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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References

Background:

Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%).

Aim:

To evaluate the efficacy of a new short-term treatment sequence on H. pylori eradication.

Methods:

A total of 52 patients with H. pylori infection and either non-ulcer dyspepsia (34 patients) or peptic ulcer (18 patients) were enrolled to receive a 10-day therapy: omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, followed by omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for the remaining 5 days. H. pylori infection at entry was assessed by rapid urease test and histology on biopsies from the antrum and the corpus. Bacterial eradication was assessed by endoscopy (peptic ulcer patients) or 13C urea breath test (non-ulcer dyspepsia patients) 4–6 weeks after therapy had ended.

Results:

All patients completed the study. H. pylori eradication was achieved in all but one patient, with an eradication rate of 98% (95% CI: 94.3–100) with intention-to-treat analysis. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for 4 days instead of 5 days. No major side-effects were reported but three (6%) patients complained of mild side-effects.

Conclusions:

The use of this ‘five plus five’ therapy schedule as an initial treatment for H. pylori deserves further investigation.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References

Helicobacter pylori infection causes chronic active gastritis and peptic ulcer; its role in gastric carcinogenesis is also of current interest.1[2]–3 Several treatment regimens have been proposed to cure this infection, but no therapy leads to a 100% eradication rate.4 In 1996 a decision was made by the European H. pylori Study Group to put forward an effective standardized treatment to be followed throughout Europe.5 These guidelines suggest that a 1-week triple therapy consisting of a proton pump inhibitor, clarithromycin and either amoxycillin or tinidazole should be used as first choice in treating H. pylori infection.5 This milestone treatment regimen has offered a common line of thought and has been widely employed, even outside Europe. Nevertheless, there is increasing evidence that the results obtained are often disappointing (eradication rate < 80%) using these treatment regimens.6[7][8][9][10][11][12][13][14][15]–16 Moreover, bacterial eradication following a failed initial triple therapy is notoriously difficult to achieve and therefore certain caution should be taken when opting for the sequence of regimens used in H. pylori treatment.17[18]–19

Using a dual therapy followed by a triple therapy sequence, we previously obtained a very high H. pylori eradication rate (97% in 75 patients).20 Nervertheless, this therapeutic approach required the use of an initial 2-week dual therapy, followed by a washout of 4 weeks, to test patients for bacterial eradication and then further treatment with a 1-week triple therapy in the event of an eradication failure. Therefore, in the present study, we have attempted to simplify this highly effective treatment sequence, in order to reduce the duration of therapy and also to avoid the need for an assessment procedure after the initial course of treatment.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References

Patients complaining of dyspeptic symptoms, referred to our Endoscopic Service for upper gastrointestinal endoscopy, were considered for recruitment into the study. The demographic and clinical characteristics of these patients are reported in Table 1. Patients with liver cirrhosis, renal failure, alcoholics, those who were using NSAIDs, and those who had taken proton pump inhibitor, bismuth salts and/or antibiotic treatment in the previous 2 months were excluded from the study. H. pylori infection at entry was determined by rapid urease test and histological assessment. Rapid urease test (CP-test, Yamanuochi, Milan, Italy) was performed using two biopsy specimens (one each from the antrum and corpus). The histological assessment of H. pylori status was performed using a further four biopsy specimens (stained with Giemsa), two from the antrum and two from the gastric body. Patients were assigned to receive a 10-day treatment, including omeprazole 20 mg b.d. plus amoxycillin 1 g b.d. for the first 5 days, and omeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg b.d. for a further 5 days. Omeprazole was prescribed before breakfast and dinner, while all antibiotics were given after these meals. Patients with duodenal or gastric ulcer were given omeprazole (20 mg b.d.) for a total of 1 month. Each patient was asked to return at the end of antibiotic treatment for a clinical check-up and assessment of therapy compliance and side-effects by personal interview. Four to 6 weeks after concluding proton pump inhibitor therapy, H. pylori eradication was assessed by endoscopy in peptic ulcer patients and by a 13C urea breath test (Helicobacter test INFAI, Sofar, Milan, Italy) in non-ulcer dyspepsia patients. All patients gave their informed consent to participate.

