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. 1996 Jul;39(1):54–59. doi: 10.1136/gut.39.1.54

Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

J Thorens 1, F Froehlich 1, W Schwizer 1, E Saraga 1, J Bille 1, K Gyr 1, P Duroux 1, M Nicolet 1, B Pignatelli 1, A L Blum 1, J J Gonvers 1, M Fried 1
PMCID: PMC1383231  PMID: 8881809

Abstract

BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four week treatment regimen with omeprazole 20 mg or cimetidine 800 mg daily. Gastric and duodenal juice were obtained during upper gastrointestinal endoscopy and plated for anaerobic and aerobic organisms. RESULTS: Bacterial overgrowth (> or = 10(5) cfu/ml) was present in 53% of the patients receiving omeprazole and in 17% receiving cimetidine (p < 0.05). The mean (SEM) number of gastric and duodenal bacterial counts was 6.0 (0.2) and 5.0 (0.2) respectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the cimetidine group (p < 0.001 and < 0.01; respectively). Faecal type bacteria were found in 30% of the patients with bacterial overgrowth. Basal gastric pH was higher in patients treated with omeprazole compared with cimetidine (4.2 (0.5) versus 2.0 (0.2); p < 0.001) and in patients with bacterial overgrowth compared with those without bacterial overgrowth (5.1 (0.6) versus 2.0 (0.1); p < 0.0001). The nitrate, nitrite, and nitrosamine values in gastric juice did not increase after treatment with either cimetidine or omeprazole. Serum concentrations of vitamin B12, beta carotene, and albumin were similar before and after treatment with both drugs. CONCLUSIONS: These results show that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine. This can be explained by more pronounced inhibition of gastric acid secretion. No patient developed signs of malabsorption or an increase of N-nitroso compounds. The clinical significance of these findings needs to be assessed in studies with long-term treatment with omeprazole, in particular in patients belonging to high risk groups such as HIV infected and intensive care units patients.

