Skip to main content

Advertisement

Log in

Bacterial Infection in Patients with Cirrhosis: Don’t Get Bugged to Death

  • Invited Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Bacterial infection remains a leading cause of mortality and morbidity for patients with cirrhosis, with hospitalization, alterations in the intestinal microbiota, and therapeutic drugs all implicated in its development. Bacterial infections also remain the most common precipitant of acute-on-chronic liver failure, with infection occurring as a direct consequence of the progression of this syndrome. Furthermore, recent epidemiological analyses have demonstrated that infections due to multidrug-resistant bacteria are occurring with increasing frequency in patients with cirrhosis. Despite significant advances in the understanding of the pathophysiological processes triggered by an infection in patients with cirrhosis, a demonstrable survival benefit for the sickest patients who require ICU admission has not yet occurred. Early diagnosis of infection and appropriate antimicrobial treatment is essential to ensuring optimal outcomes for these patients. This review provides an evidence-based analysis of both the current strategies for prevention and the recommended management of common bacterial infections in patients with cirrhosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Arvaniti V, D’Amico G, Fede G, et al. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010;139:1246–1256.

    PubMed  Google Scholar 

  2. Foreman MG, Mannino DM, Moss M. Cirrhosis as a risk factor for sepsis and death: analysis of the National Hospital Discharge Survey. Chest. 2003;124:1016–1020.

    PubMed  Google Scholar 

  3. Fernández J, Acevedo J, Castro M, et al. Prevalence and risk factors of infections by multiresistant bacteria in cirrhosis: a prospective study. Hepatology. 2012;55:1551–1561.

    PubMed  Google Scholar 

  4. Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology. 2005;41:422–433.

    CAS  PubMed  Google Scholar 

  5. Cazzaniga M, Dionigi E, Gobbo G, et al. The systemic inflammatory response syndrome in cirrhotic patients: relationship with their in-hospital outcome. J Hepatol. 2009;51:475–482.

    PubMed  Google Scholar 

  6. Lee Y-S, Kim B, Kamath P, et al. Outcomes of patients with cirrhosis requiring critical care in the United States. Hepatology. 2011;54:598A–599A.

    Google Scholar 

  7. Kim R, Kamath P, Shah N. Utilization and outcome of critical care in patients with cirrhosis in the US. Hepatology. 2010;52:910A–911A.

    Google Scholar 

  8. Fernández J, Acevedo J, Weist R, et al. Bacterial and fungal infections in acute-on-chronic liver failure: prevalence, characteristics and impact on prognosis. Gut. 2018;67:1870–1880.

    PubMed  Google Scholar 

  9. Fernández J, Prado V, Amoras A, et al. Multidrug-resistant bacterial infections in patients with decompensated cirrhosis and with acute-on-chronic liver failure in Europe. J Hepatol. 2019;70:398–411.

    PubMed  Google Scholar 

  10. Bonnel AR, Bunchorntavakul C, Reddy KR. Immune dysfunction and infections in patients with cirrhosis. Clin Gastroenterol Hepatol. 2011;9:727–738.

    PubMed  Google Scholar 

  11. Follo A, Llovet JM, Navasa M, et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology. 1994;20:1495–1501.

    CAS  PubMed  Google Scholar 

  12. Moreau R, Lebrec D. Acute renal failure in patients with cirrhosis: perspectives in the age of MELD. Hepatology. 2003;37:233–243.

    PubMed  Google Scholar 

  13. Ruiz-del-Arbol L, Urman J, Fernández J, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38:1210–1218.

    PubMed  Google Scholar 

  14. Fede G, Privitera G, Tomaselli T, et al. Cardiovascular dysfunction in patients with liver cirrhosis. Ann Gastroenterol. 2015;28:31–40.

    PubMed  PubMed Central  Google Scholar 

  15. Moreau R, Jalan R, Gines P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144:1426–1437.

    PubMed  Google Scholar 

  16. Wong F, Bernardi M, Balk R, et al. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club. Gut. 2005;54:718–725.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Gines P, Schrier R. Renal Failure in Cirrhosis. New Engl J Med.. 2009;361:1279–1290.

    CAS  PubMed  Google Scholar 

  18. Gustot T, Durand F, Lebrec D, et al. Severe sepsis in cirrhosis. Hepatology. 2009;50:2022–2033.

    CAS  PubMed  Google Scholar 

  19. Pascual S, Such J, Esteban A, et al. Intestinal permeability is increased in patients with advanced cirrhosis. Hepatogastroenterology. 2003;50:1482–1486.

