Gut 1995; 37: 477-481 477 Omeprazole enhances efficacy of triple therapy in eradicating Helicobacter pyloni Gut: first published as 10.1136/gut.37.4.477 on 1 October 1995. Downloaded from

T J Borody, P Andrews, G Fracchia, S Brandl, N P Shortis, H Bae

Abstract H pylon is metronidazole sensitive or Triple therapy has been recommended resistant. as the most effective treatment for (Gut 1995; 37: 477 -481) Helicobacter pylori eradication. Despite achieving a comparatively high eradica- Keywords: Helicobacter pylon, omeprazole, eradication. tion result, however, around 10% of patients still fail to be cured. Omeprazole can enhance efficacy of single and double Eradication of Helicobacter pylori is of import- antibiotic protocols and is particularly ance in achieving a cure of duodenal and effective when combined with clarithro- gastric ulcer disease. However, the ideal thera- mycin and a nitroimidazole. This study peutic regimen for its eradication remains examined the effect of combining triple elusive. Triple therapy, using bismuth sub- therapy with omeprazole. A prospective, citrate, metronidazole, and tetracycline or randomised, unblinded, single centre amoxycillin achieves the highest eradication trial was carried out on consecutive resultsl and has therefore been recommended patients with symptoms of dyspepsia and as the preferable treatment for ulcer disease.2 H pylori infection confirmed by rapid Even with this combination of three drugs urease test, microbiological culture, and active against Hpylori, around 1 0% of patients histological assessment. Patients were fail to be cured of the infection.3 The reasons given a five times/day, 12 day course of for failure are unclear, but compliance and colloidal bismuth subcitrate chewable metronidazole resistance are thought to be of tablets (108 mg), tetracycline HCI importance.3 (250 mg), and metronidazole (200 mg) When studying H pylori eradication in with either 20 mg omeprazole twice daily patients in whom seemingly adequate treat- (triple therapy+omeprazole) or 40 mg ment with triple therapy had failed to cure the

famotidine (triple therapy+famotidine) infection,4 we found that addition of http://gut.bmj.com/ at night. Compliance and side effects omeprazole to triple therapy (quadruple were determined using a standard ques- therapy) cured overall 78% of those infected. tionnaire form. One hundred and twenty Furthermore, addition of omeprazole to five of 165 triple therapy+omeprazole monotherapy, such as amoxycillin, was known patients and 124 of 171 triple to improve H pylori eradication with success therapy+famotidine patients returned ranging from 30-80%. The few studies avail-

for rebiopsy four weeks after completion able on omeprazole combined with dual on September 24, 2021 by guest. Protected copyright. of treatment. Significantly more triple therapy also suggest eradication enhancement therapy+omeprazole patients achieved ranging from 43% to over 90%.1 2 6-10 Studies eradication 122 of 125 (97.6%) as assessed combining omeprazole with triple therapy as by negative urease test, culture, and first line of treatment have suggested consis- histological assessment, when compared tently high eradication in excess of 90/oO.ll 12 with 110 of 124 (89%) triple There has been no formal prospective work, therapy+famotidine patients (p=0.006; however, to look for any positive contribution x2). There were 30 triple therapy+ that omeprazole might give to the already high omeprazole (24%) and 26 triple ther- eradication rates achieved by triple therapy apy+famotidine (21%) patients with de currently given with H2 receptor antagonists. novo metronidazole resistant H pylon In this study we examine the effect of adding included in the study. Side effects were omeprazole to triple therapy and contrast mild and infrequent and were compar- this with the addition of famotidine to triple able in both groups, although pain in therapy, which is used routinely in our Centre for Digestive duodenal ulcer, gastric ulcer, and standard clinical protocol. Diseases, Five Dock, oesophagitis patients seemed to subside NSW, Australia earlier in those T J Borody taking omeprazole. P Andrews Compliance (>95% of drugs taken) was Methods G Fracchia achieved by 98% of patients of both S Brandl groups. A 12 day regimen of triple Patients N P Shortis H Bae therapy with omeprazole is more effec- The study was a prospective, randomised, tive in achieving H pylon eradication unblinded, single centre trial carried out on Correspondence to: to the Dr T J Borody, Centre for than is triple therapy plus famotidine. patients with dyspepsia referred Centre Digestive Diseases, 144 Use of 20 mg omeprazole twice daily for Digestive Diseases. Dyspepsia symptoms Great North Road, Five NSW Australia. rather than 40 mg famotidine with a 12 included epigastric pain or discomfort, nausea, Dock, 2046, enhances or heartburn. Accepted for publication day, low dose triple therapy vomiting, eructation, bloating 16 February 1995 eradication to over 97%/o whether the Patients were included in the study if H pylori 478 Borody, Andrews, Fracchia, Brandl, Shortis, Bae

