Pathogenesis of spontaneous bacterial peritonitis
- Bruce A Runyon, MD
Bruce A Runyon, MD
- Section Editor — Cirrhosis and Its Complications
- Clinical Professor of Medicine
- University of New Mexico, Division of Gastroenterology and Hepatology
- Special Hepatology Consultant to the Indian Health Service
- Northern Navajo Medical Center, Shiprock, New Mexico
Spontaneous bacterial peritonitis (SBP) is defined as an ascitic fluid infection without an evident intra-abdominal surgically treatable source . The presence of infection is documented by a positive ascitic fluid bacterial culture and an elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count (≥250 cells/mm3). The absolute PMN count is calculated by multiplying the total white blood cell count (or total "nucleated cell" count) by the percentage of PMNs in the differential. The cell count and differential are performed manually without formal quality control. The accuracy of these tests is totally dependent upon the skill and interest of the medical technologist. (See "Spontaneous bacterial peritonitis in adults: Diagnosis".)
Our current understanding of the pathogenesis of SBP will be reviewed here. The clinical manifestations, diagnosis, and treatment of SBP are discussed separately. (See "Spontaneous bacterial peritonitis in adults: Clinical manifestations" and "Spontaneous bacterial peritonitis in adults: Diagnosis" and "Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis".)
When the phrase spontaneous bacterial peritonitis was coined in 1964, the descriptor "spontaneous" was used because the pathogenesis of the infection was not apparent . Over the past decades, this void of information has been at least partially filled  (figure 1).
Microbiology and bacterial entry into ascites — One of the early steps in the development of SBP is a disturbance in gut flora with overgrowth and extraintestinal dissemination of a specific organism, most commonly Escherichia coli (table 1) [3,4]. Cirrhosis predisposes to the development of bacterial overgrowth, possibly because of altered small intestinal motility , and the presence of hypochlorhydria due to use of proton pump inhibitors . In addition, patients with cirrhosis may have increased intestinal permeability .
However, the role of bacterial overgrowth in the pathogenesis of SBP remains unsettled. In one study, small bowel motility and bacterial overgrowth were compared in 20 patients with cirrhosis and a history of SBP and 20 patients with cirrhosis without a history of SBP . The prevalence of bacterial overgrowth was higher in the patients with a history of SBP (70 versus 20 percent); these patients also exhibited more severe small intestinal motility disturbances. In contrast, in another study, the presence of bacterial overgrowth was not associated with the development of SBP . (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- CONN HO. SPONTANEOUS PERITONITIS AND BACTEREMIA IN LAENNEC'S CIRRHOSIS CAUSED BY ENTERIC ORGANISMS. A RELATIVELY COMMON BUT RARELY RECOGNIZED SYNDROME. Ann Intern Med 1964; 60:568.
- Sheer TA, Runyon BA. Spontaneous bacterial peritonitis. Dig Dis 2005; 23:39.
- Guarner C, Runyon BA, Young S, et al. Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites. J Hepatol 1997; 26:1372.
- Runyon BA, Squier S, Borzio M. Translocation of gut bacteria in rats with cirrhosis to mesenteric lymph nodes partially explains the pathogenesis of spontaneous bacterial peritonitis. J Hepatol 1994; 21:792.
- Madrid AM, Cumsille F, Defilippi C. Altered small bowel motility in patients with liver cirrhosis depends on severity of liver disease. Dig Dis Sci 1997; 42:738.
- Sánchez E, Soriano G, Mirelis B, et al. Effect of long-term acid gastric inhibition on bacterial translocation in cirrhotic rats. Eur J Gastroenterol Hepatol 2015; 27:570.
- 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.
- Chang CS, Chen GH, Lien HC, Yeh HZ. Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology 1998; 28:1187.
- Bauer TM, Steinbrückner B, Brinkmann FE, et al. Small intestinal bacterial overgrowth in patients with cirrhosis: prevalence and relation with spontaneous bacterial peritonitis. Am J Gastroenterol 2001; 96:2962.
- Guarner C, Runyon BA. Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management. Gastroenterologist 1995; 3:311.
- Casafont F, Sánchez E, Martín L, et al. Influence of malnutrition on the prevalence of bacterial translocation and spontaneous bacterial peritonitis in experimental cirrhosis in rats. Hepatology 1997; 25:1334.
- Cirera I, Bauer TM, Navasa M, et al. Bacterial translocation of enteric organisms in patients with cirrhosis. J Hepatol 2001; 34:32.
- Runyon BA. Early events in spontaneous bacterial peritonitis. Gut 2004; 53:782.
- Wiest R, Garcia-Tsao G. Bacterial translocation (BT) in cirrhosis. Hepatology 2005; 41:422.
