0 item
0 item
Login
Help

Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or OpenAthens)

For the academic login, please select your organization on the next page. You will be redirected to verify your credentials.

OpenAthens/Shibboleth

Journal Menu

Original Article

Open Access Gateway

Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients Using Proton Pump Inhibitors

Elzouki A.-N.a,b · Neffati N.a · Rasoul F.A.a · Abdallah A.a · Othman M.a · Waness A.a

Author affiliations

aDepartment of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
bWeill Cornell Medical College, Doha, Qatar

Corresponding Author

Prof. Abdel-Naser Elzouki

Department of Medicine, Hamad General Hospital

Hamad Medical Corporation, P.O. Box 3050

Doha 3050 (Qatar)

E-Mail nelzouki_1999@yahoo.com

Keywords: Acid suppressive medicationsBacterial infectionInfectionLiver cirrhosisQatar

Related Articles for ""
GE Port J Gastroenterol 2019;26:83–89
https://doi.org/10.1159/000487963

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Abstract

Background: The association between bacterial infections and proton pump inhibitors (PPIs) has recently been studied with debatable results. Aim: The aim of this study was to investigate the relationship between PPIs and the development of spontaneous bacterial peritonitis (SBP) or other bacterial infections in cirrhotic patients. Materials and Methods: Consecutive cirrhotic patients hospitalized from 2007 through 2012 to Hamad General Hospital–, Doha, Qatar, were enrolled and classified as PPI users or non-users according to PPI consumption in the 90 days prior to hospitalization. Cirrhosis was clinically diagnosed by a combination of physical, biochemical, radiological, and endoscopic findings, or by liver biopsy. Results: A total of 333 patients were included in this study, of whom 171 (51.4%) used PPIs and 162 (48.6%) did not use PPIs. PPI users were significantly older in age (p = 0.001). There was no statistical difference between the 2 groups in sex distribution and etiology of cirrhosis (p > 0.05 for both parameters). PPI users had a significantly higher incidence of overall bacterial infection (38%) than non-PPI users (13.6%), p = 0.0001. Statistical significance is observed specifically for SBP and chest infection (p = 0.0006 and p = 0.01, respectively). In multivariate analysis, older age (> 60 years; OR = 1.246, 95% CI 1.021–08.486; p = 0.02), and PPI use (OR = 2.149, 95% CI 1.124–06.188; p = 0.01) were independent predicting factors for SBP and overall bacterial infection. Conclusion: The present study shows that PPI use, as well as older age (> 60 years), was an independent predicting factor for the development of overall infection and SBP in hospitalized cirrhotic patients. Unless it is indicated, PPI therapy should be avoided in this group of patients, particularly in those older than 60 years of age.

© 2018 Sociedade Portuguesa de Gastrenterologia Published by S. Karger AG, Basel

Risco Aumentado de Peritonite Bacteriana Espontânea em Doentes Cirróticos Medicados com Inibidores da Bomba de Protões

Palavras Chave

Medicações ácido-supressoras · Infeção bacteriana · Infeção · Cirrose hepática · Qatar ·

