| Objective:With the rising rates of drug resistance, the eradication rate ofHelicobacter pylori(H.pylori) is getting lower and lower. Against thisbackground, both the international latest Maastricht Ⅳ/Florence ConsensusReport and The fourth national Helicobacter pylori infection consensus reportall recommended bismuth-based quadruple therapies as the first-line treatmentfor H.pylori eradication. Antibiotic resistance is the main reason for the failureof H.pylori eradication.The purpose of this study is to know about the drugresistance rates of metronidazole, clarithromycin, amoxicillin, levofloxacin,furazolidone, tetracycline and to provide the clinical guidelines for H.pylorieradication. At the same time, this study intends to evaluate the efficacy andsafety of different bismuth-based quadruple therapies for the eradication ofH.pylori in this region, and to study the correlation of clinical eradication rateand drug resistance，and to provide reference for choosing reasonable andeffective solution for H.pylori eradication.Methods：1Research on the drug resistance of H.pylori: A total of260H.pylori-infected patients who met the requirements were enrolled and gastricmucosa tissues of the260patients were sampled to isolate and identifyH.pylori.Kirby-Bauer test was performed to test the susceptibility of H.pyloriclinical isolates to metronidazole, clarithromycin, amoxicillin, levofloxacin,furanzolidone and tetracycline.2Clinical research:A total of260H.pylori-infected patients who met therequirements were enrolled and randomly divided into four groups. Eachgroup was randomly treated with one of the A, B, C, D regimen, and named asgroup A, group B, group C and group D. Group A was treated with Bismuth potassium citrate (220mg, bid), Esomeprazole (20mg, bid), Amoxicillin(1000mg, bid), Clarithromycin (500mg, bid), group B was treated withBismuth potassium citrate (220mg, bid), Esomeprazole (20mg, bid),Amoxicillin (1000mg, bid), Levofloxacin (200mg, bid), group C was treatedwith Bismuth potassium citrate (220mg, bid), Esomeprazole (20mg, bid),Amoxicillin (1000mg, bid), Furanzolidone (100mg, bid), and group D wastreated with Bismuth potassium citrate (220mg, bid), Esomeprazole (20mg,bid), Amoxicillin (1000mg, bid), Metronidazole (400mg, bid).The treatmentlasted10days in all groups. Esomeprazole and Bismuth potassium citratewere taken half an hour before meals, antibiotics in each groups were takenimmediately after meals. After the eradication of H.pylori, duodenal ulcerpatients continued to give esomeprazole20mg qd, gefarnate100mg tid orallyfour weeks, gastric ulcer patients continued to give esomeprazole20mg qd,gefarnate100mg tid orally six weeks. At least four weeks after the end oftreatment, H.pylori eradication was assessed by13C-urea breath test or14C-urea breath test, and the the adverse events in each group were observedand recorded during the treatment.Results:1The comparison of patient’s general information between the fourgroups: There were no statistical significance in age, sex, disease classification,smoking and drinking between the four groups(P>0.05).2The results of H.pylori cultivation: A total of155H.pylori strains wereisolated from260samples, the positive rate is59.6%. The positive rate ofH.pylori cultivation was61.6%in the male patients and the positive rate was57.0%in the female patients. The positive rates of H.pylori cultivation ingroup A, B, C and D were53.8%,64.6%,55.4%and64.6%, respectively.There were no statistical significance in the positive rate between different sexand groups(P>0.05).3The results of susceptibility testing：In the155cases of H.pylori culturepositive specimens， the resistance rate of H.pylori to metronidazole,clarithromycin, amoxicillin, levofloxacin, furanzolidone and tetracycline was 94.2%,21.3%,2.6%,5.8%,1.9%and3.2%, respectively. The dual resistantrate of clarithromycin and metronidazole was20.6%, the dual resistance rateof metronidazole and amoxicillin was2.6%, the dual resistance rate ofmetronidazole and levofloxacin was4.5%, the dual resistance rate ofmetronidazole and furazolidone was1.9%, the dual resistance rate ofmetronidazole and tetracycline was3.2%, the triple resistance rate ofmetronidazole，clarithromycin and levofloxacin was1.3%.4The drug-resistant spectrum of different diseases: In the155patients ofH.pylori culture positive, patients with chronic gastritis had116, patients withpeptic ulcer had39. In the116patients with chronic gastritis, the resistancerate of H.pylori