eradication was clinically judged to be of therapy (mean (SD) 33-8 days) patients had benefit to the patient. A proportion of the another biopsy to assess H pylori eradication. patients suffering from non-ulcer dyspepsia or Urease test, histological assessment and cul- oesophagitis in whom other treatments had ture were again used to detect evidence of

failed were included in the study as there is pre- Hpylori infection. Gut: first published as 10.1136/gut.37.4.477 on 1 October 1995. Downloaded from liminary evidence that in subgroups of such categories symptomatic benefit can occur.13 14 Another significant subgroup of patients had Compliance and side effects been diagnosed previously as having radio- To obtain high eradication we endeavoured to logically or endoscopically confirmed ulcer maximise patient compliance by educating and disease but were currently endoscopically free training the patients in taking the drugs with of ulcers or scarring. All patients gave their which considerable experience had been informed consent to be included in the study, accumulated at the centre.22 Verbal explana- which was conducted in accordance with the tions and printed instructions were given to the revised Declaration of Helsinki15 and was patient. These emphasised that a totally com- approved by the ethics committee ofthe Centre pliant 'first time therapy' would guarantee a for Digestive Diseases. Patients were excluded near 100% cure while retreatment could result from the study if they had previously failed any in a considerable fall in eradication success. H pylori therapy, on the assumption that they To assess compliance, patients filled out a belonged to the 'eradication failure' category.4 standard questionnaire and were interviewed at the six week visit. This has been a successful tool in our hands as measured by eradication H pylori status success. Patients were asked to grade the side Presence of H pylori infection was assessed effects of nausea, vomiting, abdominal pain, endoscopically in every patient by rapid urease oral discomfort, diarrhoea, constipation, and test, histological examinations, and microbio- rash from nil to severe. Scores were assigned logical culture of gastric biopsy specimens according to severity in the following way: nil, obtained before the treatment and four weeks score 0; no side effects experienced: mild, after completion of triple therapy. All examina- score 1; effects seen but could be disregarded: tions were performed by the same endoscopist moderate score 2; effects bad enough to call (TJB) with the specimens taken from the doctor but could continue treatment and gastric antrum and body. The methods used tolerate discomfort: severe, score 3; effects have been described previously16 17 and will be interfered with activities at work; side effects summarised here. One antral specimen was had to be treated or triple therapy had to be placed in a microtitre tray, which contained discontinued. In practice, a score of 1 was