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Selected References

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  1. Armbrecht U., Seeberg S., Stockbrügger R. W. Hydrogen (H2) breath excretion in peptic disease before and during treatment with ranitidine. Scand J Gastroenterol. 1987 Dec;22(10):1211–1216. doi: 10.3109/00365528708996466. [DOI] [PubMed] [Google Scholar]
  2. Bardhan P. K., Gyr K., Beglinger C., Vögtlin J., Frey R., Vischer W. Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy. Scand J Gastroenterol. 1992;27(3):253–256. doi: 10.3109/00365529208999959. [DOI] [PubMed] [Google Scholar]
  3. Batman P. A., Miller A. R., Sedgwick P. M., Griffin G. E. Autonomic denervation in jejunal mucosa of homosexual men infected with HIV. AIDS. 1991 Oct;5(10):1247–1252. doi: 10.1097/00002030-199110000-00015. [DOI] [PubMed] [Google Scholar]
  4. Belitsos P. C., Greenson J. K., Yardley J. H., Sisler J. R., Bartlett J. G. Association of gastric hypoacidity with opportunistic enteric infections in patients with AIDS. J Infect Dis. 1992 Aug;166(2):277–284. doi: 10.1093/infdis/166.2.277. [DOI] [PubMed] [Google Scholar]
  5. Bourne J. T., Mountford R. A., Barry R. E. Twice-daily cimetidine does not increase gastric bacterial flora. Postgrad Med J. 1984 Jul;60(705):464–466. doi: 10.1136/pgmj.60.705.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Budhraja M., Levendoglu H., Kocka F., Mangkornkanok M., Sherer R. Duodenal mucosal T cell subpopulation and bacterial cultures in acquired immune deficiency syndrome. Am J Gastroenterol. 1987 May;82(5):427–431. [PubMed] [Google Scholar]
  7. Chave J. P., Thorens J., Fröhlich F., Gonvers J. J., Glauser M. P., Bille J., Gyr K., Fried M. Gastric and duodenal bacterial colonization in HIV-infected patients without gastrointestinal symptoms. Am J Gastroenterol. 1994 Dec;89(12):2168–2171. [PubMed] [Google Scholar]
  8. Chen V. W., Abu-Elyazeed R. R., Zavala D. E., Haenszel W., Ktsanes V. K., Rice J., Cuello C., Montes G., Correa P. Risk factors of gastric precancerous lesions in a high-risk Colombian population. II. Nitrate and nitrite. Nutr Cancer. 1990;13(1-2):67–72. doi: 10.1080/01635589009514046. [DOI] [PubMed] [Google Scholar]
  9. Corazza G. R., Menozzi M. G., Strocchi A., Rasciti L., Vaira D., Lecchini R., Avanzini P., Chezzi C., Gasbarrini G. The diagnosis of small bowel bacterial overgrowth. Reliability of jejunal culture and inadequacy of breath hydrogen testing. Gastroenterology. 1990 Feb;98(2):302–309. doi: 10.1016/0016-5085(90)90818-l. [DOI] [PubMed] [Google Scholar]
  10. Correa P. A human model of gastric carcinogenesis. Cancer Res. 1988 Jul 1;48(13):3554–3560. [PubMed] [Google Scholar]
  11. Cristiano P., Paradisi F. Can cimetidine facilitate infections by oral route. Lancet. 1982 Jul 3;2(8288):45–45. doi: 10.1016/s0140-6736(82)91179-5. [DOI] [PubMed] [Google Scholar]
  12. Drasar B. S., Shiner M., McLeod G. M. Studies on the intestinal flora. I. The bacterial flora of the gastrointestinal tract in healthy and achlorhydric persons. Gastroenterology. 1969 Jan;56(1):71–79. [PubMed] [Google Scholar]
  13. Driks M. R., Craven D. E., Celli B. R., Manning M., Burke R. A., Garvin G. M., Kunches L. M., Farber H. W., Wedel S. A., McCabe W. R. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. The role of gastric colonization. N Engl J Med. 1987 Nov 26;317(22):1376–1382. doi: 10.1056/NEJM198711263172204. [DOI] [PubMed] [Google Scholar]
  14. Ellakany S., Whiteside T. L., Schade R. R., van Thiel D. H. Analysis of intestinal lymphocyte subpopulations in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Am J Clin Pathol. 1987 Mar;87(3):356–364. doi: 10.1093/ajcp/87.3.356. [DOI] [PubMed] [Google Scholar]
  15. Forsythe S. J., Dolby J. M., Webster A. D., Cole J. A. Nitrate- and nitrite-reducing bacteria in the achlorhydric stomach. J Med Microbiol. 1988 Apr;25(4):253–259. doi: 10.1099/00222615-25-4-253. [DOI] [PubMed] [Google Scholar]
  16. Fried M., Siegrist H., Frei R., Froehlich F., Duroux P., Thorens J., Blum A., Bille J., Gonvers J. J., Gyr K. Duodenal bacterial overgrowth during treatment in outpatients with omeprazole. Gut. 1994 Jan;35(1):23–26. doi: 10.1136/gut.35.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gray J. D., Shiner M. Influence of gastric pH on gastric and jejunal flora. Gut. 1967 Dec;8(6):574–581. doi: 10.1136/gut.8.6.574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
