Digestive Diseases and Sciences

, Volume 53, Issue 2, pp 394–398 | Cite as

Association between Proton Pump Inhibitor Use and Spontaneous Bacterial Peritonitis

  • Mical S. Campbell
  • Keith Obstein
  • K. Rajender Reddy
  • Yu-Xiao YangEmail author
Original Paper


Proton pump inhibitors (PPIs) increase enteric bacterial colonization, overgrowth, and translocation, all effects which might predispose to spontaneous bacterial peritonitis. We investigated whether PPI usage is associated with spontaneous bacterial peritonitis. Our retrospective case-control study included 116 consecutive cirrhotic patients with ascites who underwent diagnostic paracentesis upon hospital admission (2002–2005). Spontaneous bacterial peritonitis was defined as paracentesis yielding ≥250 polymorphonuclear leukocytes/ml. We performed logistic regression to determine the risk of spontaneous bacterial peritonitis by PPI usage. Of the 116 subjects, 32 had spontaneous bacterial peritonitis. Patient characteristics were similar between groups with and without infection, with the exception of the Model for End-Stage Liver Disease score (median: 23 and 18, respectively; P = 0.002). Crude and adjusted odds ratios for the development of spontaneous bacterial peritonitis by exposure to PPIs were 1.22 (95% confidence interval: 0.52–2.87) and 1.05 (0.43–2.57), respectively. In conclusion, we did not find a positive association between PPI use and spontaneous bacterial peritonitis.


Acid suppression Ascites Cirrhosis Heartburn Proton pump inhibitors Spontaneous bacterial peritonitis) 



Histamine 2 receptor antagonist


Model for end-stage liver disease


Polymorphonuclear leukocytes


Proton pump inhibitor


Spontaneous bacterial peritonitis


  1. 1.
    Pinzello G, Simonetti RG, Craxi A et al (1993) Spontaneous bacterial peritonitis: a prospective investigation in predominantly nonalcoholic cirrhotic patients. Hepatology 3:545–549Google Scholar
  2. 2.
    Runyon BA, Squier SU, Borzio M (1994) Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol 21:792–796PubMedCrossRefGoogle Scholar
  3. 3.
    Cirera I, Bauer TM, Navasa M et al (2001) Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 34:32–37PubMedCrossRefGoogle Scholar
  4. 4.
    Garcia-Tsao G, Albillos A, Barden GE et al (1993) Bacterial translocation in acute and chronic portal hypertension. Hepatology 17:1081–1085PubMedCrossRefGoogle Scholar
  5. 5.
    Llovet JM, Bartoli R, March F et al (1998) Translocated intestinal bacterial cause spontaneous bacterial peritonitis in cirrhotic rats: molecular epidemiologic evidence. J Hepatol 28:307–313PubMedCrossRefGoogle Scholar
  6. 6.
    Guarner C, Runyon BA, Youns S et al (1997) Intestinal bacterial overgrowth and bacterial translocation in an experimental model of cirrhosis in rats. J Hepatol 26:1372–1378PubMedCrossRefGoogle Scholar
  7. 7.
    Fiuza C, Salcedo M, Clemente G et al. (2000) In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease. J Infect Dis 182:526–533PubMedCrossRefGoogle Scholar
  8. 8.
    Runyon BA (1988) Patients with deficient ascetic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis. Hepatology 8:632–635PubMedCrossRefGoogle Scholar
  9. 9.
    Bauer TM, Steinbruckner B, Brinkmann FE et al (2001) Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol 96:2962–2967PubMedCrossRefGoogle Scholar
  10. 10.
    Thorens J, Froehlich F, Schwizer W et al (1996) Bacterial overgrowth during treatment with omeprazole compared with cimetidine. Gut 39:54–59PubMedCrossRefGoogle Scholar
  11. 11.
    Prod’hom G, Leuenberger P, Koerfer J, Blum A, Chiolero R, Schaller MD, Perret C, Spinnler O, Blondel J, Siegrist H, Saghafi L, Blanc D, Francioli P (1994) Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomized controlled trial. Ann Intern Med 120:653–662PubMedGoogle Scholar
  12. 12.
    Laheij R, Sturkenboom MC, Hassing R, Dieleman J, Stricker BH, Jansen JB (2004) Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA 292:1955–1960PubMedCrossRefGoogle Scholar
  13. 13.
    Dial S, Delaney JAC, Barkun AN, Suissa S (2005) Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 294:2989–2995PubMedCrossRefGoogle Scholar
  14. 14.
    Dial S, Alrasadi K, Manoukian C et al. (2004) Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. Can Med Assoc J 171:33–38CrossRefGoogle Scholar
  15. 15.
    Cunningham R, Dale B, Undy B et al. (2003) Proton pump inhibitors as a risk factor for Clostridium difficile diarrhoea. J Hosp Infect 54:243–245PubMedCrossRefGoogle Scholar
  16. 16.
    Loo VG, Poirier L, Miller MA et al. (2005) A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med 353:2442–2449PubMedCrossRefGoogle Scholar
  17. 17.
    Shah S, Lewis A, Leopold D et al. (2000) Gastric acid suppression does not promote clostridial diarrhoea in the elderly. Q J Med 93:175–178Google Scholar
  18. 18.
    Parkman HP, Urbain JL, Knight LC, Brown KL, Trate DM, Miller MA, Maurer AH, Fisher RS (1998) Effect of gastric acid suppressants on human gastric motility. Gut 42:243–250PubMedCrossRefGoogle Scholar
  19. 19.
    Armbrecht U, Dotevall G, Stockbrugger RW (1987) The effect of gastric secretion on orocoecal transit time measured with the hydrogen (H2) breath test. Z Gastroenterol 24:145–150Google Scholar
  20. 20.
    Yoshida N, Yoshikawa T, Tanaka Y, Fujita N, Kassai K, Naito Y, Kondo M (2000) A new mechanism for anti-inflammatory actions of proton pump inhibitors inhibitory effects on neutrophil–endothelial cell interactions. Aliment Pharmacol Ther 14:74–81PubMedCrossRefGoogle Scholar
  21. 21.
    Zedtwitz-Liebenstein K, Wenisch C, Patruta S, Parschalk B, Daxbock F, Graninger W (2002) Omeprazole treatment diminished intra- and extracellular neutrophil reactive oxygen production and bactericidal activity. Crit Care Med 30:1118–1122PubMedCrossRefGoogle Scholar
  22. 22.
    Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129:125–137PubMedGoogle Scholar
  23. 23.
    Runyon BA, Canawati HN, Akriviadis EA (1988) Optimization of ascitic fluid culture technique. Gastroenterology 95:1351–1355PubMedGoogle Scholar
  24. 24.
    Runyon BA, Antillon MR, Akriviadis EA, McHutchison JG (1990) Bedside inoculation of blood culture bottles is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis. J Clin Microbiol 28:2811–2812PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Mical S. Campbell
    • 1
    • 3
  • Keith Obstein
    • 1
  • K. Rajender Reddy
    • 1
    • 3
  • Yu-Xiao Yang
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Center for Clinical Epidemiology and BiostatisticsUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of GastroenterologyHospital of the University of PennsylvaniaPhiladelphiaUSA

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