buffered urea and an indicator for rapid assigned to patients who did not recall side http://gut.bmj.com/ detection of urease activity as previously effects when asked 'did you have any side described.18 Two antral specimens were taken effects?' but who recalled experience of side for microbiological culture, which in our hands effects when confronted with a list of is the most sensitive method of detecting the individual side effects. A score of 2 or more presence of H pylori 16 17 One antral and one was given when patients could recall side gastric body specimen was placed in 10% effects without prompting. For this reason, buffered formalin for histological examination only scores of2 or 3 were included as 'clinically on September 24, 2021 by guest. Protected copyright. carried out using a modified Giemsa stain. The significant side effects'. results were considered Hpylori positive if any one of the three tests used (rapid urease, microbiology or histology) showed evidence of Statistical analysis H pylori infection. Metronidazole resistance H pylori eradication for the triple therapy was determined on chocolate agar by compara- regimens with famotidine and omeprazole was tive disc diffusion (50 ,ug concentration) using compared using the x2 test. The differences NCTC 1 1639 reference H pylori strain. between mean values of side effects' severity in Resistance was deemed present with a zone of the two groups and mean number of doses inhibition of less than 5 mm. missed by non-compliant patients were deter- mined by Student's t test. All values with p<005 were considered to be statistically Treatment significant. Patients were given a triple therapy regimen consisting of chewable colloidal bismuth sub- citrate (De Nol; 108 mg), tetracycline HCI Results (250 mg), and metronidazole (200 mg) five A total of 165 and 171 patients were randomly times per day20 (7 am, 11 am, 3 pm, 7 pm, assigned to the triple therapy plus omeprazole 11 pm) for 12 days with either omeprazole and triple therapy plus famotidine groups (20 mg) at 7 am and 7 pm or famotidine respectively. One hundred and twenty five (40 mg) at 11 pm only. The omeprazole dose patients returned following the triple ther- was chosen to be equivalent to that used apy+omeprazole regimen (75.8%) and 124 in the omeprazole-amoxycillin trials.21 The patients who received triple therapy+famoti- famotidine 40 mg night time dose had dine regimen (72.5%), four weeks after com- replaced ranitidine as our standard H2 receptor pletion of treatment. antagonist combined with triple therapy.20 At Despite a complete phone follow up and least four weeks after the completion of triple remuneration offer a significant number of Optimal H pylori therapy 479

TABLE I Demographic data ofpatients included in the results were found, however, and there was a study 70% chance of finding them if they were Tnple therapy+ Tiple therapy+ present. oineprazole famotidine