Resumo

Introdução: A associação entre infeções bacterianas e os Inibidores da bomba de protões (IBPs) tem vindo a ser estudada com resultados discutíveis. Objetivo: O objetivo deste estudo foi investigar a relação entre IBPs e o desenvolvimento de peritonite bacteriana espontânea (PBE) ou outras infeções bacterianas em doentes cirróticos. Material e Métodos: Doentes consecutivos com cirrose hospitalizados entre 2007 e 2012 no Hamad General Hospital-Qatar foram selecionados e classificados como utilizadores ou não utilizadores de IBPs de acordo com o seu consumo nos 90 dias prévios ao internamento. A cirrose foi clinicamente diagnosticada por uma combinação de achados no exame físico, no estudo bioquímico, radiológico e endoscópico; ou por biopsia hepática. Resultados: Um total de 333 doentes foi incluído neste estudo, 171 (51.4%) medicados com IBPs e 162 não (48.6%). Os utilizadores de IBPs eram significativamente mais velhos (p = 0.001). Não se observaram diferenças estatísticas entre os dois grupos no que se refere ao sexo ou etiologia da cirrose (p e; 0.05 para os dois parâmetros). A incidência global de infeções bacterianas foi significativamente superior nos utilizadores de IBPs (38%) do que nos não utilizadores (13.6%), p = 0.0001. O significado estatístico desta diferença foi observado especificamente para a PBE e para as infeções pulmonares (p = 0.0006 e p = 0.01, respetivamente). Na análise multivariada, a idade superior a 60 anos (OR = 1.246, 95% CI 1.021–08.486; p = 0.02), e a utilização de IBPs (OR = 2.149, 95% CI 1.124–06.188; p = 0.01) foram fatores preditivos independentes para PBE e para infeção bacteriana no global. Conclusão: Este estudo mostra que a utilização de IBPs, assim como a idade superior a 60 anos, são fatores preditivos independentes para o desenvolvimento de infeções bacterianas no global e para PBE nos doentes cirróticos hospitalizados. A não ser que esteja especificamente indicado a utilização de IBPs deve ser evitada neste grupo de doentes, particularmente naqueles com idade superior a 60 anos.



Related Articles:

References

  1. Durand C, Willett KC, Desilets AR: Proton pump inhibitor use in hospitalized patients: is overutilization becoming a problem? Clin Med Insights Gastroenterol 2012; 5: 65–76.
    External Resources
  2. Rotman SR, Bishop TF: Proton pump inhibitor use in the U.S. ambulatory setting, 2002–2009. PLoS One 2013; 8:e56060.
    External Resources
  3. Lewis JR, Barre D, Zhu K, Ivey KL, Lim EM, Hughes J, Prince RL: Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study. J Bone Miner Res 2014; 29: 2489–2497.
    External Resources
  4. Thomson AB, Sauve MD, Kassam N, Kamitakahara H: Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 2010; 16: 2323–2330.
    External Resources
  5. Miano TA, Reichert MG, Houle TT, MacGregor DA, Kincaid EH, Bowton DL: Nosocomial pneumonia risk and stress ulcer prophylaxis: a comparison of pantoprazole versus ranitidine in cardiothoracic surgery patients. Chest 2009; 136: 440–447.
    External Resources
  6. Barletta JF, Sclar DA: Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care 2014; 18: 714.
    External Resources
  7. O’leary JG, Reddy KR, Wong F, Kamath PS, Patton HM, Biggins SW: Long-term use of antibiotics and proton-pump imhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2015; 13: 753–759.
    External Resources
  8. Bajaj SC, O’leary JG, Reddy KR, Wong F, Olson JC, Subramanian RM, Brown G, et al: Second infections independently increase mortality in hospitalized patients with cirrhosis. North American consortium for the study of end-stage of liver disease (NACSELD) experience. Hepatology 2012: 56: 2328–2335.
    External Resources
  9. Churpek MM, Snyder A, Sokol S, Pettit NN, Edelson DP: Investigating the impact of different suspicion of infection criteria on the accuracy of quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores. Crit Care Med 2017; 45: 1805–1812.
    External Resources
  10. Agastya G, West BC, Callahan JM: Omeprazole inhibits phagocytosis and acidification of phagolysosomes of normal human neutrophils in vitro. Immunopharmacol Immunotoxicol 2000; 22: 357–372.
    External Resources
  11. Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxböck F, Graninger W: Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med 2002; 30: 1118–1122.
    External Resources
  12. Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M: Immune dysfunction in cirrhosis. World J Gastroenterol 2014; 20: 2564–2577.
    External Resources
  13. Lagadinou M, Solomou EE, Velissaris D, Theodorou GL, Karakatza M, Gogos CA: Alterations in T-lymphocyte subpopulations in patients with complicated liver cirrhosis. Diagn Microbiol Infect Dis 2013; 75: 348–356.
    External Resources
  14. O’Brien AJ, Fullerton JN, Massey KA, Auld G, Sewell G, James S, Newson J, et al: Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014; 20: 518–523.
    External Resources
  15. Lin CY, Tsai IF, Ho YP, Huang CT, Lin YC, Lin CJ, Tseng SC, et al: Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 2007; 46: 816–826.
    External Resources
  16. Garcia-Martinez I, Francés R, Zapater P, Giménez P, Gómez-Hurtado I, Moratalla A, Lozano-Ruiz B, et al: Use of proton pump inhibitors decrease cellular oxidative burst in patients with decompensated cirrhosis. J Gastroenterol Hepatol 2015; 30: 147–154.
    External Resources
  17. Min WY, Lim KS, Min BH, Gwak GY, Paik YH, Choi MS, Lee JH, et al: Proton pump inhibitor use significantly increases the risk of spontaneous bacteria peritonitis in 1965 patients with cirrhosis and ascites: a propensity score matched cohort study. Aliment Pharmacol Ther 2014; 40: 695–704.
    External Resources
  18. von Vlerken LG, Huisman EJ, van Hoek B, Renooij W, Felix W, Siersema PD, van Erpecum KJ: Bacterial infections in cirrhosis: role of proton pump inhibitors and intestinal permeability. Eur J Clin Invest 2012; 42: 760–767.
    External Resources
  19. Chang SS, Lai CC, Lee MT, Lee YC, Tsai YW, Hsu WT, Lee CC: Risk of spontaneous bacterial peritonitis associated with gastric acid suppression. Medicine (Baltimore) 2015; 94:e944.
    External Resources
  20. Parkman HP, Urbain JL, Knight LC, Brown KL, Trate DM, Miller MA, Maurer AH, et al: Effect of gastric acid suppressant on human gastric motility. Gut 1998; 42: 2043–2050.
    External Resources
  21. Campbell MS, Obstein K, Reddy KR, Yang YX: Association between proton pump inhibitor use and spontaneous bacterial peritonitis. Dig Dis Sci 2008; 53: 394–398.
    External Resources
  22. Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Summereder C, Hagmann M, et al: Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites. PLoS One 2014; 9:e110503.
    External Resources
  23. Terg R, Casciato P, Garbe C, Cartier M, Stieben T, Mendizabal M, Niveyro C, et al: Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol 2015; 62: 1056–1060.
    External Resources
  24. Kim JH, Lim KS, Min YW, Lee H, Min BH, Rhee PL, Kim JJ, et al: Proton pump inhibitors do not increase the risk for recurrent spontaneous bacterial peritonitis in patients with cirrhosis. J Gastroenterol Hepatol 2017; 32: 1064–1070.
    External Resources
  25. Miozzo SAS, John JA, Appel-da-Silva MC, Dossin IA, Tovo CV, Mattos AA. Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis. World J Hepatol 2017; 9: 1278–1285.
    External Resources
  26. Trikudanathan G, Israel J, Cappa J, O’Sullivan DM: Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients – a systematic review and meta-analysis. Int J Clin Pract 2011; 65: 674–678.
    External Resources
  27. Deshpande A, Pasupuleti V, Thota P, Pant C, Mapara S, Hassan S, Rolston DD, et al: Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol 2013; 28: 235–242.
    External Resources
  28. Xu HB, Wang HD, Li CH, Ye S, Dong MS, Xia QJ, Zhang AQ, et al: Proton pump inhibitor use and risk of spontaneous bacteria peritonitisin cirrhotic patiens: a systematic review and meta analysis. Genet Molecular Research 2015; 14: 7490–7501.
    External Resources
  29. Kwon JH, Koh SJ, Kim W, Jung YJ, Kim JW, Kim BG, Lee KL, et al: Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis. J Gastroenterol Hepatol 2014; 29: 775–781.
    External Resources
  30. Dam G, Vilstrup H, Watson H, Jepsen P: Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology 2016; 64: 1265–1272.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: November 28, 2017
Accepted: February 23, 2018
Published online: June 08, 2018
Issue release date: March - April

Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 4

ISSN: 2341-4545 (Print)
eISSN: 2387-1954 (Online)

For additional information: https://www.karger.com/PJG

References

  1. Durand C, Willett KC, Desilets AR: Proton pump inhibitor use in hospitalized patients: is overutilization becoming a problem? Clin Med Insights Gastroenterol 2012; 5: 65–76.
    External Resources
  2. Rotman SR, Bishop TF: Proton pump inhibitor use in the U.S. ambulatory setting, 2002–2009. PLoS One 2013; 8:e56060.
    External Resources
  3. Lewis JR, Barre D, Zhu K, Ivey KL, Lim EM, Hughes J, Prince RL: Long-term proton pump inhibitor therapy and falls and fractures in elderly women: a prospective cohort study. J Bone Miner Res 2014; 29: 2489–2497.
    External Resources
  4. Thomson AB, Sauve MD, Kassam N, Kamitakahara H: Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 2010; 16: 2323–2330.
    External Resources
  5. Miano TA, Reichert MG, Houle TT, MacGregor DA, Kincaid EH, Bowton DL: Nosocomial pneumonia risk and stress ulcer prophylaxis: a comparison of pantoprazole versus ranitidine in cardiothoracic surgery patients. Chest 2009; 136: 440–447.
    External Resources
  6. Barletta JF, Sclar DA: Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients. Crit Care 2014; 18: 714.
    External Resources
  7. O’leary JG, Reddy KR, Wong F, Kamath PS, Patton HM, Biggins SW: Long-term use of antibiotics and proton-pump imhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol 2015; 13: 753–759.
    External Resources
  8. Bajaj SC, O’leary JG, Reddy KR, Wong F, Olson JC, Subramanian RM, Brown G, et al: Second infections independently increase mortality in hospitalized patients with cirrhosis. North American consortium for the study of end-stage of liver disease (NACSELD) experience. Hepatology 2012: 56: 2328–2335.
    External Resources
  9. Churpek MM, Snyder A, Sokol S, Pettit NN, Edelson DP: Investigating the impact of different suspicion of infection criteria on the accuracy of quick sepsis-related organ failure assessment, systemic inflammatory response syndrome, and early warning scores. Crit Care Med 2017; 45: 1805–1812.
    External Resources
  10. Agastya G, West BC, Callahan JM: Omeprazole inhibits phagocytosis and acidification of phagolysosomes of normal human neutrophils in vitro. Immunopharmacol Immunotoxicol 2000; 22: 357–372.
    External Resources
  11. Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxböck F, Graninger W: Omeprazole treatment diminishes intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med 2002; 30: 1118–1122.
    External Resources
  12. Sipeki N, Antal-Szalmas P, Lakatos PL, Papp M: Immune dysfunction in cirrhosis. World J Gastroenterol 2014; 20: 2564–2577.
    External Resources
  13. Lagadinou M, Solomou EE, Velissaris D, Theodorou GL, Karakatza M, Gogos CA: Alterations in T-lymphocyte subpopulations in patients with complicated liver cirrhosis. Diagn Microbiol Infect Dis 2013; 75: 348–356.
    External Resources
  14. O’Brien AJ, Fullerton JN, Massey KA, Auld G, Sewell G, James S, Newson J, et al: Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nat Med 2014; 20: 518–523.
    External Resources
  15. Lin CY, Tsai IF, Ho YP, Huang CT, Lin YC, Lin CJ, Tseng SC, et al: Endotoxemia contributes to the immune paralysis in patients with cirrhosis. J Hepatol 2007; 46: 816–826.
    External Resources
  16. Garcia-Martinez I, Francés R, Zapater P, Giménez P, Gómez-Hurtado I, Moratalla A, Lozano-Ruiz B, et al: Use of proton pump inhibitors decrease cellular oxidative burst in patients with decompensated cirrhosis. J Gastroenterol Hepatol 2015; 30: 147–154.
