title: Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Université de la Méditerranée, Unité des Rickettsies, URMITE CNRS-IRD UMR 6236, Faculté de Médecine, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lagier
authors.forename: Florence
authors.initials: F
authors.lastname: Fenollar
authors.forename: Hubert
authors.initials: H
authors.lastname: Lepidi
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D054851:Tropheryma / Q000187:drug effects / Q000302:isolation & purification*; D008061:Whipple Disease / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination