Resistance to trimethoprim/sulphamethoxazole and

Florence Fenollar (1) , Jean-Marc Rolain (1) , Laurent Alric (2) , Thomas Papo (3) , Marie-Paule Chauveheid (1) , Diederik van de Beek (4) , Didier Raoult (1)

1 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
2 Department of Internal Medicine
3 Department of Internal Medicine
4 Department of Neurology

Whipple's disease (WD) is a chronic infection caused by . A 1-year treatment of oral trimethoprim/sulphamethoxazole (SXT) is commonly used. Advances in the culture of has allowed for full genome sequencing and antibiotic susceptibility testing, which has demonstrated resistance of to trimethoprim. Several mutations in the gene that encodes dihydropteroate synthase, the target of sulphonamides, has been reported for one patient with clinically acquired resistance to SXT. Here we report three new patients who experienced clinically acquired resistance to SXT during treatment and one patient with biological failure. Sixty-two sequences from DNA samples of 59 WD patients were also obtained. Among the detected amino acid changes, two positions (N4S and S234F) significantly predicted secondary sulphamethoxazole failure (four of five). We suggest that these mutations should be detected at the time of WD diagnosis by sequencing in order to avoid sulphamethoxazole monotherapy.

Mots clés: Whipple's disease; Trimethoprim/sulphamethoxazole; Sulfadiazine; Antibiotic resistance

Florence Fenollar, Jean-Marc Rolain, Laurent Alric, Thomas Papo, Marie-Paule Chauveheid, et al.. Resistance to trimethoprim/sulphamethoxazole and. International Journal of Antimicrobial Agents, 2009, 34 (3), pp.255. ⟨10.1016/j.ijantimicag.2009.02.014⟩. ⟨hal-00556334⟩