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

摘要

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.Trial registration: ISRCTN45658456. ? 2013 The British Infection Association.