Number 125 124 Gut: first published as 10.1136/gut.37.4.477 on 1 October 1995. Downloaded from Mean age (SD) 51-4 (12-8) 52.5 (15.5) Side effects Male/female 60/65 67/57 Eradication of H pylori (%) 122/125 (97.6) 110/124 (89) Severity of side effects experienced by the Diagnosis patients in the two groups was compared. Duodenal ulcer 38 34 Gastric ulcer 5 3 Table II lists the frequencies of side effects Non-ulcer dyspepsia 50 37 with the most frequent being nausea, occurring Oesophagitis 22 23 Other (past history of ulcer) 11 21 in 7.2% (triple therapy+omeprazole) and 12.6% (triple therapy+famotidine) patients Some patients had multiple diagnoses. followed by oral discomfort in 5.40/o and 6.8%, presumed to be caused by transient oral can- patients could not be induced to undergo the didiasis. Patient compliance did not seem to be second endoscopy, often for a variety of affected by these usually minor side effects. economic reasons including preservation of Furthermore, there was no statistically signifi- employment status. In addition, as in our pre- cant difference in scores for nausea, vomiting, vious studies, most (64% of those contacted) abdominal pain, oral discomfort, diarrhoea or claimed they were feeling well and did not constipation between the two groups. wish to proceed with the re-endoscopy. Although not measured by the questionnaire, Symptomatic patients were more interested to there was a distinct clinical impression that see whether they still carried the infection20 23 dyspeptic symptoms, especially abdominal and returned more frequently for rebiopsy. pain, abated more rapidly in patients using The bias in the study was therefore towards the omeprazole. H pylori positive patients returning with a pre- sumed equivalent 'loss to follow up' occurring in each of the study arms. Compliance Of the patients who returned for re- Based on self reporting, 970/o of patients in the endoscopy 111 in the triple therapy+ triple therapy+omeprazole group and 96% of omeprazole group and 103 in the triple ther- those treated with triple therapy+famotidine apy+famotidine group filled out side effect were '100% compliant' with the treatment. questionnaire forms. Demographic data and There was no statistical difference between the predominant endoscopic diagnosis for all two results (p=0.628). patients included in the analysis of the study was listed. There were no significant demo- graphic or diagnostic differences between the Metronidazole resistance http://gut.bmj.com/ groups of patients using triple therapy with De novo metronidazole resistance was found either omeprazole or famotidine (Table I). to be present in 24% of patients in the triple therapy+ omeprazole and 21/% triple therapy+ famotidine groups. Using the culture method- H pylori eradication ology described and particularly that of placing H pylori was judged to be eradicated in 122 of gastric biopsy specimens directly onto the 125 (97.6%) patients using the triple ther- culture plate from the biopsy forceps, H pylori on September 24, 2021 by guest. Protected copyright. apy+omeprazole regimen. Conversely, 1 10 of growth was obtained in all patients studied. 124 (89%) patients were cured ofHpylori using Although it is recognised that in many centres triple therapy+famotidine regimen. All three H pylori culture is achieved in no more than tests used, urease, histological assessment, and 80% of instances as it was in the early days in microbiology, had to be negative to consider our laboratory, our current success rate in over H pylori as being eradicated. There was a 8000 patients approaches 98%.l7 Of the three significant statistical difference found between patients who failed to eradicate Hpylori in the these eradication results (p=0-006; X2). The triple therapy+omeprazole group one of three initial sample (165 triple therapy+omeprazole was metronidazole resistant, another had and 171 triple therapy+famotidine patients) recently (within the past four weeks) taken a would have provided more than 80% power course of amoxycillin, while the last was (the usual value used) to the study but the drop incompletely compliant to the treatment. out rate was higher than expected so that in the end the power was 70%. Statistically significant Discussion TABLE II Comparison ofside effects between triple therapy plus omeprazole (TT+ 0) and This study describes the use of triple therapy triple therapy plus famotidine (TT+F), either as scores or absolute values combined with omeprazole for 12 days. When used in compliant Australian patients this pro- Clinically significant Mean (SEM) score side effects (%o) tocol approaches 100% (97.6%) eradication. Other clinicians have reported such a combi- Symptoms TT+0 TT+F p Value TT+0 TT+F p Value nation to be highly efficacious. Hosking et al, 1 1 Nausea 0-36 (0.07) 0-42 (0.06) 0.5 7-2 12-6 0-18 in Hong Kong, using only 20 mg omeprazole Vomiting 0.07 (0.04) 0.07 (0.03) 1 1-8 1-9 0-94 Abdominal pain 0.25 (0.05) 0-21 (0.04) 0.54 2-7 1.9 0.71 in the morning together with colloidal Oral discomfort 0.24 (0.06) 0-25 (0.05) 0.9 5 4 6-8 0-67 bismuth subcitrate, tetracycline 500 mg, and Diarrhoea 0.13 (0.04) 0.13 (0.04) 0.87 1.8 1.9 0 94 Constipation 0.06 (0.03) 0.05 (0.02) 0.78 0.9 0.9 0-96 metronidazole 400 mg four times daily (n=78) achieved eradication in 95%/n of patients using 480 Borody, Andrews, Fracchia, Brandl, Shortis, Bae

