Efficacy of ceftriaxone or meropenem as initial therapies in Whipple's disease

Gastroenterology. 2010 Feb;138(2):478-86; quiz 11-2. doi: 10.1053/j.gastro.2009.10.041. Epub 2009 Oct 29.

Abstract

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 x 2 g, 20 patients) or meropenem (3 x 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.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Biopsy
  • Ceftriaxone / administration & dosage
  • Ceftriaxone / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Injections, Intravenous
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / pathology
  • Male
  • Meropenem
  • Middle Aged
  • Remission Induction
  • Thienamycins / administration & dosage
  • Thienamycins / therapeutic use*
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*
  • Tropheryma
  • Whipple Disease / drug therapy*
  • Whipple Disease / pathology

Substances

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