  19. Hall C. N., Darkin D., Brimblecombe R., Cook A. J., Kirkham J. S., Northfield T. C. Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in precancerous conditions. Gut. 1986 May;27(5):491–498. doi: 10.1136/gut.27.5.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hamilton I., Worsley B. W., O'Connor H. J., Axon A. T. Effects of tripotassium dicitrato bismuthate (TDB) tablets or cimetidine in the treatment of duodenal ulcer. Gut. 1983 Dec;24(12):1148–1151. doi: 10.1136/gut.24.12.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hillman K. M., Riordan T., O'Farrell S. M., Tabaqchali S. Colonization of the gastric contents in critically ill patients. Crit Care Med. 1982 Jul;10(7):444–447. doi: 10.1097/00003246-198207000-00005. [DOI] [PubMed] [Google Scholar]
  22. Holt P. R., Rosenberg I. H., Russell R. M. Causes and consequences of hypochlorhydria in the elderly. Dig Dis Sci. 1989 Jun;34(6):933–937. doi: 10.1007/BF01540281. [DOI] [PubMed] [Google Scholar]
  23. Howden C. W., Hunt R. H. Relationship between gastric secretion and infection. Gut. 1987 Jan;28(1):96–107. doi: 10.1136/gut.28.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Howden C. W., Hunt R. H. Relationship between gastric secretion and infection. Gut. 1987 Jan;28(1):96–107. doi: 10.1136/gut.28.1.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Husebye E., Skar V., Høverstad T., Melby K. Fasting hypochlorhydria with gram positive gastric flora is highly prevalent in healthy old people. Gut. 1992 Oct;33(10):1331–1337. doi: 10.1136/gut.33.10.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lake-Bakaar G., Tom W., Lake-Bakaar D., Gupta N., Beidas S., Elsakr M., Straus E. Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1988 Sep 15;109(6):471–473. doi: 10.7326/0003-4819-109-6-471. [DOI] [PubMed] [Google Scholar]
  27. Larner A. J., Hamilton M. I. Review article: infective complications of therapeutic gastric acid inhibition. Aliment Pharmacol Ther. 1994 Dec;8(6):579–584. doi: 10.1111/j.1365-2036.1994.tb00333.x. [DOI] [PubMed] [Google Scholar]
  28. Leach S. A., Thompson M., Hill M. Bacterially catalysed N-nitrosation reactions and their relative importance in the human stomach. Carcinogenesis. 1987 Dec;8(12):1907–1912. doi: 10.1093/carcin/8.12.1907. [DOI] [PubMed] [Google Scholar]
  29. Lipski P. S., Kelly P. J., James O. F. Bacterial contamination of the small bowel in elderly people: is it necessarily pathological? Age Ageing. 1992 Jan;21(1):5–12. doi: 10.1093/ageing/21.1.5. [DOI] [PubMed] [Google Scholar]
  30. Long J., DeSantis S., State D., White R. A., Klein S. R. The effect of antisecretagogues on gastric microflora. Arch Surg. 1983 Dec;118(12):1413–1415. doi: 10.1001/archsurg.1983.01390120041011. [DOI] [PubMed] [Google Scholar]
  31. Mauritz W., Graninger W., Schindler I., Karner J., Zadrobilek E., Sporn P. Keimflora in Magensaft und Bronchialsekret bei langzeitbeatmeten Intensivpatienten. Anaesthesist. 1985 Apr;34(4):203–207. [PubMed] [Google Scholar]
  32. Milton-Thompson G. J., Lightfoot N. F., Ahmet Z., Hunt R. H., Barnard J., Bavin P. M., Brimblecombe R. W., Darkin D. W., Moore P. J., Viney N. Intragastric acidity, bacteria, nitrite, and N-nitroso compounds before, during, and after cimetidine treatment. Lancet. 1982 May 15;1(8281):1091–1095. doi: 10.1016/s0140-6736(82)92277-2. [DOI] [PubMed] [Google Scholar]
  33. Muscroft T. J., Youngs D. J., Burdon D. W., Keighley M. R. Cimetidine is unlikely to increase formation of intragastric N-nitroso-compounds in patients taking a normal diet. Lancet. 1981 Feb 21;1(8217):408–410. doi: 10.1016/s0140-6736(81)91791-8. [DOI] [PubMed] [Google Scholar]
  34. Muscroft T. J., Youngs D., Burdon D. W., Keighley M. R. Cimetidine and the potential risk of postoperative sepsis. Br J Surg. 1981 Aug;68(8):557–559. doi: 10.1002/bjs.1800680812. [DOI] [PubMed] [Google Scholar]
  35. Pignatelli B., Richard I., Bourgade M. C., Bartsch H. Improved group determination of total N-nitroso compounds in human gastric juice by chemical denitrosation and thermal energy analysis. Analyst. 1987 Jul;112(7):945–949. doi: 10.1039/an9871200945. [DOI] [PubMed] [Google Scholar]
  36. Prewett E. J., Hudson M., Nwokolo C. U., Sawyerr A. M., Pounder R. E. Nocturnal intragastric acidity during and after a period of dosing with either ranitidine or omeprazole. Gastroenterology. 1991 Apr;100(4):873–877. doi: 10.1016/0016-5085(91)90258-m. [DOI] [PubMed] [Google Scholar]
  37. Reed P. I., Smith P. L., Haines K., House F. R., Walters C. L. Effect of cimetidine on gastric juice N-nitrosamine concentration. Lancet. 1981 Sep 12;2(8246):553–556. doi: 10.1016/s0140-6736(81)90940-5. [DOI] [PubMed] [Google Scholar]
