Increased activity of Pgp multidrug transporter in patients with Helicobacter pylori infection.
OBJECTIVE
To determine whether local antibiotic resistance involves P-glycoprotein (Pgp)-mediated active drug out-pumping 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. The H 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 pylori eradication and control subjects.


CONCLUSIONS
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.
Babic
Zarko
Z
Department of Gastroenterology, University Department of Medicine, Sveti Duh General Hospital, Fabkovieva 3, Zagreb HR-10000, Croatia. zarko.babic@zg.hinet.hr
Svoboda-Beusan
Ivna
I
Kucisec-Tepes
Nastja
N
Dekaris
Dragan
D
Troskot
Rosana
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000502:physiology; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism*; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008875:Middle Aged
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D000658:Amoxicillin; D017963:Azithromycin