotic withdrawal. We report here the first extensive study on the susceptibilities of three reference strains of Tropheryma whipplei to antibiotic in cell culture by using a real-time PCR assay as previously described. We found that doxycycline, macrolides, ketolides, aminoglygosides, penicillin, rifampin, teicoplanin, chloramphenicol, and trimethoprim-sulfamethoxazole were active, with MICs ranging from 0.25 to 2 µg/ml. Vancomycin was somewhat active at an MIC of 10 µg/ml. We found heterogeneity in the susceptibility to imipenem, with one strain being susceptible and the two other strains being resistant. Cephalosporins, colimycine, aztreonam, and fluoroquinolones were not active. We also demonstrated that a combination of doxycycline and hydroxychloroquine was bactericidal. This combination has been shown to be active in the treatment of patients suffering from chronic infections with Coxiella burnetii, a bacterium that is also found intracellularly in acidic vacuoles. We believe, then, that this combination therapy should be further evaluated in clinical trials for the treatment of Whipple's disease.

* Corresponding author. Mailing address: Unité des Rickettsies, CNRS UMR 6020, IFR48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France. Phone: (33) 4-91-38-55-17. Fax: (33) 4-91-83-03-90. E-mail: Didier.Raoult{at}medecine.univ-mrs.fr.

Antimicrobial Agents and Chemotherapy, March 2004, p. 747-752, Vol. 48, No. 3
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.3.747-752.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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