to metronidazole, clarithromycin, amoxicillin, levofloxacin,furanzolidone and tetracycline was93.1%,24.1%,2.6%,6.9%,2.6%and1.7%, respectively. In the39patients with peptic ulcer, the resistance rate ofH.pylori to metronidazole, clarithromycin, amoxicillin, levofloxacin,furanzolidone and tetracycline was97.4%,12.8%,2.6%,2.6%,0and7.7%,respectively. Comparing different diseases, the resistance rates of6kinds ofantibiotic have no significant differences(P>0.05). This suggests that the typeof diseases and antibiotic resistance of H.pylori have no significantrelationship.5The comparison of H.pylori eradication rate：63patients completed thetreatment and2patients were lost to follow-up in group A.53patients weresuccessfully eradicated and10patients failed to eradicate.64patientscompleted the treatment and1patient was lost to follow-up in group B.59patients were successfully eradicated and5patients failed to eradicate.64patients completed the treatment and1patient was lost to follow-up in groupC.61patients were successful eradicated and3patients failed to eradicate.62patients completed the treatment and3patients were lost to follow-up in groupD.49patients were successfully eradicated and13patients failed to eradicate.The rate of H.pylori eradication in group A, B, C and D was81.5%,90.8%,93.8%and75.4%respectively by intention to treat(ITT)analysis, was84.1%,92.2%,95.3%and79.0%respectively by per protocol(PP)analysis. The differences had statistical significance in the rate of H.pylori eradicationamong the four groups both by ITT and PP analysis(P<0.05).There werestatistical difference between group A and C, group C and D, group B and Dboth by ITT and PP analysis(P<0.05). Either ITT or PP analysis, no statisticalsignificance were found between group A and B, group A and D, group B andC(P＞0.05).6The comparison of adverse reactions between different solutions: In thefour groups, there were3cases,5cases,4cases and6cases occurred adversereactions. The adverse reactions rate of the four groups was4.8%,7.8%,6.2%and9.7%, respectively. The rate of adverse reactions in the four groupsshowed no statistical difference(P>0.05). The main adverse reactions werenausea, abdominal pain, diarrhea, dizziness, headache, oral odor, andorange-red urine, and so on. The adverse reactions can be tolerated by allpatients, the symptoms disappear on their own after drug withdrawal, noserious adverse reactions occurred in the process of treatment.7The impact of antibiotic resistance on the eradication rates of H.pylori:In the35patients of H.pylori culture positive in group A,28patients weresensitive to clarithromycin and26patients were succeed to eradicate.7patients were resistant to clarithromycin and5patients were succeed toeradicate. The eradication rate of H.pylori between sensitive and resistantpatients showed no statistical difference(P>0.05). In the42patients ofH.pylori culture positive in group B,40patients were sensitive to levofloxacinand38patients were succeed to eradicate.2patients were resistant tolevofloxacin and the2patients were all succeed to eradicate. The eradicationrate of H.pylori between sensitive and resistant patients showed no statisticaldifference(P>0.05). In the36patients of H.pylori culture positive in group C,34patients were sensitive to furanzolidone and the34patients were allsucceed to eradicate.2patients were resistant to furanzolidone and the2patients were all succeed to eradicate. In the42patients of H.pylori culturepositive in group D,2patients were sensitive to metronidazole and the2patients were all succeed to eradicate.40patients were resistant to metronidazole and31patients were succeed to eradicate.The eradication rateof H.pylori between sensitive and resistant patients showed no statisticaldifference(P>0.05).Conclusion:1In Hebei province, the resistance rate of H.pylori to metronidazole andclarithromycin is higher, which should not be used as first-line agent forH.pylori treatment. The resistance rate of H.pylori to amoxicillin, levofloxacin,furanzolidone and tetracycline is lower, which can be used first for H.pyloritreatment.2In Hebei province, bismuth-based quadruple therapies can overcomethe antibiotic resistance of H.pylori. The bismuth-furanzolidone-containingquadruple therapy and the bismuth-levofloxacin-containing quadruple therapyhave higher eradication rate and have higher safety, which can be used as thefirst-line regimen for H.pylori eradication. |
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