  38. Reed P. I., Smith P. L., Haines K., House F. R., Walters C. L. Gastric juice N-nitrosamines in health and gastroduodenal disease. Lancet. 1981 Sep 12;2(8246):550–552. doi: 10.1016/s0140-6736(81)90939-9. [DOI] [PubMed] [Google Scholar]
  39. Reusser P., Zimmerli W., Scheidegger D., Marbet G. A., Buser M., Gyr K. Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients on mechanical ventilation. J Infect Dis. 1989 Sep;160(3):414–421. doi: 10.1093/infdis/160.3.414. [DOI] [PubMed] [Google Scholar]
  40. Ruddell W. S., Axon A. T., Findlay J. M., Bartholomew B. A., Hill M. J. Effect of cimetidine on the gastric bacterial flora. Lancet. 1980 Mar 29;1(8170):672–674. [PubMed] [Google Scholar]
  41. Ruddell W. S., Losowsky M. S. Severe diarrehoea due to small intestinal colonisation during cimetidine treatment. Br Med J. 1980 Jul 26;281(6235):273–273. doi: 10.1136/bmj.281.6235.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Saltzman J. R., Kowdley K. V., Pedrosa M. C., Sepe T., Golner B., Perrone G., Russell R. M. Bacterial overgrowth without clinical malabsorption in elderly hypochlorhydric subjects. Gastroenterology. 1994 Mar;106(3):615–623. doi: 10.1016/0016-5085(94)90693-9. [DOI] [PubMed] [Google Scholar]
  43. Sharma B. K., Santana I. A., Wood E. C., Walt R. P., Pereira M., Noone P., Smith P. L., Walters C. L., Pounder R. E. Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole. Br Med J (Clin Res Ed) 1984 Sep 22;289(6447):717–719. doi: 10.1136/bmj.289.6447.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sherman P., Lichtman S. Small bowel bacterial overgrowth syndrome. Dig Dis. 1987;5(3):157–171. doi: 10.1159/000171170. [DOI] [PubMed] [Google Scholar]
  45. Simon G. L., Gorbach S. L. Intestinal flora in health and disease. Gastroenterology. 1984 Jan;86(1):174–193. [PubMed] [Google Scholar]
  46. Snepar R., Poporad G. A., Romano J. M., Kobasa W. D., Kaye D. Effect of cimetidine and antacid on gastric microbial flora. Infect Immun. 1982 May;36(2):518–524. doi: 10.1128/iai.36.2.518-524.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Stockbruegger R. W. Bacterial overgrowth as a consequence of reduced gastric acidity. Scand J Gastroenterol Suppl. 1985;111:7–16. doi: 10.3109/00365528509093749. [DOI] [PubMed] [Google Scholar]
  48. Stockbruegger R. W., Cotton P. B., Menon G. G., Beilby J. O., Bartholomew B. A., Hill M. J., Walters C. L. Pernicious anaemia, intragastric bacterial overgrowth, and possible consequences. Scand J Gastroenterol. 1984 May;19(3):355–364. [PubMed] [Google Scholar]
  49. Stockbrugger R. W., Cotton P. B., Eugenides N., Bartholomew B. A., Hill M. J., Walters C. L. Intragastric nitrites, nitrosamines, and bacterial overgrowth during cimetidine treatment. Gut. 1982 Dec;23(12):1048–1054. doi: 10.1136/gut.23.12.1048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Stockbrügger R. W., Cronstedt J., Dotevall G., Hellner L., Hoffmann P., Hradsky M., Jaup B. H., Seeberg S. The intragastric milieu during gastric ulcer treatment with pirenzepine 50 mg b.i.d. or cimetidine 400 mg b.i.d. Z Gastroenterol. 1988 Nov;26(11):685–688. [PubMed] [Google Scholar]
  51. Thomas J. M., Misiewicz J. J., Cook A. R., Hill M. J., Smith P. L., Walters C. L., Forster J. K., Martin L. E., Woodings D. F. Effects of one year's treatment with ranitidine and of truncal vagotomy on gastric contents. Gut. 1987 Jun;28(6):726–738. doi: 10.1136/gut.28.6.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Thomas J. M., Misiewicz J. J., Cook A. R., Hill M. J., Smith P. L., Walters C. L., Forster J. K., Martin L. E., Woodings D. F. Effects of one year's treatment with ranitidine and of truncal vagotomy on gastric contents. Gut. 1987 Jun;28(6):726–738. doi: 10.1136/gut.28.6.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Verdu E., Viani F., Armstrong D., Fraser R., Siegrist H. H., Pignatelli B., Idström J. P., Cederberg C., Blum A. L., Fried M. Effect of omeprazole on intragastric bacterial counts, nitrates, nitrites, and N-nitroso compounds. Gut. 1994 Apr;35(4):455–460. doi: 10.1136/gut.35.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Wakabayashi K., Nagao M., Sugimura T. Mutagens and carcinogens produced by the reaction of environmental aromatic compounds with nitrite. Cancer Surv. 1989;8(2):385–399. [PubMed] [Google Scholar]
  55. Wingate D. L. Acid reduction and recurrent enteritis. Lancet. 1990 Jan 27;335(8683):222–222. doi: 10.1016/0140-6736(90)90309-s. [DOI] [PubMed] [Google Scholar]

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