Bader Faiyaz Zuberi ( Departments of Medicine, Chandka Medical College Hospital, Larkana. )
Shanker Lal ( Departments of Pathology, Chandka Medical College Hospital, Larkana. )
Rafiq Muhammad Sheikh ( Departments of Medicine, Chandka Medical College Hospital, Larkana. )
To confirm the efficacy and tolerability of a new, low-dose, short-term triple therapy, 31 endoscopically diagnosed cases of peptic ulcer who were helicobacter pylon positive by brush cytology and urease test were inducted into the study. These patients were given lansoprazole 30 mg once a day, clarithromycin 250 mg twice a day and tinidazole 500 mg twice a day for one week only. Endoscopy, unease test and methylene blue test for helicobacter pylori were repeated four weeks after stopping the therapy. Ulcer healed in all the patients while helicobacter was eradicated ha 90.3% of patients (JPMA 47:228, 1997).
Helicobacter pylori (Hp) is probably the commonest infective organism in the world with an established role in chronic type B gastric and peptic ulcer1. Many drug combinations are available now a days2,3. Standard triple therapy using bismuth, metronidazole and tetracycline gives good eradication rates but the therapy is long and complicated3, moreover, the regimen is associated with significant side effects2. The introduction of eradication regimens based on acid suppression in combination with antibiotics has yielded promising results2,4,5. The combination of acid suppression with two antibiotics has provided better results3, with centers achieving eradication rates of over 80%2,6-8. Considerable more work, however, is required to identify the ideal dosage and combination that will give the best eradication rates with the simplest regimen and fewest side effects. The present study was designed to confirm the efficacy and tolerability ofa new, low dose short term triple therapy for treatment of Hp associated peptic ulcer in our settings.
Patients and Methods
Patients presenting with ulcer like symptoms undenvent upper 01 endoscopy using Fujinon F-7 endoscopc observing standard procedure and precautions9. Patients with peptic ulcer were selected for the trial. Tests for Hp were carried out in each case which included rapid urease test and brush cytology. Brush cytology was done using Teflon-sheathed re-usable brush. Sample from the brush was smeared on the slide, which was air dried and stained with 1% Methylene Blue. Slide was then observed by consultant pathologist under low power, high power and oil immersion lens for curved or ‘S’ shaped H?. Hp stains intense violet-blue with methylene blue staining Only patients with Hp positive peptic ulcer were inducted in the study. All selected patients were given cap. lansoprazole 30 rug once after breakfast, tablet clarithromycin 250 rug twice a day and tablet tinidazole 500 mg twice a day for one week only. After 4 weeks, endoscopy, rapid urease test and brush cytology were repeated. Patients were asked to report any side effects experienced.
Thirty-one patients with Hp-positive (brush cytology method) peptic ulcer were included in the trial after taking informed consent. There were 22 males and 9 females.Mean age was 29.4±6.1 years. Twenty -fourcases had duodenal ulcer and 7 had gastric ulcer. After taking the triple therapy for 7 days endoscopy was repeated at 4 wecks.It showed healing of ulcer in all patients. Hp done by brush cytology showed eradication in 28 patients (90.3%) while rapid urease test showed eradication in 29 (93.5%) patients. Only 2 (6.4%) patients reported metallic taste and nausea but were able to continuethe therapy.
Helicobacter pylori can be detected through a variety of invasive (urease testing, culture or histologic diagnosis of endoscopic biopsies) and non-invasive (urease breath tests, serologic tests) diagnostic tests. In our study we used a newly developed test for detection of Hp and found itto be sensitive and easy to perform. During follow-up endoscopy, one patient remained positive by this method in which unease test was negative thus showing a high sensitivity. In a recent report, brush cytology for detection of Hp, was shown to be significantly superior to culture, histology and urease testing9. The association of Hp in pathogenesis and treatment of peptic ulcer and chronic active type B gastritis is well established11. There is no indication to treat patients who have H pylori and non-ulcer dyspepsia or gastritis, because eradication does not reliably affect their symptoms. Current regimens for eradication include bismuth, antibiotics and anti-secretoiy agents. Complex and poorly tolerated regimens may no longer be neccssary, as simpler regimens appear to be as effective and better tolerated. In a recent study, combination of omeprazole with arnoxicillin showed 72%12 cure, while in another study combination of clarithromycin with omeprazole and nietronidazole gave 88% cure6. We in one of our previous work have shown that the combination of nizatidine with clarithromycin gave 95.2% healing7.
