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Jean-Christophe Lagier, Florence Fenollar, Hubert Lepidi, Didier Raoult, Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease, Journal of Antimicrobial Chemotherapy, Volume 65, Issue 9, September 2010, Pages 2005–2012, https://doi.org/10.1093/jac/dkq263
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Abstract
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 β-lactams and resistant to trimethoprim. Herein, we want to evaluate these antibiotic regimens.
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.
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.
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.