Review Article

Spontaneous Bacterial Peritonitis – Bacteriology, Diagnosis, Treatment, Risk Factors and Prevention

J. B. Dever; M. Y. Sheikh

Disclosures

Aliment Pharmacol Ther. 2015;41(11):1116-1131. 

In This Article

Risk Factors

Biochemical Risk Factors

Well-established risk factors for developing an initial episode of SBP are low ascitic fluid protein level (<1 g/dL), elevated serum bilirubin level and advanced cirrhosis.[71,72] The probability of developing an initial episode of SBP was substantially higher (24%) in patients with a low ascitic protein level (<1 g/dL) compared to higher levels (4%) at 3 year follow-up of 127 patients.[73] Low levels of 25-hydroxy vitamin D have been associated with mortality in patients with cirrhosis[74] and development of SBP independent of Child–Pugh score.[75]

Risk factors for recurrence, based on univariate analysis, are serum bilirubin (>4 mg/dL), prothrombin (≤45%) and low ascitic fluid protein concentration (<1 g/dL).[76] Likewise, after evaluating 86 patients who survived a first episode of SBP, a serum albumin level less than 2.85 g/dL at hospital discharge was strongly associated with SBP recurrence.[77]

Clinical Risk Factors

Variceal haemorrhage predisposes to SBP,[78,79] and randomised trials have shown reduction in infection and mortality when antibiotics are administered upon admission,[80,81] now a standard of care in all patients with cirrhosis and gastrointestinal bleeding whether or not ascites is present.[82]

Genetic Risk Factors

The Toll-like receptor 2 (TLR2) proteins are expressed in macrophages and are essential for recognition of microbial components and host cell defence. One hundred and fifty patients with cirrhosis and ascites were genotyped for TLR2, and those with specific TLR2 variants had a significant risk of developing SBP (38.5% vs. 15.3%, P = 0.002).[83] Similarly, variants of the NOD2 (nucleotide-binding oligomerisation domain containing 2) gene were initially found to impair mucosal integrity in Crohn disease in earlier studies and have also shown to increase the risk of SBP [P = 0.008, odds ratio (OR) = 3.06] and early death (P = 0.007) compared to wildtype genotypes in patients with cirrhosis and ascites.[84] Farnesoid X is a cellular protein and nuclear receptor and its polymorphisms have also been associated with risk of SBP in cirrhotic patients with ascites.[85]

Pharmacological Risk Factors

Acid Suppressive Therapy. Proton pump inhibitors (PPI) increase gastric pH, impair natural host defence against ingested bacteria and predispose to an altered intestinal milieu. PPIs have been associated with pneumonia and implicated in other infections such as SBP. In fact, PPI therapy has been associated with and identified as an independent risk factor for SBP in patients with advanced cirrhosis in retrospective series[86,87] as well as prospective series, and its use should be curtailed or at least re-examined in this population as 50% of patients who develop SBP have no documented indication for PPI therapy.[88] In a meta-analysis, PPI therapy was found to increase the risk of SBP by three-fold in hospitalised patients with cirrhosis compared to those not receiving acid suppressive medication.[89] In another meta-analysis including four studies with 772 patients, there was a significant association between PPI use and SBP (OR 2.77, 95% CI 1.82–4.23).[90] Moreover, in a large multi-centre prospective study examining 188 hospitalised patients with cirrhosis and infections, PPI therapy imposed the highest risk for re-infection including SBP (OR 2.94, 95% CI, 1.39–6.20) within 6 months.[91] Cause and effect of PPI-related SBP has not been proven. However, PPI therapy and its association with other infections is widely familiar and applying these concepts is at the discretion of the clinician on a case-by-case basis until there is surmounting evidence to restrict its use in patients with ascites.

Beta-adrenergic Antagonist Therapy. Beta-adrenergic antagonists namely nonselective beta-blocker (NSBB) therapy was found to be protective for SBP as reported in a meta-analysis examining three retrospective and three randomised controlled trials, which demonstrated a statistically significant difference (12.1%, P < 0.001) in favour of propranolol for SBP prevention in patients with predominantly Child class A and B cirrhosis.[92] However, evidence and expert opinion herald caution with NSBB use in patients with end-stage liver disease and discontinuation of such therapy in the setting of refractory ascites due to poor cardiac compensatory reserve in these patients.[93] Survival was significantly decreased in patients with cirrhosis and refractory ascites who were receiving NSBBs as opposed to patients not receiving NSBBs who lived nearly 2 years longer.[94] NSBB therapy also reduced transplant-free survival in patients with cirrhosis after a first episode of SBP and conferred greater risk for complications requiring hospitalisation such as haemodynamic instability and renal insufficiency.[95]

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