- Such J, Francés R, Muñoz C, et al. Detection and identification of bacterial DNA in patients with cirrhosis and culture-negative, nonneutrocytic ascites. Hepatology 2002; 36:135.
- Such J, Hillebrand DJ, Guarner C, et al. Tumor necrosis factor-alpha, interleukin-6, and nitric oxide in sterile ascitic fluid and serum from patients with cirrhosis who subsequently develop ascitic fluid infection. Dig Dis Sci 2001; 46:2360.
- Zapater P, Francés R, González-Navajas JM, et al. Serum and ascitic fluid bacterial DNA: a new independent prognostic factor in noninfected patients with cirrhosis. Hepatology 2008; 48:1924.
- Bajaj JS, Zadvornova Y, Heuman DM, et al. Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009; 104:1130.
- Sanchez E, Soriano G, Mirelis B. Effect of long-term inhibition of acid gastric secretion on gastric pH and on bacterial translocation in cirrhotic rats (abstract). Hepatology 2007; 46 Suppl:604A.
- Garcia-Martinez I, Francés R, Zapater P, et al. Use of proton pump inhibitors decrease cellular oxidative burst in patients with decompensated cirrhosis. J Gastroenterol Hepatol 2015; 30:147.
- Ho H, Zuckerman MJ, Ho TK, et al. Prevalence of associated infections in community-acquired spontaneous bacterial peritonitis. Am J Gastroenterol 1996; 91:735.
- Runyon BA, Morrissey RL, Hoefs JC, Wyle FA. Opsonic activity of human ascitic fluid: a potentially important protective mechanism against spontaneous bacterial peritonitis. Hepatology 1985; 5:634.
- Dunn DL, Barke RA, Knight NB, et al. Role of resident macrophages, peripheral neutrophils, and translymphatic absorption in bacterial clearance from the peritoneal cavity. Infect Immun 1985; 49:257.
- Runyon BA. Bacterial infections in patients with cirrhosis. J Hepatol 1993; 18:271.
- Runyon BA. Low-protein-concentration ascitic fluid is predisposed to spontaneous bacterial peritonitis. Gastroenterology 1986; 91:1343.
- Runyon BA. Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis. Hepatology 1988; 8:632.
- Laffi G, Carloni V, Baldi E, et al. Impaired superoxide anion, platelet-activating factor, and leukotriene B4 synthesis by neutrophils in cirrhosis. Gastroenterology 1993; 105:170.
- Rimola A, Soto R, Bory F, et al. Reticuloendothelial system phagocytic activity in cirrhosis and its relation to bacterial infections and prognosis. Hepatology 1984; 4:53.
- Tritto G, Frances R, Shah N. Plasma from stable patients with cirrhosis transmits severe neutrophil phagocytic dysfunction which is independent of the presence of bacterial DNA and associated with increased expression of TLR-4. Hepatology 2009; 50:311A.
- Titó L, Rimola A, Ginès P, et al. Recurrence of spontaneous bacterial peritonitis in cirrhosis: frequency and predictive factors. Hepatology 1988; 8:27.
- Llach J, Rimola A, Navasa M, et al. Incidence and predictive factors of first episode of spontaneous bacterial peritonitis in cirrhosis with ascites: relevance of ascitic fluid protein concentration. Hepatology 1992; 16:724.
- Andreu M, Sola R, Sitges-Serra A, et al. Risk factors for spontaneous bacterial peritonitis in cirrhotic patients with ascites. Gastroenterology 1993; 104:1133.
- Rimola A, Bory F, Teres J, et al. Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage. Hepatology 1985; 5:463.
- 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.
- Min YW, Lim KS, Min BH, et al. Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in 1965 patients with cirrhosis and ascites: a propensity score matched cohort study. Aliment Pharmacol Ther 2014; 40:695.
- 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.
- Kurtz RC, Bronzo RL. Does spontaneous bacterial peritonitis occur in malignant ascites? Am J Gastroenterol 1982; 77:146.
- Runyon BA. Spontaneous bacterial peritonitis associated with cardiac ascites. Am J Gastroenterol 1984; 79:796.
- Woolf GM, Runyon BA. Spontaneous Salmonella infection of high-protein noncirrhotic ascites. J Clin Gastroenterol 1990; 12:430.
- Ackerman Z. Ascites in Nephrotic syndrome. Incidence, patients' characteristics, and complications. J Clin Gastroenterol 1996; 22:31.
- Senkerikova R, de Mare-Bredemeijer E, Frankova S, et al. Genetic variation in TNFA predicts protection from severe bacterial infections in patients with end-stage liver disease awaiting liver transplantation. J Hepatol 2014; 60:773.