Intravenous ceftriaxone, followed by 12 or three months of oral treatment with trimethoprim-sulfamethoxazole in Whipple's disease

J Infect. 2013 Mar;66(3):263-70. doi: 10.1016/j.jinf.2012.12.004. Epub 2013 Jan 3.


Background: There is no agreement on how and for how long Whipple's disease should be treated. In a randomized trial it was shown that patients can be cured with ceftriaxone or meropenem followed by trimethoprim-sulfamethoxazole for 12 months. The present study tested whether trimethoprim-sulfamethoxazole for three months is sufficient.

Methods: In the time from July 2004 to July 2008, 40 untreated patients from central Europe were sequentially admitted to an open-label, non-randomized extension of the previous trial with essentially an identical protocol. The modified treatment consisted of 2 g ceftriaxone intravenously once daily for 14 days followed by oral trimethoprim-sulfamethoxazole 160/800 mg twice daily for 3 months. Primary endpoint was treatment efficacy compared with the previous study.

Results: Twelve months of treatment with trimethoprim-sulfamethoxazole was not more effective than 3 months as indicated by clinical findings, laboratory (p = 0.405, p = 0.631, resp.), and histological data (p = 0.456). 36 of 37 surviving patients including 14 with cerebrospinal infection were in remission without evidence of recurrence after a median follow-up time of 80 months. In one patient, Tropheryma whipplei arthritis recurred 63 months after initial therapy. Secondary endpoints indicate that histology of intestinal biopsies was a more useful indicator to determine eradication of T. whipplei than PCR. In submucosal and extra-intestinal tissue, the diagnostic value of the PCR was superior. Prospective data disclosed a heterogeneous spectrum of clinical presentation and course of Whipple's disease.

Conclusion: This study indicates that ceftriaxone followed by three months of trimethoprim-sulfamethoxazole is highly efficacious in the treatment of Whipple's disease.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Ceftriaxone / administration & dosage
  • Ceftriaxone / adverse effects
  • Ceftriaxone / therapeutic use*
  • Drug Therapy, Combination
  • Endoscopy
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*
  • Tropheryma / drug effects*
  • Whipple Disease / drug therapy*
  • Whipple Disease / pathology


  • Anti-Bacterial Agents
  • Ceftriaxone
  • Trimethoprim, Sulfamethoxazole Drug Combination

Associated data

  • ISRCTN/ISRCTN45658456