Procena uticaja rezistencije na antibiotike i CYP450 polimorfizma na efikasnost eradikacije Helicobacter pylori infekcije

Abstract

Uvod: S obzirom da je bakterija Helicobacter pylori (H. pylori) prepoznata kao karcinogen I reda neophodno je adekvatno lečenje infekcije. Cilj našeg istraživanja bio je utvrđivanje učestalosti H. pylori infekcije, stope rezistencije na antibiotike i prisustvo i odnos potencijalnih prediktora uspeha lečenja. Metodologija: U prospektivnoj intervencionoj studiji je obuhvaćeno 415 bolesnika, od kojih su 180 bili H. pylori pozitivni. Svim H.pylori pozitivnim bolesnicima je urađena gornja endoskopija uz uzimanje biopsija sluznice radi određivanja antibiotske rezistencije, primenom PCR tehnike. Na osnovu rezultata rezistencije bolesnici su dobijali tailored made terapiju. Ispitivano je postojanje polimorfizma gena, tačkastih mutacija i kolonizacija gljivicom iz roda Candida. Rezultati: Prevalenca H. pylori infekcije iznosila je 43%. H. pylori pozitivni bolesnici su više živeli na selu (p<0.01), imali viši nivo CRP-a (p<0.01), niži nivo gvožđa (p<0.01), feritina (p<0.01) i češće atrofični gastritis (p=0.01). Ukupna stopa izlečenja iznosila je 86%, kod „naïve“ 93%, a u drugoj liniji terapije 83%. Najčešći terapijski režimi u prvoj liniji bila su četvorostruka terapija sa i bez bizmuta (79%). U drugoj liniji terapije, najčešće su propisivani trojna terapija bazirana na levofloksacinu i Pylera® (84%). Stopa rezistencije na klaritromicin iznosila je 55%, a rezistencija na fluorohinolone bila je 50%. Većina H. pylori pozitivnih bolesnika bili su heterozigoti za polimorfizam gena CYP450 (82%). Candida je izolovana kod 9% ispitivanih. Zaključci: Prevalenca H. pylori je visoka. Ukupna stopa izlečenja dala je zadovoljavajuće rezultate. Izbor terapije, visoka stopa antibiotske rezistencije, CYP450 polimorfizam, komplijansa bolesnika, prisustvo Candide neki su od faktora koji mogu remetiti uspeh terapije.

Introduction: Given that the bacterium Helicobacter pylori (H. pylori) is recognized as a carcinogen of the first order, adequate treatment of the infection is necessary. The aim of our research was to determine the frequency of H. pylori infection, the rate of antibiotic resistance and the presence and relationship of potential predictors of treatment success. Methodology: The prospective interventional study included 415 patients, of which 180 were H. pylori positive. All H. pylori positive patients underwent an upper endoscopy with mucosal biopsies to determine antibiotic resistance, using the PCR technique. Based on the results of resistance, the patients received tailored therapy. The existence of gene polymorphism, point mutations and colonization by Candida fungi were examined. Results: The prevalence of H. pylori infection was 43%. H. pylori positive patients lived more in the countryside (p<0.01), had higher levels of CRP (p<0.01), lower levels of iron (p<0.01), ferritin (p<0.01) and were more often diagnosed with atrophic gastritis (p=0.01 ). The overall cure rate was 86%, 93% in the "naïve" group, and 83% in the second line of therapy. The most common first-line treatment regimens were quadruple therapy with and without bismuth (79%). In the second line of therapy, triple therapy based on levofloxacin and Pylera® were the most often prescribed regimen (84%). The rate of resistance to clarithromycin was 55%, and resistance to fluoroquinolones was 50%. The majority of H. pylori positive patients were heterozygotes for the CYP450 gene polymorphism (82%). Candida was isolated in 9% of the examined. Conclusion: The prevalence of H. pylori is high. The overall eradication rate gave satisfactory results. Choice of therapy, high rate of antibiotic resistance, CYP450 polimorfizam, patient compliance, presence of Candida are some of the factors that can affect the success of therapy.