only a seven day course. This group subse- omeprazole alone. 1" In this study the combina- quently published another, similar study, tion of five times/day triple therapy with which resulted in 98% eradication.24 In omeprazole resulted in infrequent, mild, and Australia, with a smaller patient group (n= 25), certainly clinically insignificant level of adverse reactions. Though not Daskalopoulos et a112 used a 14 day course measured directly, it Gut: first published as 10.1136/gut.37.4.477 on 1 October 1995. Downloaded from of omeprazole 20 mg/day with colloidal bis- was our impression that the addition of muth subcitrate, tetracycline 250 mg, and omeprazole shortened duration of dyspeptic metronidazole 200 mg four times daily, achiev- symptoms in those patients with ulcers and ing 96% (24 of 25) eradication. Such results reflux symptoms. corroborate our 97.6% result carried out in a In vitro metronidazole resistance of H pyloni large patient cohort, using lower treatment is currently being invoked as perhaps the major doses. Our patients took 750 mg less obstacle to more successful eradication when tetracycline and 600 mg less metronidazole per using triple therapy.5 27 29 30 Metronidazole day though omeprazole was 20 mg twice daily resistance therapeutic studies, however, have v 20 mg/d. A further finding of this study is the yet to differentiate between patients with de higher H pylori eradication by triple therapy novo and post therapy metronidazole resis- achieved by substituting 40 mg omeprazole for tance.28 31 Indeed, when compliant patient 40 mg famotidine. This finding suggests that populations with and without de novo omeprazole indeed contributes to the improve- metronidazole resistant bacteria are compared, ment in eradication. Hpylorz eradication with triple therapy is virtu- Although this protocol may seem cumber- ally equivalent.19 On the other hand, there is some it works well in clinical practice perhaps general agreement that after failed antibiotic because it is brief. Furthermore it is feasible to treatment H pylori becomes less responsive to combine the three components of triple ther- re-treatment and even complex antibiotic com- apy into a fixed dose combination therapy as a binations achieve but modest eradication single tablet. This would simplify dosing and results6 32 33 suggesting that prior, recent enhance compliance. In view of the 95% exposure to antibiotic treatment or to eradication obtained by Hosking et al11 using a omeprazole,34 may be the major cause of sub- seven day protocol it seems probable that a sequent eradication failure. In fact in vitro single tablet could be given for only seven days 'metronidazole resistance' can develop without without significant loss of efficacy and perhaps metronidazole use35 and rather than achieving with further reduction in component doses of high eradication, metronidazole free triple triple therapy. Indeed, a one day triple therapy therapy (bismuth subcitrate, amoxycillin, (CBS 240 mg X4; amoxycillin 2 g X4; tetracycline) has achieved a mere 20% metronidazole 500 mg X 4) with 40 mg success.36 It is therefore of clinical importance that addition of twice daily omeprazole to

omeprazole, has achieved an eradication of http://gut.bmj.com/ 72%.25 Therefore, there seems to be scope for triple therapy can virtually remove the per- the reduction not only of triple therapy ceived problem of metronidazole resistance. component doses but also for the reduction in With a de novo, in vitro resistance status of treatment duration. 24% in our triple therapy+omeprazole group The use of a simplified protocol using and H pylori eradication rates of 97.6% omeprazole and amoxycillin has recently metronidazole resistance seems to be of no clinical relevance. Such also were the findings

attracted much interest. Variable and often on September 24, 2021 by guest. Protected copyright. conflicting eradication results have emerged, of Hosking et al24 who achieved 98% eradica- however, ranging from 28-82%. This led tion in his group of patients despite 48% Collins et al 5 to conclude that 'based on metronidazole resistance. present evidence, omeprazole and amoxycillin In conclusion, a 12 day course of lower dose cannot yet be considered the optimal regimen five times/day triple therapy combined with 20 for eradicating H pylori'. The best of the latest mg twice daily omeprazole seems to be an published protocols using the dual therapy efficient protocol achieving, in unselected achieves an 80-82% eradication in a popu- patients, an eradication of H pylori of lation selected out for penicillin sensitive 97.6% whether it be resistant de novo to patients.23 26 This selection further reduces the metronidazole or not. The high eradication eradication to <80% when considering 'all may permit further reduction of triple therapy comers'. The major restriction of amoxycillin component dose and a shorter duration of containing eradication therapies is the exist- treatment without loss of efficacy. ence of penicillin sensitivity in a significant 1 Chiba N, Rao BV, Rademaker JW, Hunt RH. Meta-analysis proportion of the population, which will of the efficacy of antibiotic therapy in eradicating prevent eradication ever approaching 100% Helicobacter pylori. AmJ7 Gastroenterol 1992; 87: 1716-27. 2 Axon ATR. Helicobacter pylori therapy: effect on peptic described here. Tetracycline containing triple ulcer disease. Jf Gastroenterol Hepatol 1991; 6: 131-7. therapy does not suffer from this disadvantage 3 Ruaws EAJ. Reasons for failure of Helicobacter pylori treat- ment. European Journal of Gastroenterology and Hepatology and is therefore amenable to further optimisa- 1993; 5 (suppl 2): S92-5. tion. 4 Borody TJ, Brandl S, Andrews P, Jankiewicz E, Ostapowicz Side effects of triple therapy have N. H pyloni eradication failure (EF) - further treatment been used possibilities. Gastroenrerologry 1992; 102: A43. as an argument to develop alternative 5 Collins R, Beattie S, Xis HX, O'Morain C. Short report: high-dose omeprazole and amoxycillin in the treatment of protocols.26 Side effects of triple therapy are Helicobacter pylori-associated duodenal ulcer. Aliment generally minor, however,2S28 reduced by the Pharmacol Ther 1993; 7: 313-5. lower dose triple therapy recently 6 Al-Assi MT, Genta RM, Graham DY. Failure of omepra- intro- zole to enhance antimicrobial therapy for H pyloni: duced,20 and clinically have been found to be omeprazole with tetracycline or tetracycline and bismuth. no different by some to side effects of AinJ Gastroenterol 1993; 88: 1502. Optimal H pylori therapy 481

