Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei

Florence Fenollar1, Jean-Marc Rolain, Laurent Alric

  • 1Université de la Méditerranée, Unité des Rickettsies, URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille cedex 05, France.

Insights

Whipple's disease treatment with trimethoprim/sulfamethoxazole can fail due to Tropheryma whipplei resistance. Sequencing the folP gene can identify mutations predicting treatment failure, guiding better therapeutic choices.

Area of Science:

  • Infectious Diseases
  • Microbiology
  • Genetics

Background:

  • Whipple's disease (WD) is a chronic bacterial infection caused by Tropheryma whipplei.
  • Standard treatment involves a 1-year course of oral trimethoprim/sulfamethoxazole (SXT).

Observation:

  • Tropheryma whipplei exhibits resistance to trimethoprim, a component of SXT.
  • Mutations in the folP gene, encoding the target of sulfonamides, are linked to SXT resistance.
  • Three new patients developed acquired resistance to SXT during WD treatment, with one experiencing biological failure.

Findings:

  • Analysis of 62 folP sequences from 59 WD patients revealed specific amino acid changes.
  • Two mutations, N4S and S234F at key positions, significantly predicted secondary sulfamethoxazole failure in four out of five cases.

Implications:

  • folP gene sequencing at diagnosis can identify patients at risk of SXT failure.
  • Detecting these mutations may help avoid sulfamethoxazole monotherapy and guide alternative treatment strategies.
  • This approach can improve treatment outcomes for Whipple's disease by personalizing antibiotic selection.

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