Many new combinations are being tried world over, stress being laid down to develop combinations which would be of short duration, low in dosage and effective in eradicating Hp and healing the ulcer. Recently a new low dose, short term triple therapy using omeprazole 20 rug b.i.d., clarithromycin 250 rug b.i.d. and tinadazole 500 rng b.i.d. for 7 days was evaluated and found to be very effective. Healing was reported in all the cases while Hp was eradicated in 93% of patients despite no further treatment13. In another study, two different short term low dose combinations were tried. These consisted of omcprazole 20 rug once in the morning and clarithromycin 250 mg and metronidazole 400 mg twice daily (0CM) for 7 days or with omeprazole 20 rug once in the morning and clarithromycin 250 rug and tetracycline 500 mg twice daily (OCD for 7 days. Hp was treated successfully in 95% patients by 0CM and in 65% patients by OCT combination14. The success of above combinations prompted us to conduct a trial using lansoprazole, clarithromycin and tinadazole in low dose for a short period of 7 days. The results obtained were very encouraging with 100% healing of ulcers and 90.3% eradication of Hp and these results matched with those from othercentres13,14. . It is concluded that this low dose, short term triple therapy is Very effective and well tolerated. The combination has few side effects and gave better compliance. The long term follow-up and relapse rate of these combinations remains to be seen by further studies.
Authors are thankful to Prof. Wazir Muhammad Sheikh for his help and guidance for the study. Help of Dr. Ghulam Muhammad Shcikh, Dr. Ghulam Ali Hulio, Dr. Lala Muzafar and Dr.Noor un Nisa Jatoi in data collection is acknowledged.
1.Parente. F.. Maconi.G.. Sangaletti, 0. et al Prevalence of Helicobacter pylori infection and related gasiroduodenal lesions in spouses of Helicobacter pylon positive patients with duodenal ulcer. Gut, 1 1996;39:629-33.
2.Axon, AT. The potential value of Iansoprasole in Helicobacter pylon eradication. J. Clin. Gastroenterol, 1995;20 (Suppl 1 ):S43-S47
3.Walsh, J.H. and Peterson, W.L. The treatment of Heticobacter pytori infection in the management of peptic ulcer. N. EngI. J. Med.. 1 995;33 3:984-91
4.Freston, J.W. Emerging strategies for managing peptic ulcer disease. Scand. J. Gastroenterol. Suppl., 1 994;20 1:49-54.
5.Kohli, Y., Kato, T., Azuma, T. et at. Lansoprazole treatment of Helicobacter pylori-positive peptic ulcers J. Ctin. Gastroenterol.. 1 995;20 (Suppl 1) S48-51 1.
6.Yousfi, MM.. el.Zimaity, H.M., al-Assi. MT. et al.Metronidazole, omeprazole and clarithromycin: An effective combination therapy for Helicobacter pylon infection. Alimen. Pharm. Ther., 1995:9:209-12.
7.Zuberi. B.F.. Sheikh, R.. Muzaffar, L. eta!. Nizatidine and Clarithromycin: An effective combination therapy in the treatment of Helicobacter py tori associ ated peptic ulcer. JCPSP. 1996;4.196.198.
8. Al-Assi, MT., Genta, R.M., Karitunen, TJ. et al. Clarithromy cin-amoxycillinc therapy for helicobacter pylori infection. Alimen. Pharm. Ther., 1994.8.453-6.
9. Kirk. R.M. Diagnostic upper gastrointestinal endoscopy. In: Dudley, H., Panics, \\\\V J and Cartes, D.C. cds. Rob and Smith’s Operative Surgery 4th Ed.. London, Butterworths, 1983. pp. 1.?.
10. Mauno, D.A., Paolo, P, Giuliano, C. et al. Brush cytology: A reliable method to detect Helicobacter pylori. J. Clin. Gastroenterol.. 1 996;22:3 17-321.
11. Hunt, RH. and Mohamed, A.H. The current role of Helicobacter pylori eradication in clinical practice. Scand. J. Gastrocriterol. Suppi . 1995;208.47-52.
12. Kodama, R., Fujiyama, K., Murakami. K. et al. Eradication therapy of Helicobacter pylon in gastroduodenal ulcer and its long-term course. Abst. Nippon-Rinsho, 1993 Dec. 51(1 2):3272-7.
13 Jaup, B.H. and Norrby, A. Low dose, short term triple therapy for cure of Helicobacter pylori infection and healing of peptic ulcers. Am. J. Gastroenterol., 1995:90:943-5.
14. Labenz. J.. Stolte, M., Ruhl, OH. et al. One-week low-dose triple therapy for the eradication of Helicobacter pylori infection. Eur. J. Gastroenterol. Hepa:ol., 1995;7 :9. 11.