7 McCarthy CJ, Collins R, Beattie S, Hamilton H, O'Morain 22 Borody TJ. Possibilities for Helicobacter pylori suppres- C. Short report: treatment of Helicobacter pylori-associ- sion/eradication. European Journal of Gastroenterology and ated duodenal ulcer with omeprazole plus antibiotics. Hepatology 1992; 4 (suppl 2): S37-40. Aliment Pharmacol Ther 1993; 7: 463-6. 23 Borody TJ, Andrews P, Mancuso N, Macauley D, 8 Bell GD, Powell KU, Burridge SM, Rameh B, Bolton G, Jankiewicz E, Ferch N, et al. Helicobacter pylori reinfec- Purser K, et al. Helicobacter pylori eradication: a combi- tion rate, in patients with cured duodenal ulcer. Am J metronidazole nation of omeprazole, amoxycillin and Gastroenterol 1994; 89: 529-32. Gut: first published as 10.1136/gut.37.4.477 on 1 October 1995. Downloaded from compared with standard triple therapy. Gut 1993; 34 24 Hosking SW, Ling TKW, Chung SCS, Yung MY, Cheng (suppl 1): S37. AFB, Sung JJS, et al. Duodenal ulcer healing by eradica- 9 Moayyedi P, Axon ATR. Efficacy of a new one week triple tion of Helicobacter pylori without anti-acid treatment: therapy regime in eradicating Helicobacter pylori. Gut randomised controlled trial. Lancet 1994; 343: 508-10. 1994; 35 (suppl 2): S62. 25 Tucci A, Corinaldesi R, Stanghellini V, Paparo GF, 10 Bazzoli F, Zagary RM, Fossi S, Pozzato P, Roda A, Roda E. Gasperoni S, Biasco G, et al. One-day therapy for treat- Efficacy and tolerability of short term low-dose triple ment of Helicobacter pylori infection. Dig Dis Sci 1993; therapy for eradication of Helicobacter pylori. 38: 1670-3. Gastroenterology 1993; 104: A40. 26 Labenz J, Gyenes E, Ruhl GH, Borsch G. Amoxycillin plus 11 Hosking SW, Ling TKW, Yung MY, Cheng A, Chung omeprazole versus triple therapy for eradication of SCS, Leung JWC, et al. Randomised controlled trial of Helicobacter pylori in duodenal ulcer disease: a prospec- short term treatment to eradicate Helicobacter pylori in tive, randomised, and controlled study. Gut 1993; 34: patients with duodenal ulcer. BMJ3 1992; 305: 502-4. 1167-70. 12 Daskalopoulos G, Carrick J, Lian R, Lee A. Optimising 27 Thijs JC, Van Zwet AA, Oey HB. Efficacy and side effects therapy for .H pylori gastritis. Ir J Med Sci 1992; 166 of a triple drug regimen for the eradication ofHelicobacter (suppl 10): 16. pylori. ScandJ7 Gastroenterol 1993; 28: 934-8. 13 Borody T, Andrews P, Brandl S, Macauley D, Hyland L. 28 Burette A, Glupczynski Y, De Prex C. Evaluation ofvarious Does H pylori (HP) play a role in esophageal reflux? multi-drug eradication regimens for Helicobacter pylori. Gastroenterology 1993; 104: A44. EurJ Gastroenterol Hepatol 1992; 4: 817-23. 14 O'Morain C. Helicobacter pylori and non-ulcer dyspepsia. 29 Tytgat GNJ, Noach LA, Rauws EAJ. Helicobacter pylori. Gastroenterology 1992; 103: 340-7. EurJ Gastroenterol Hepatol 1992; 4 (suppl 1): S7-15. 