Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection

摘要

AIM: To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug outpumping during Helicobacter pylori ( H pylori) infection treatment with classic antibiotic therapy. METHODS: Pgp activity was determined in gastric mucosa biopsy specimens obtained from 53 patients with pathohistologically verified gastritis and microbiologically confirmed H pylori infection, and compared with the Pgp activity in 12 control subjects with normal endoscopic findings. TheH pylori positive patients were treated with short-term 7-d therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor. Pgp activity was determined by flow cytometry in the test of rhodamine dye efflux and quantified as mean fluorescence ratio (RMF).RESULTS: Upon the first cycle,H pylori was successfully eradicated in 20 patients, whereas therapy was continued in 33 patients. In the course of antibiotic therapy, RMF increased (P＜0.05) and gastric cells showed higher rhodamine dye efflux. The mean pre-treatment RMF values were also higher (P＜0.0001) in patients with multiple therapeutic failure than in those with successful H pylorieradication and control subjects.CONCLUSION: Pgp might be one of the causes of therapy failure in patients with H pylori and antibiotic therapy could be chosen and followed up on the basis of the Pgp transporter local activity.