    PubMed  Google Scholar 

  20. Scarpellini E, Valenza V, Gabrielli M, et al. Intestinal permeability in cirrhotic patients with and without spontaneous bacterial peritonitis: is the ring closed? Am J Gastroenterol. 2010;105:323–327.

    PubMed  Google Scholar 

  21. Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier. Gut.. 2016;65:330–339.

    PubMed  Google Scholar 

  22. Qin N, Yang F, Li A, et al. Alterations of the human gut microbiome in liver cirrhosis. Nature. 2014;513:59–64.

    CAS  PubMed  Google Scholar 

  23. Acevedo J, Fernández J, Prado V, et al. Relative adrenal insufficiency in decompensated cirrhosis: relationship to short-term risk of severe sepsis, hepatorenal syndrome, and death. Hepatology. 2013;58:1757–1765.

    CAS  PubMed  Google Scholar 

  24. Caly WR, Strauss E. A prospective study of bacterial infections in patients with cirrhosis. J Hepatol.. 1993;18:353–358.

    CAS  PubMed  Google Scholar 

  25. Deschênes M, Villeneuve JP. Risk factors for the development of bacterial infections in hospitalized patients with cirrhosis. Am J Gastroenterol. 1999;94:2193–2197.

    PubMed  Google Scholar 

  26. Runyon BA. Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis. Gastroenterology. 1986;91:1343–1346.

    CAS  PubMed  Google Scholar 

  27. Guarner C, Sola R, Soriano G, et al. Risk of a first community-acquired spontaneous bacterial peritonitis in cirrhotics with low ascitic fluid protein levels. Gastroenterology. 1999;117:414–419.

    CAS  PubMed  Google Scholar 

  28. Huang CH, Lin CY, Sheen IS, et al. Recurrence of spontaneous bacterial peritonitis in cirrhotic patients non-prophylactically treated with norfloxacin: serum albumin as an easy but reliable predictive factor. Liver Int. 2011;31:184–191.

    CAS  PubMed  Google Scholar 

  29. Titó L, Rimola A, Ginès P, et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Hepatology. 1988;8:27–31.

    PubMed  Google Scholar 

  30. Ginés P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990;12:716–724.

    PubMed  Google Scholar 

  31. Fernández J, Navasa M, Gómez J, et al. Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Hepatology. 2002;35:140–148.

    PubMed  Google Scholar 

  32. Bleichner G, Boulanger R, Squara P, et al. Frequency of infections in cirrhotic patients presenting with acute gastrointestinal haemorrhage. Br J Surg. 1986;73:724–726.

    CAS  PubMed  Google Scholar 

  33. Goulis J, Armonis A, Patch D, et al. Bacterial infection is independently associated with failure to control bleeding in cirrhotic patients with gastrointestinal hemorrhage. Hepatology. 1998;27:1207–1212.

    CAS  PubMed  Google Scholar 

  34. Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet. 1999;353:139–142.

    CAS  PubMed  Google Scholar 

  35. Bernard B, Grangé JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 1999;29:1655–1661.

    CAS  PubMed  Google Scholar 

  36. Jun CH, Park CH, Lee WS, et al. Antibiotic prophylaxis using third generation cephalosporins can reduce the risk of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a prospective randomized study. J Korean Med Sci. 2006;21:883–890.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Vivas S, Rodriguez M, Palacio MA, et al. Presence of bacterial infection in bleeding cirrhotic patients is independently associated with early mortality and failure to control bleeding. Dig Dis Sci. 2001;46:2752–2757. https://doi.org/10.1023/a:1012739815892.

    Article  CAS  PubMed  Google Scholar 

  38. Chavez-Tapia N, Barrientos-Gutierrez T, Tellez-Avila F, et al. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;8:CD002907.

    Google Scholar 

  39. Merli M, Lucidi C, Giannelli V, et al. Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol. 2010;8:979–985.

    PubMed  Google Scholar 

  40. Jackson MA, Goodrich JK, Maxan ME, et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749–756.

    PubMed  Google Scholar 

  41. Janarthanan S, Ditah I, Adler DG, et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis. Am J Gastroenterol. 2012;107:1001–1010.

    CAS  PubMed  Google Scholar 

  42. Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102:2047–2056.

