engleski

Increased multidrug transporter Pgp activity in patients with Helicobacter pylori infection

Etiological ; cause of peptic ulcer disease is Helicobacter pylori (HP). In treatment the use of 5-nitroimidazoles, macrolides and beta-lactams are common. The antibiotic therapy is cause for resistance of etiological agent. In macrolides and beta-lactams the mechanisms of resistance is well understandable, while in 5-nitroimidazole is still unknown. Problems are connected to kind of test and definition of resistance, as well as the accuracy of the test. Frequency of resistance depends on total antibiotic use in clinical practice, not only in HP treatment.Human gastrointestinal cells overexpress multidrug tranmsporter P-glycoprotein (Pgp), a transmembrane protein known to confer resistance by pumping a wide range of drugs out of the cell, by using energy from ATP. The aim of the study was to determine whether the local resistance depends on active extrusion of antibiotics from gastric cell by Pgp. Study population consisted of 53 patients with endoscopically determined antral gastritis who had presence of HP infection, and 12 patients with normal upper endoscopical finding without HP infection. HP infection was confirmed in these 53 cases by isolation and typisation and the sensitivity was determined by E test (AB-biodisk) and Chave's method (1999), but also by histology (Giemsa). At the beginning of the study all HP positive patients were treated with classical short triple therapy containing PPI (pantoprazole) and 2 antibiotics [amoxicilin (AMX) and metronidazole (MET) or clarithromycin (CLAR) or azitromycin (AZT) in combination]. The Pgp activity was measured in gastric biopsy samples by flow cytometry using the rhodamine efflux (RE) test. Using the fluorescent rhodamine dye and the cyclosporine it is possible to distinguish resistant samples from sensitive samples. Test controls were K562 cells. Thirty-three patients had multiple therapy failures. Patients with one or more therapy failures show higher RE in comparison to HP eradicated ones and controls (p<0.000001). For determining drug resistance sensitivity of RE was 90.90%, specificity 71.787% and accuracy 81.54 % at the threshold value of 1.0 RE. Our results indicate that Pgp activity measured by the method of rhodamine efflux in patients with HP infection could serve to discover resistant phenotype and to monitor the therapy outcome.

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