Spontaneous Bacterial Peritonitis James Han May 2018

Objectives Learn to diagnose spontaneous bacterial peritonitis (SBP) Learn how to treat SBP Know the indications for the primary prophylaxis of SBP and the treatment regimen

Diagnosis Diagnosed by performing paracentesis of ascites fluid Do the paracentesis BEFORE antibiotics as ascites fluid sterilizes quickly (86% chance of negative culture 6 hours after antibiotic use [3]) Early recognition of need for paracentesis is key! Each hour of delay in paracentesis leads to a 3.3% increase in mortality! (1) Send ascites fluid for Cell count Gram stain Culture In addition to ascites cell count of ≥ 250 PMNs AND a positive culture, secondary causes of peritonitis should be excluded. Utility of an algorithm in differentiating spontaneous from secondary bacterial peritonitis.AUAkriviadis EA, Runyon BA SOGastroenterology. 1990;98(1):127. 

Diagnosis Diagnostic criteria ascites PMN cell count of ≥ 250 PMNs/mm3 positive ascites culture secondary causes of bacterial peritonitis ruled out ALL PATIENTS WITH PMN >250 SHOULD BE STARTED ON ANTIBIOTICS EMPIRICALLY WHILE WAITING FOR CULTURES How to calculate the number of PMNs in ascitic fluid: Ascitic fluid cell count multiplied by the percentage of PMNs Example: Ascitic fluid cell count is 1,000 and there are 30% PMNs -> The number of PMNs is 1,000 x 0.3 = 300 Causes of secondary peritonitis include traumatic ascites, bowel perforation, iatrogenic causes. Suspect secondary causes of peritonitis when ascites Total protein >1g/dl Glucose <50mg/dl LDH> upper limit of normal for serum The ascites culture for SBP is usually polymicrobial. Microbiology: 70% GNR (E. coli, Klebsiella), 30% GPC (enterococcus, S. pneumo), nosocomial (fungi, pseudomonas) There are different types of ascites which can be characterized by the ascites cell count and culture. There is culture-negative neutrocytic ascites (CNNA) with ≥ 250 PMNs but a negative culture. Clinically and prognostically like SBP; need to look for TB, carcinomatosis, pancreatitis. There is non-neutrocytic bacterascites (NNBA) with <250 PMNs, but a positive culture (usually one organism). This acts like SBP (may be early SBP) when there are symptoms; without symptoms has better prognosis, but need to re-tap. Correction needed if traumatic paracentesis occurs as it can lead to erroneous PMN count True PMN = absolute PMN – (absolute RBC/250)

Treatment Inpatient treatment 3rd generation cephalosporin – typically ceftriaxone at 2g IV daily x 5 days Stop non-selective beta blockers (typically propranolol or carvedilol) – associated with worse outcomes [4] Outpatient treatment – for uncomplicated SBP only. Ciprofloxacin 500mg BID x 5 days Avoid if patient has been on oral FQNs for prophylaxis Treatment is Cefotaxime 2 gm IV q8 hours for 5 days. Oral fluoroquinolone treatment may be indicated in ambulatory patients with stable hepatic and kidney function, and no evidence of encephalopathy. Use of concurrent IV albumin at 1.5 g/kg on admission and 1 g/kg on day 3 has been shown to decrease in-hospital mortality by 20% in patients with serum creatinine values of 1.5 mg/dL or greater. Patients with advanced liver disease, including those with a serum total bilirubin of 4 or greater, also benefit from IV albumin to prevent kidney failure associated with SBP. Uncomplicated SBP = stable renal and hepatic function and no encephalopathy OR asymptomatic Nonselectiveβblockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis.AUMandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Kruzik M, Hagmann M, Blacky A, Ferlitsch A, Sieghart W, Trauner M, Peck-Radosavljevic M, Reiberger T SOGastroenterology. 2014;146(7):1680. Epub 2014 Mar 12. 

Treatment The addition of IV albumin 1.5 g/kg at the time of diagnosis and 1 g/kg on day three may increase survival and reduce the rate of renal impairment if the patient has the following Creatinine >1 mg/dL BUN >30 mg/dL Total bilirubin >4 mg/DL If patient is not improving, consider repeat paracentesis at 48 hours If secondary peritonitis is suspected or polymicrobial peritonitis is present Add metronidazole

Prophylaxis Benefits of prophylaxis: Indication Regimen 1 Regimen 2 Ascitic fluid total protein < 1g/dL Ciprofloxacin 500mg daily Bactrim DS daily Prior History of SBP Gastrointestinal Hemorrhage Ceftriaxone 1g IV, then ciprofloxacin 500mg BID x 5 days Ciprofloxacin 500mg BID x 5 days Benefits of prophylaxis: Improves 1 year survival probability Reduces 1 year probability of SBP Minimize use of PPIs (associated with increased risk of SBP) [5] Regimen 1 for GI hemorrhage prophylaxis is for Childs Pugh class B, regimen 2 is for Childs Pugh class A Benefits of ppx: Improved 1 year survival probability from 48% to 60% Reduces 1 year probability of SBP from 61% to 7% Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of SBP delays hepatorenal syndrome and imporves survival in cirrhosis. Gastroenterology 2007; 133:818-24. 5) Increased rate of spontaneous bacterial peritonitis among cirrhotic patients receiving pharmacologic acid suppression.AUGoel GA, Deshpande A, Lopez R, Hall GS, van Duin D, Carey WD SOClin Gastroenterol Hepatol. 2012;10(4):422. Epub 2011 Dec 7.

Case Study A 45 year old man is admitted to the hospital for a two day history of fever and abdominal pain. His medical history is notable for cirrhosis due to chronic hepatitis C, esophageal varices, ascites, and minimal hepatic encephalopathy. He has ascites on exam. Labs: WBC 3.5, Hgb 10, Plt 70. Cr 1.8. Total bilirubin 4. ALT 30, AST 40. Diagnostic paracentesis discloses a cell count of 2,000/microliter with 20% neutrophils, a total protein level 0.8 g/dL, and an albumin of 0.6 g/dL. Ascitic fluid culture is positive. What is his diagnosis? What is the most appropriate treatment? Should he be on prophylaxis and if so, what kind? Diagnosis: He has spontaneous bacterial peritonitis. The diagnosis is made in the setting of a positive ascitic fluid bacteria culture and elevated ascitic fluid absolute PMN cell count (>=250/microliter) without e/o secondary causes of peritonitis. Treatment: cefotaxime 2 gm IV q8 hours for 5 days plus albumin. The use of cefotaxime plus albumin at 1.5 g/kg on admission and 1g/kg on day 3 has been shown to decrease in-hospital mortality by 20% of patient with serum Cr >= 1.5, as in this patient. Remember, patients with advanced liver disease, including those with total bilirubin of >=4, as in this patient, also benefit from IV albumin to prevent kidney failure.

Summary Spontaneous bacterial peritonitis (SBP) is diagnosed by an ascites fluid cell count of ≥ 250 PMNs and a positive ascites fluid culture. Treatment of SBP is IV ceftriaxone 2g daily x 5 days with IV albumin 1.5 g/kg on day one and 1 g/kg on day 3. The concomitant use of albumin with antibiotic therapy is associated with a survival benefit compared with antibiotic therapy alone. Primary prophylaxis of SBP is indicated if the patient has an ascitic fluid total protein (AFTP) < 1, has a history of SBP, or has gastrointestinal bleeding, typically with Bactrim DS daily or ciprofloxacin 500mg daily.