    PubMed  Google Scholar 

  43. Liu W, Baker SS, Trinidad J, et al. Inhibition of lysosomal enzyme activities by proton pump inhibitors. J Gastroenterol. 2013;48:1343–1352.

    PubMed  Google Scholar 

  44. Laheij RJF, Sturkenboom MCJM, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292:1955–1960.

    CAS  PubMed  Google Scholar 

  45. Lombardo L, Foti M, Ruggia O, et al. Increased incidence of small intestinal bacterial overgrowth during proton pump inhibitor therapy. Clin Gastroenterol Hepatol.. 2010;8:504–508.

    PubMed  Google Scholar 

  46. Choi EJ, Lee HJ, Kim KO, et al. Association between acid suppressive therapy and spontaneous bacterial peritonitis in cirrhotic patients with ascites. Scand J Gastroenterol. 2011;46:616–620.

    PubMed  Google Scholar 

  47. Goel GA, Deshpande A, Lopez R, et al. Increased rate of spontaneous bacterial peritonitis among cirrhotic patients receiving pharmacologic acid suppression. Clin Gastroenterol Hepatol. 2012;10:422–427.

    CAS  PubMed  Google Scholar 

  48. Trikudanathan G, Israel J, Cappa J, et al. 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.

    CAS  PubMed  Google Scholar 

  49. Deshpande A, Pasupuleti V, Thota P, et al. Acid-suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. J Gastroenterol Hepatol. 2013;28:235–242.

    CAS  PubMed  Google Scholar 

  50. O’Leary J, Reddy K, Wong F, et al. Long-term use of antibiotics and proton-pump inhibitors predict development of infections in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:753–759.

    PubMed  Google Scholar 

  51. Bajaj JS, Ananthakrishnan AN, Hafeezullah M, et al. Clostridium difficile is associated with poor outcomes in patients with cirrhosis: a national and tertiary center perspective. Am J Gastroenterol. 2010;105:106–113.

    PubMed  Google Scholar 

  52. Dotson KM, Aitken SL, Sofjan A, et al. Outcomes associated with Clostridum difficile infection in patients with chronic liver disease. Epidemiol Infect. 2018;146:1101–1105.

    PubMed  PubMed Central  Google Scholar 

  53. Sersté T, Melot C, Francoz C, et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010;52:1017–1022.

    PubMed  Google Scholar 

  54. Mandorfer M, Bota S, Schwabl P, et al. Nonselective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology. 2014;146:1680–1690.

    CAS  PubMed  Google Scholar 

  55. Borzio M, Salerno F, Piantoni L, et al. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study. Dig Liver Dis. 2001;33:41–48.

    CAS  PubMed  Google Scholar 

  56. Fagiuoli S, Colli A, Bruno R, et al. Management of infections in cirrhotic patients: report of a Consensus Conference. Dig Liver Dis. 2014;46:204–212.

    PubMed  Google Scholar 

  57. Runyon BA, Canawati HN, Akriviadis EA. Optimization of ascitic fluid culture technique. Gastroenterology. 1988;95:1351–1355.

    CAS  PubMed  Google Scholar 

  58. Fernández J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol. 2012;56:S1–S12.

    PubMed  Google Scholar 

  59. Bajaj JS, O’Leary JG, Reddy KR, et al. Second infections independently increase mortality in hospitalized patients with cirrhosis: the North American consortium for the study of end-stage liver disease (NACSELD) experience. Hepatology. 2012;56:2328–2335.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Paterson DL, Ko WC, Von Gottberg A, et al. International prospective study of Klebsiella pneumoniae Bacteremia: implications of extended-spectrum beta-lactamase production in nosocomial infections. Ann Intern Med. 2004;140:26–32.

    PubMed  Google Scholar 

  61. Jalan R, Saliba F, Pavesi M, et al. Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure. J Hepatol. 2014;61:1038–1047.

    PubMed  Google Scholar 

  62. Arroyo V, Moreau R, Jalan R, et al. Acute-on-chronic liver failure: a new syndrome that will re-classify cirrhosis. J Hepatol. 2015;62:S131–S143.

    PubMed  Google Scholar 

  63. Bajaj JS, O’Leary JG, Reddy KR, et al. Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures. Hepatology. 2014;60:250–256.

    PubMed  PubMed Central  Google Scholar 

  64. Bernardi M, Moreau R, Angeli P, et al. Mechanisms of decompensation and organ failure in cirrhosis: from peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63:1272–1284.

