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May 2000, Volume 50, Issue 5

Short Reports

Two Weeks Triple Therapy with Lansoprazole, Amoxycillin and Roxythromycin is better than dual Therapy with Lansoprazole and Amoxycillin for H. pylon Infection: A Randomised, Clinical Trial

Hurna Qureshi  ( PMRC Research Centre Jinnah Postgraduate Medical Centre, Karachi. )
Itrat Mehdi  ( PMRC Research Centre Jinnah Postgraduate Medical Centre, Karachi. )
Ejaz Alam  ( PMRC Research Centre Jinnah Postgraduate Medical Centre, Karachi. )

Abstract

Aims: To compare the efficacy of 2 weeks of dual therapy of Lansoprazole and Amoxycilline with triple therapy of Lansoprazole, Amoxycilline and Roxythromycin for H. pylori eradication.
Subjects: Twentyfive suffering from dyspepsia and found H. pylon positive (CLO) during upper Cl endoscopy.
Methods: Patients were divided into 2 groups,one group received Lansoprazole (30mg) once a day, and amoxycilline (500mg) three times a day (group I),while the second group received Lansoparazole and amoxycillin in similar dosage with the addition of Roxythromycin (150mg) twice a day (group II). H. pylori status was confirmed on endoscopy using CLO test at entry to the protocol and then at 4 weeks.
Results: H. pylori eradication was 57% in group I and 86% in group II with healing of lesions in all cases. Conclusion: Better response with triple therapy (group II) indicates enhanced eradication of the pathogens with triple therapy while using roxythromycin (JPMA 50:157, 2000).

Introduction

Various drug combinations have been used for H. pylori eradication with varied results1-3. Generally triple therapy using a proton pump inhibitor with two antibiotics gives satifactory results4-5. In one study omeprazole combined with amoxycillin alone or with amoxycillin and rnetrbnidazole were found equally effective in H. pylori eradication5 while omeprazole plus clarithromycin and tetracyclin gave poor results6 but similar combination with tinidazole gave better results6. There is a general fear that metronidazole tolerance is decreasing and its resistance increasing world over4,7-9. Therefore most new combinations are replacing metronidazole with macrolides like clarithromycin10 or roxithromycin5,8.
Most antibiotics are able to kill H.Plyori when it is in a dividing state because during this state some specific proteins are produced to which antiobiotics are sensitive (Amoxycillin and Clarithromycin)11. Proton pump inhibitors increase the pH of gastric mucosa and make the non dividing non protein producing H. pylori into dividing H. pylon and thus increase and enhance the H. pylori’s sensitivity to antibiotics like Amoxycillin and Clarithromycin11. Metron idazole attacks on the DNA therefore its effect is not related to the pathogen’s dividing status’s.
In the present study two antibiotics (Roxithrornycin and or Amoxycillin) were used with a proton pump inhibitor to see if the effect of two antibiotics is enhanced when compared with a single antibiotic.