Table 1.  . Baseline demographic and clinical characteristics Thumbnail image of

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References

All 52 patients completed the study. H. pylori infection was cured in 51 patients, and an eradication rate of 98% (95% CI: 94.3–100) at intention-to-treat analysis was obtained. Only one non-ulcer dyspepsia patient failed bacterial eradication using this initial treatment. At repeat endoscopy, peptic ulcer healing was observed in all patients. Patient compliance was good (consumption of prescribed drugs > 95%) for all but one patient, who took the triple therapy regimen for the first 4 days instead of the full 5 days, although bacterial eradication was nonetheless achieved. The treatment was well tolerated, and no major side-effects were reported. Only three (6%) patients complained of mild side-effects (one pruritus, one abdominal pain, and one metallic taste), and the treatment was not discontinued in any case. H. pylori eradication was achieved with the ranitidine bismuth citrate-based triple therapy in the patient who failed initial treatment; no side-effects were reported.

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References

The 1996 European guidelines had the important merit of deciding, once and for all, a standardized treatment suggesting the use of a 1-week triple therapy as first choice in treating H. pylori infection.5 Nevertheless, a recent meta-analysis found a fairly low eradication rate (82% in 3655 patients) using a proton pump inhibitor, clarithromycin and amoxycillin combination.21 Moreover, our study and several other European studies have reported unsatisfactory results (eradication rate < 80%),4, 6[7][8][9][10][11][12][13][14][15]–16 and similar results were also observed in a recent study performed in Japan.22 Furthermore, the eradication rate was even poorer with such treatment regimens in clinical practice (eradication rate of 67% in 469 patients).23 Therefore, more effective treatment regimens are required, so as to bring the H. pylori eradication rate closer to 100%. In one of our previous studies, we observed that the results of a treatment sequence comprising an initial 2-week dual therapy followed by a triple therapy in eradication failure patients were highly effective, while the inverse sequence gave disappointing results.20 These observations suggested that an initial treatment with amoxycillin could lead, in some way, to a higher efficacy of an eventual successive triple therapy. Therefore, in the present study, we have attempted to simplify this rather complex treatment and assessment sequence, by the use of consecutive uninterrupted short-term dual and triple therapy courses with no washout period. Using this therapy regimen, the H. pylori eradication rate obtained was very high. It is not known why an initial treatment using amoxycillin should result in a such high efficacy of the sequential treatment with a clarithromycin and tinidazole combination. Nevertheless, some hypotheses could be put forward: a reduced bacterial load after an initial amoxycillin course could facilitate H. pylori eradication during the immediately successive triple therapy course. Indeed, it has been found that a low bacterial load is associated with a high eradication rate after triple therapy regimen.24 Moreover, it has been found that amoxycillin treatment can convert H. pylori into a coccoid form, that is a viable but less virulent, and such a coccoid form may also be more susceptible to a later treatment using macrolides and imidazoles.25, 26 Consequently, further studies are warranted to verify these hypotheses. On the other hand, with the simultaneous administration of omeprazole, amoxycillin, clarithromycin and tinidazole (i.e. quadruple therapy) both more side-effects and a lower compliance rate would be expected.19, 22 Therefore, our strategy of using two consecutive treatments seems to lead both to higher efficacy and a lower rate of side-effects.

In the present study no response difference emerged between non-ulcer dyspepsia and peptic ulcer patients. This observation further strengthens the high efficacy of this treatment schedule, since it is known that H. pylori eradication following various therapy regimens can lead to a poorer response in non-ulcer dyspepsia patients than in those with peptic ulcer.11, 27, 28 This promising treatment schedule was well tolerated, safe and cheap. Indeed, further savings could be made by avoiding the urea breath test control in those patients without complicated ulcer disease when using this highly effective therapy regimen.

The successful eradication of H. pylori infection following a failed initial triple therapy is notoriously difficult to achieve, even using a 1-week quadruple therapy.17[18][19][20]–21 In such patients, we previously obtained better results using a 2-week triple therapy based on ranitidine bismuth citrate.6 This therapy regimen was also successfully used in the present study in the eradication failure patient. Although we are only dealing with a single observation, it would seem that in the event of eradication failure with the proposed 10-day regimen, we can still achieve an effective second line of defence.

In conclusion, if our results are confirmed by other studies, the use of this effective and attractive ‘five plus five’ therapy schedule could find a place in clinical practice as an initial treatment for H. pylori infection.

References

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. References
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