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Стандартный 7 дневный режим лечения helicobacter

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Those who were lost to follow up, or used antibiotics in the time period between the end of therapy and post-treatment urea breath test, or could not complete the treatment course because of severe side effects, were excluded in the per-protocol analysis.


Statistical analysis

The study was a three-armed randomized clinical trial with groups A, B and C including 110, 113 and 112 patients for the final statistical analysis (per-protocol analysis). In addition, intention-to-treat analysis was also performed. Chi-square test was used to compare the eradication rates by intention-to-treat as well as per-protocol analyses in the three groups. P < 0.05 was considered statistically significant.



Five patients in group A, 3 in group B, and 4 in group C were lost to follow up. Four patients in group A, 2 in group B, and 4 in group C used antibiotics in the time period between the end of therapy and post-treatment urea breath test. One patient in group A and 2 in group B discontinued the regimen due to severe allergic reactions. Minor side effects were experienced by 6 patients in group A (vomiting, skin rash and abdominal pain), 5 patients in group B (vomiting, skin rash and pruritis) and 12 patients in group C (vomiting, diarrhea, headache, skin rash and abdominal pain).

    Demographic and clinical details of the patients remaining in the three groups are shown in Table 1. The per-protocol eradication rate was 91.81% (101 patients from a total of 110) in group A, 85.84% (97 patients from a total of 113) in group B, and 92.85% (104 patients from a total of 112) in group C. The intention-to-treat eradication rate was 84.17% in group A, 80.83% in group B, and 86.67% in group C. The new protocol yielded the highest eradication rates by both per-protocol and intention-to-treat analyses followed by the standard triple and quadruple regimens, respectively. However, the differences were not statistically significant between the three groups. They were also not significantly different in the occurrence of minor side effects, either.


Table 1  Demographic and clinical data of patients who completed the treatment



We opted to prescribe antibiotics for ten days because 4- and 7-d regimens have been unsuccessful in Iran[9]. In this study, the eradication rates for the triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies were not significantly different. Occurrence of serious side effects necessitating termination of therapy was negligible in all three groups. Minor side effects were well tolerated among all three groups and occurred infrequently with almost the same frequency. Diarrhea and headache occurred in group C only, but other side effects were experienced in all groups.

    Some recent studies have compared the efficacy of triple versus quadruple therapy, and a recent meta-analysis has assessed these studies[10]. Eradication rates were not significantly different among patients receiving triple or quadruple therapy. The duration of therapy (7 vs 10 d) did not significantly change the results, either. Triple therapy given for a 10-d period achieved an intention-to-treat eradication rate of 79% compared with 77% for a 7-d period. Quadruple therapy on the other hand gave an intention-to-treat eradication rate of 83% for a 10-d period and 80% for a 7-d period[10]. The eradication rates by intention-to-treat analysis among patients receiving either triple or quadruple therapy in this study were almost similar to those obtained previously[4,10,11].

    A previous preliminary study by the authors using ampicillin-sulbactam instead of amoxicillin in 10-d standard quadruple therapy on 26 patients has yielded a 92% eradication rate by per-protocol analysis which was well tolerated among patients (unpublished data). The present study is the first randomized clinical trial to evaluate the efficacy of the new protocol and to compare it with standard triple and quadruple therapies in a relatively large number of patients. Although not statistically significant, the new protocol seems to be more effective than traditional protocols.

    H pylori infection has a high prevalence rate of about 90% in Iran, which emphasizes the importance of having an effective regimen to eradicate H pylori[12]. The metronidazole-based standard triple therapy regimen has been unsuccessful in H pylori eradication, yielding an eradication rate of only about 55% compared with about 90% in other countries[13,14]. This is because metronidazole-resistant H pylori strains are rather common in Iran as well as in other developing countries[9,15]. The high prevalence of metronidazole-resistance in Iran could be explained by the frequent use of metronidazole to treat various infections, thereby promoting antibiotic resistance in H pylori.

    On the other hand, 7.4% of H pylori isolates in Iran have been reported to be resistant against amoxicillin and higher resistance rates of up to 29% have been reported in other developing countries[15,16]. Therefore, the use of ampicillin-sulbactam instead of amoxicillin in the quadruple therapy regimen, leading to an eradication rate of 92.85% by per-protocol and 86.67% by intention-to-treat analysis in this study, may be useful against metronidazole- and amoxicillin-resistant H pylori strains in developing countries like Iran. Consequently, there would be no need to exclude metronidazole (because of antibiotic resistance), which is an inexpensive and widely available anti-H pylori agent in developing countries.

    Since the present study did not show the effectiveness of the new combination on ampicillin-resistant strains, we should bear in mind that some of the resistant strains do not act through beta-lactamase but rather penicillin binding proteins (PBPs)[17]. Perhaps in vitro study of ampicillin-resistant strains using ampicillin-sulbactam combination can help answer whether the combination is effective against the resistant strains.

    In conclusion, the results of this study provide further support for the equivalence of triple and amoxicillin-based quadruple therapies in terms of effectiveness, compliance and side-effect profile when administered as a first-line treatment for H pylori infection. Moreover, the new protocol using ampicillin-sulbactam instead of amoxicillin in the quadruple regimen is a suitable first-line alternative to be used in regions with amoxicillin-resistant H pylori strains.



The authors thank Bayat A, PhD for providing sultamicillin.



1    Dore MP, Osato MS, Realdi G, Mura I, Graham DY, Sepulveda AR. Amoxycillin tolerance in Helicobacter pylori. J Antimicrob Chemother 1999; 43: 47-54  PubMed

2    Wu H, Shi XD, Wang HT, Liu JX. Resistance of helicobacter pylori to metronidazole, tetracycline and amoxycillin. J Antimicrob Chemother 2000; 46: 121-123  PubMed

3    Crone J, Granditsch G, Huber WD, Binder C, Innerhofer A, Amann G, Hirschl AM. Helicobacter pylori in children and adolescents: increase of primary clarithromycin resistance, 1997-2000. J Pediatr Gastroenterol Nutr 2003; 36: 368-371  PubMed

4    McLoughlin RM, O‘Morain CA, O‘Connor HJ. Eradication of Helicobacter pylori: recent advances in treatment. Fundam Clin Pharmacol 2005; 19: 421-427  PubMed

5    Horii T, Mase K, Suzuki Y, Kimura T, Ohta M, Maekawa M, Kanno T, Kobayashi M

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