Whipple’s disease is a chronic infection caused by the actinomycete Tropheryma whipplei. We conducted a randomized controlled trial of the efficacy
of antimicrobials that are able to cross the blood-brain barrier and to which T whipplei is susceptible. This was a randomizedcontrolled trial to show that treatment with ceftriaxone or meropenem, followed by trimethoprim–sulfamethoxazole, cures patients with Whipple’s disease. One asymptomatic individual with infection of the cerebrospinal fluid required additional therapy.
1. The first patient was admitted to the trial in January 1999. The 42nd patient completed the scheduled follow-up time of 36 months in July 2006. During this time, 61 patients with presumed Whipple’s disease were evaluated for eligibility. Eighteen patients were excluded because they had received antibiotic therapy for Whipple’s disease in the past or recently had been treated with antibiotics for a period longer than 4 weeks. One patient/physician did not give consent. Thus, 42 patients with the provisional diagnosis of untreated Whipple’s disease were available for randomization.
2. Twenty-one patients were randomized to receive ceftriaxone and 21 patients were randomized to meropenem (Figure 1). In 2 patients, one assigned to ceftriaxone and the other assigned to meropenem, tissue diagnosis was not confirmed by the histopathologist. Therefore, 20 patients with untreated Whipple’s disease (as defined in the protocol) were studied in each treatment group. On average, 8 patients with untreated Whipple’s disease were enrolled per year from Germany and Austria. One patient was recruited from Switzerland and another was recruited from France. In one patient with T whipplei endocarditis, tissue diagnosis was made by electron microscopy in the excised aortic valve;29 all other patients presented with subtype 1 macrophages in the biopsy.
3. There were no significant differences in baseline characteristics (Tables 1 and 2)
This study showed that randomized controlled trials can be performed in very rare disorders, albeit at the expense of some test stringency. This trial in Whipple’s disease was not powered to detect a difference in efficacy between ceftriaxone and meropenem. Both antimicrobials were highly efficacious. Ceftriaxone, however, is less costly and requires only one daily infusion.