    CAS  PubMed  Google Scholar 

  65. Albillos A, Lario M, Álvarez-Mon M. Cirrhosis-associated immune dysfunction: distinctive features and clinical relevance. J Hepatol. 2014;61:1385–1396.

    CAS  PubMed  Google Scholar 

  66. Clària J, Stauber RE, Coenraad MJ, et al. Systemic inflammation in decompensated cirrhosis: characterization and role in acute-on-chronic liver failure. Hepatology. 2016;64:1249–1264.

    PubMed  Google Scholar 

  67. Malik R, Mookerjee RP, Jalan R. Infection and inflammation in liver failure: two sides of the same coin. J Hepatol. 2009;51:426–429.

    PubMed  Google Scholar 

  68. Wasmuth HE, Kunz D, Yagmur E, et al. Patients with acute on chronic liver failure display “sepsis-like” immune paralysis. J Hepatol. 2005;42:195–201.

    CAS  PubMed  Google Scholar 

  69. Fernández J, Tandon P, Mensa J, et al. Antibiotic prophylaxis in cirrhosis: good and bad. Hepatology. 2016;63:2019–2031.

    PubMed  Google Scholar 

  70. Goldberg D, French B, Trotter J, et al. Underreporting of liver transplant waitlist removals due to death or clinical deterioration: results at four major centres. Transplantation. 2013;96:211–216.

    PubMed  Google Scholar 

  71. Finkenstedt A, Nachbaur K, Zoller H, et al. Acute-on-chronic liver failure: excellent outcomes after liver transplantation but high mortality on the wait list. Liver Transplant. 2013;19:879–886.

    Google Scholar 

  72. Hou MC, Lin HC, Te Liu T, et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology. 2004;39:746–753.

    CAS  PubMed  Google Scholar 

  73. Soriano G, Guarner C, Tomás A, et al. Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. Gastroenterology. 1992;103:1267–1272.

    CAS  PubMed  Google Scholar 

  74. Fernández J, Ruiz del Arbol L, Gómez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology. 2006;131:1049–1056.

    PubMed  Google Scholar 

  75. Fernández J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133:818–824.

    PubMed  Google Scholar 

  76. Saab S, Hernandez JC, Chi AC, et al. Oral antibiotic prophylaxis reduces spontaneous bacterial peritonitis occurrence and improves short-term survival in cirrhosis: a meta-analysis. Am J Gastroenterol. 2009;104:993–1001.

    CAS  PubMed  Google Scholar 

  77. European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol. 2010;53:397–417.

    Google Scholar 

  78. Terg R, Fassio E, Guevara M, et al. Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: a randomized, placebo-controlled study. J Hepatol. 2008;48:774–779.

    CAS  PubMed  Google Scholar 

  79. Grange JD, Roulot D, Pelletier G, et al. Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial. J Hepatol. 1998;29:430–436.

    CAS  PubMed  Google Scholar 

  80. Novella M, Sola R, Soriano G, et al. Continuous versus inpatient prophylaxis of the first episode of spontaneous bacterial peritonitis with norfloxacin. Hepatology. 1997;25:532–536.

    CAS  PubMed  Google Scholar 

  81. Lucidi C, Giannelli V, Giusto M, et al. High Prevalence of MDR infections in cirrhotic patients who have had contact with the healthcare system (Abstract 1857). Hepatology. 2011;54:1236A.

    Google Scholar 

  82. Ariza X, Castellote J, Lora-Tamayo J, et al. Risk factors for resistance to ceftriaxone and its impact on mortality in community, healthcare and nosocomial spontaneous bacterial peritonitis. J Hepatol. 2012;56:825–832.

    CAS  PubMed  Google Scholar 

  83. Piano S, Fasolato S, Salinas F, et al. The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: results of a randomized, controlled clinical trial. Hepatology. 2016;63:1299–1309.

    CAS  PubMed  Google Scholar 

  84. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60:1310–1324.

    PubMed  Google Scholar 

  85. European Association for the Study of the Liver. EASL clinical practice guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–460.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mary D. Cannon.

Ethics declarations

Conflict of interest

The authors have no disclosures pertinent to this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cannon, M.D., Martin, P. & Carrion, A.F. Bacterial Infection in Patients with Cirrhosis: Don’t Get Bugged to Death. Dig Dis Sci 65, 31–37 (2020). https://doi.org/10.1007/s10620-019-05943-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-019-05943-6

Keywords

Navigation