Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease

Background & Aims

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.

Methods

Patients from central Europe with previously untreated Whipple's disease (n = 40) were assigned randomly to groups given daily infusions of either ceftriaxone (1 × 2 g, 20 patients) or meropenem (3 × 1 g, 20 patients) for 14 days, followed by oral trimethoprim–sulfamethoxazole for 12 months. The primary outcome measured was maintenance of remission for 3 years, determined by a composite index of clinical and laboratory data as well as histology.

Results

All patients were observed for the entire follow-up period (median, 89 mo; range, 71–128 mo); all achieved clinical and laboratory remission. Remission was maintained in all patients during the time of observation, except for 2 who died from unrelated causes. A single patient with asymptomatic cerebrospinal infection who was resistant to both treatments responded to chloroquine and minocycline. The odds ratio for the end point (remission for at least 3 years) was 0.95 (95% confidence interval, 0.05–16.29; P = 1.0).

Conclusions

This was a randomized controlled 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.

Abbreviations used in this paper: MIC, minimum inhibitory concentration, PAS, periodic acid–Schiff, PCR, polymerase chain reaction