15 World Medical Assembly. The Declaration of Helsinki. 30 Bell GD, Powell K, Burridge SM, Harrison G, Weil J, Gant World Med J 1982; 29: 86-8. PW, et al. Does a previous course oftripotassium dicitrato 16 Borody TJ, George LL, Brandl S, Andrews P, Ostapowicz bismuthate affect the subsequent changes of successful N, Hyland L, et al. Helicobacter pylori-negative duodenal Helicobacter pylori eradication? Aliment Pharmacol Ther ulcer. Am J Gastroenterol 199 1; 89: 1154-7. 1992; 6: 327-33. 17 Borody TJ, Andrews PJ, Brandl S, Hyland L, Morgan A, 31 Xia H, Daw MA, Sant S, Beattie S, Keane CT, O'Morain Ostapowicz N, et al. Endoscopic diagnosis ofHelicobacter CA. Clinical efficacy of triple therapy in Helicobacter pylori (H pylori) - approaching the 'Gold Standard'. pylori-associated duodenal ulcer. Eur J Gastroenterol Abstracts ofthe World Congresses ofGastroenterology, Sydney, Hepatol 1993; 5: 141-4. 1990. Abingdon: The Medicine Group (UK) Ltd, 1990: 32 Marshall BJ, Guerrant RL, Hoffman SR, Barrett RW, PD91. McCallum RW. Eradication of metronidazole resistant H 18 Hazell SL, Borody TJ, Gal A, Lee A. Campylobacter pylori pylori [Abstract]. Am Gastroenterol 199 1; 86: 1315. gastritis. I: Detection of urease as a marker of bacterial 33 Seppala K, Sipponen P, Farkkila M, Kosunen TU. colonisation and gastritis. Am J Gastroenterol 1987; 82: Quadruple therapy eradicates nitroimidazole resistant H 292-6. pylori. Acta Gastroenterolog Belg 1993; 56: 66. 19 Borody T, Andrews P, Brandl S, Devine M. Relevance of 34 Labenz J, Gyenes E, Ruhl H, Borsch G. Pretreatment with in-vitro metronidazole resistance to H pylori (HP) eradi- omeprazole endangers the efficiency of cation and eradication failure. Gastroenterology 1993; 104: amoxicillin/omeprazole treatment to eradicate HP. Ir J A44. Med Sci 1992; 161 (suppl 10): 12. 20 Borody TJ, Brandl S, Andrews P, Ferch N, Jankiewicz E, 35 Daskalopoulos G, Carrick J, [ian RX, Lee A. The silent Hyland L. Use of high efficacy, lower dose triple therapy minority - eradication of Helicobacter pylori infection to reduce side effects of eradicating Helicobacter pylori. where standard triple therapy has failed. H pylori. Basic Am Y Gastroenterol 1994; 89: 33-8. mechanisms to clinical cure. Interfalk Conference Proceedings: 21 Labenz J, Gyenes E, Ruhl GH, Borsch G. Omeprazole plus Ritz-Carlton Hotel, Amelia IS FL; Nov 3-6, 1993: 36. amoxycillin: efficacy of various treatment regimens to 36 Graham DY, Lew GM, Klein PD, Genta RM, Evans DG. eradicate Helicobacter pylori. Am J Gastroenterol 1993; A new triple therapy without metronidazole for Helico- http://gut.bmj.com/ 88: 491-5. bacter pylori infection. Gastroenterology 1992; 102: A76. on September 24, 2021 by guest. Protected copyright.