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J Antimicrob Chemother. 2010 Sep;65(9):2005-12. doi: 10.1093/jac/dkq263. Epub 2010 Jul 17.

Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease.

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  • 1Université de la Méditerranée, Unité des Rickettsies, URMITE CNRS-IRD UMR 6236, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France.

Abstract

OBJECTIVES:

Classic Whipple's disease is a chronic disease caused by Tropheryma whipplei. A recent study reported that intravenous treatment with ceftriaxone or meropenem followed by a 1 year treatment with trimethoprim/sulfamethoxazole cured all patients. However, we have previously reported that T. whipplei is poorly susceptible to beta-lactams and resistant to trimethoprim. Herein, we want to evaluate these antibiotic regimens.

PATIENTS AND METHODS:

Since the organism was first cultured in Unité des Rickettsies, Marseille (France), we received samples for the diagnosis of T. whipplei infections. Among the 37 patients referred to us for management, 24 patients presented classic Whipple's disease. Among them, 14 patients treated with trimethoprim/sulfamethoxazole were followed up for >3 years.

RESULTS:

None of the 14 patients was cured. One patient presented with an adverse side effect necessitating treatment cessation. Two patients developed an immune reconstitution inflammatory syndrome. One patient died 4 weeks after initiation of the treatment. Five patients developed clinical resistance; four of these having mutations on the target gene of sulfamethoxazole (folP). Five patients developed a relapse after cessation of trimethoprim/sulfamethoxazole after an average of 30 months. The high relapse rate may be linked to our recruitment. However, discrepancies with other centres could be due to the heterogeneity of diagnosis and cure criteria, different follow-up methods or infections due to T. whipplei strains with better susceptibility to antibiotics.

CONCLUSIONS:

We confirmed, as predicted from prior testing of T. whipplei susceptibility, that trimethoprim/sulfamethoxazole is not optimal for classic Whipple's disease. In addition, 1 year treatment may be followed by relapses.

PMID:
20639526
[PubMed - indexed for MEDLINE]
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