Patients, Methods and Results

Adult patients undergoing upper G.l. endoscopy for symptoms of acid peptic disease were included in the study. Patients already on antibiotics or anti ulcer treatment, upper G.l. bleeders and those with malignancy or chronic liver or renal disease were excluded from the study.
Upper G.l. efldoCopy was done in a fasting state using Olympus or Fujinon scopes. After complete examination of the esophagus. stomach and duodenum, an antral biopsy was taken and embeded immediately in the CLO gel using a disposable needle. The color change of the gel from yellow to magenta within I 5 minutes was taken as a positive test while late positives and those that remained yellow were taken as negative. Irrespective of the presence or absence of lesion on endoscopy. all cases that were CLO positive within 15 minutes of embedding were given H. pylon clearance therapy after informed consent. Two drug combinations were used ie Lansoprazole 30 mg (Lanzol) once a day before breakfast with Amoxycillin 500mg three times a day ( Group I) or Lansoprazole with Amoxycillin in the same dose plus Roxithroniycin (Rulid) 150mg twice a day (group II), using systematic randomization. Drugs were given for 14 days and endoscopy plus CLO test were repeated at 28th day. Those cases in whom CLO remained negative at 15 minutes were taken as respondants while those whose CLO showed a color change within 15 minutes were labelled as non respondants. Relief of symptoms was also evaluated at the end of the study.
A total of 4 cases were enrolled for the study of whom 8 were lost to followup and I has yet to complete the therapy leaving 36 cases for evaluation.
There were 26 males and 10 females whose ages ranged from 28 to 35 years (mean 28 years). On endoscopy 26 cases had no lesion. 6 had gastritis or duodenitis and 4 had duodenal ulcer. CLO was positive in all cases. Using systematic randomization, 23 cases in group 1 and 22 in group II received the drug but at the end of the study after excluding the lost to followup cases, 22 had received Lansoparazole with Amoxycillin (group I) and 14 Lansoparazo le. Amoxvc ill in with Rox ithromyc in (group 11).
After 2 weeks of therapy 13 cases (57%) in group I and 12 cases (86°/a) in group II cleared infection with H. pylori by showing negative CLO test, while 9 cases (43%) in group I and 2 cases (14%) in group II were still CLO positive. H. pylori clearance rate was better in group 11 (not significant) suggesting that addition of Rox\\\\thromycin either potentiated the effect of amoxycillin or acted synergistically and produced better H. pylon clearance.

Comments

H. pylori plays a major role in the occurrence of gastroduodenitis and duodenal ulcer. Its eradication not only results in healing of the lesion and also prolongs the remission of the disease especially in duodenal ulcer6,12-14. Eradication of this pathogen was initially tried with Bismuth preparation plus metronidazole and another antibiotic like amoxycillin or tetracycline’. Resistance to metronidazole7,9,15 and other commonly used antibiotics’ and lack of compliance to longer duration of therapy (4 weeks) and too many drugs (9 tablets daily) lead to revising the treatment strategy. Newer antibiotics like Clarithromycin and macrolides like Roxithrornycin with proton pump inhibitors were used with an attempt to not only reduce the chances of resitance but also produce better compliance, rapid healing and early eradication by disturbing the environment of H. pylon. Goh6 reported 79% and 86% H. pylori eradication when using 40mg of Omperazole once a day with Amoxycillin alone or in combination with Metronidazole and they suggested that dual therapy is not only effective but also well tolerated. Similar results were reported with a one week’s therapy of omeprazole plus clarithrornycin and tinidazole6 but poor response was achieved when low dose Tetracycline was used instead of Tinidazole6. Higher dose i.e., 500mg Tetracyc line four times a day gives better results. H istory of smoking and previous use of H2 blockers have been failure. Moreover short term triple therapies do not seem to produce reproducible results worldwide and it reported to be associated with short term triple therapy is generally accepted that good eradication results are difficult to achieve with short term dual or triple therapies6. therefore two weeks of dual or triple therapies are recommended for H. pylon eradication.
Using a similar hut twice a day regimen of lansoparazole 30mg. clarithrom\\\\c in 500mg and amoxycillin Igram for 2 weeks, Schawtz et al5 repouted a 94% eradication of H. p\\\\lori. but this figure dropped to 57% and 53% respectively for patients receiving dual therapy of lansoprazole and clarithromycin or lansoprazole and amoxycillin. It is also reported that primary resistance to clarithnomvcin is around in Europe16,17, while secondary resistance develops less frequently when proton pump inhibitors are used in clarithromycin and another antibiotic. as compared with proton pump inhibitor and clarithromycin18.
In the present study two weeks triple therapy comprising of Lansoprazole. amoxvcillin and Roxithromvcin showed better response (86%) than that achieved with dual therapy (57%) in H. pylon eradication. Addition of Roxythromycin had a synergistic antibiotic effect on the bacterium theneb improving the response. In the present study though the cost of therapy was exceptionally high but better eradication of H. pylori was achieved when compared with dual therapy.

Acknowledgement

The supply of drugs and support of trial Pharmatec Pakistan (Pvt.) Ltd. is greatly appreciated.

References

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