    External Resources
  17. Min WY, Lim KS, Min BH, Gwak GY, Paik YH, Choi MS, Lee JH, et al: Proton pump inhibitor use significantly increases the risk of spontaneous bacteria peritonitis in 1965 patients with cirrhosis and ascites: a propensity score matched cohort study. Aliment Pharmacol Ther 2014; 40: 695–704.
    External Resources
  18. von Vlerken LG, Huisman EJ, van Hoek B, Renooij W, Felix W, Siersema PD, van Erpecum KJ: Bacterial infections in cirrhosis: role of proton pump inhibitors and intestinal permeability. Eur J Clin Invest 2012; 42: 760–767.
    External Resources
  19. Chang SS, Lai CC, Lee MT, Lee YC, Tsai YW, Hsu WT, Lee CC: Risk of spontaneous bacterial peritonitis associated with gastric acid suppression. Medicine (Baltimore) 2015; 94:e944.
    External Resources
  20. Parkman HP, Urbain JL, Knight LC, Brown KL, Trate DM, Miller MA, Maurer AH, et al: Effect of gastric acid suppressant on human gastric motility. Gut 1998; 42: 2043–2050.
    External Resources
  21. Campbell MS, Obstein K, Reddy KR, Yang YX: Association between proton pump inhibitor use and spontaneous bacterial peritonitis. Dig Dis Sci 2008; 53: 394–398.
    External Resources
  22. Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Summereder C, Hagmann M, et al: Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites. PLoS One 2014; 9:e110503.
    External Resources
  23. Terg R, Casciato P, Garbe C, Cartier M, Stieben T, Mendizabal M, Niveyro C, et al: Proton pump inhibitor therapy does not increase the incidence of spontaneous bacterial peritonitis in cirrhosis: a multicenter prospective study. J Hepatol 2015; 62: 1056–1060.
    External Resources
  24. Kim JH, Lim KS, Min YW, Lee H, Min BH, Rhee PL, Kim JJ, et al: Proton pump inhibitors do not increase the risk for recurrent spontaneous bacterial peritonitis in patients with cirrhosis. J Gastroenterol Hepatol 2017; 32: 1064–1070.
    External Resources
  25. Miozzo SAS, John JA, Appel-da-Silva MC, Dossin IA, Tovo CV, Mattos AA. Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis. World J Hepatol 2017; 9: 1278–1285.
    External Resources
  26. Trikudanathan G, Israel J, Cappa J, O’Sullivan DM: Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients – a systematic review and meta-analysis. Int J Clin Pract 2011; 65: 674–678.
    External Resources
  27. Deshpande A, Pasupuleti V, Thota P, Pant C, Mapara S, Hassan S, Rolston DD, et al: Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol 2013; 28: 235–242.
    External Resources
  28. Xu HB, Wang HD, Li CH, Ye S, Dong MS, Xia QJ, Zhang AQ, et al: Proton pump inhibitor use and risk of spontaneous bacteria peritonitisin cirrhotic patiens: a systematic review and meta analysis. Genet Molecular Research 2015; 14: 7490–7501.
    External Resources
  29. Kwon JH, Koh SJ, Kim W, Jung YJ, Kim JW, Kim BG, Lee KL, et al: Mortality associated with proton pump inhibitors in cirrhotic patients with spontaneous bacterial peritonitis. J Gastroenterol Hepatol 2014; 29: 775–781.
    External Resources
  30. Dam G, Vilstrup H, Watson H, Jepsen P: Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology 2016; 64: 1265–1272.
    External Resources
Tables
Thumbnail
Thumbnail
Thumbnail
Thumbnail

Open Access License / Drug Dosage / Disclaimer

This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Top

Article Tools
Article Details

2019, Vol.26, No. 2

March - April

Open Access Gateway

previous Article next

Recommend This
Open Access Gateway