Spontaneous bacterial peritonitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2], Chetan Lokhande, M.B.B.S [3], Guillermo Rodriguez Nava, M.D. [4], Alejandro Lemor, M.D. [5] Shivani Chaparala M.B.B.S [6]

Overview

Empiric broad-spectrum intravenous antibiotic, preferably with a third generation cephalosporin such as cefotaxime, is warranted for suspected or established spontaneous bacterial peritonitis (SBP) to cover the most common isolates including Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae. Oral ofloxacin may be considered in selected cases. Albumin infusion should be reserved for patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm³ and clinical suspicion of SBP, who also have a serum creatinine >1 mg/dL, blood urea nitrogen >30 mg/dL, or total bilirubin >4 mg/dL. The use of non-selective beta blockers in cirrhotic patients with SBP should be discouraged since it is associated with an increased risk for hemodynamic compromise, prolonged hospitalization, hepatorenal syndrome, and acute kidney injury.

Medical Therapy Adapted from AASLD Practice Guidelines: Management of Adult Patients with Ascites Due to Cirrhosis.

Empiric Therapy
Preferred Regimen
▸ Cefotaxime 2 g IV q8h (or 2 g IV q4h if life-threatening) x 5–10 days
Alternative Regimen
▸ Ofloxacin 400 mg PO bid x 5–10 days† OR ▸ Ciprofloxacin 200 mg IV q12h x 7 days† OR ▸ Ciprofloxacin 200 mg IV q12h x 2 days, then 500 mg PO bid x 5 days†
† Should not be used in a patient who had been receiving a quinolone for prophylaxis.
ESBL–producing Enterobacteriaceae†
Preferred Regimen
▸ Doripenem 500 mg IV q8h (1–hr infusion) OR ▸ Ertapenem 1 g IV q24h OR ▸ Imipenem–Cilastatin 0.5–1 g IV q6–8h OR ▸ Meropenem 1 g IV q8h
Alternative Regimen
▸ Ciprofloxacin 400 mg IV q12h OR ▸ Levofloxacin 750 mg IV q24h OR ▸ Moxifloxacin 400 mg IV q24h
† Check in vitro susceptibility.

• Empiric antibiotic therapy should be administered to patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm³ in a clinical setting compatible with ascitic fluid infection or those who have convincing signs or symptoms of infection (fever, abdominal pain, or unexplained encephalopathy) regardless of the PMN count in the ascitic fluid.

• Bacterascites is defined as an ascitic neutrophil count less than 250/mm³ but with a positive ascitic fluid culture. If the patient exhibits signs of systemic inflammation or infection, the patient should be treated with antibiotics. Otherwise, the patient should undergo a second paracentesis when culture results turns positive. Patients in whom the repeat ascitic neutrophil count is >250/mm³ should be treated for SBP, and the remaining patients (i.e., neutrophils <250/mm³) should be followed up.

• The most common isolates from the ascitic fluid are Escherichia coli, Klebsiella pneumoniae, and Streptococcus pneumoniae.

• Relatively broad-spectrum therapy, preferably with cefotaxime, is warranted until the results of susceptibility testing are available.

• Infection with multiresistant organism including Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus faecium is associated with an increased mortality. Risk factors for multiresistant infections include:

• Nosocomial origin of infection
• Long-term norfloxacin prophylaxis
• Recent infection with multiresistant bacteria
• Recent use of beta-lactams

• Oral ofloxacin may be used alternatively in selected cases such as patients without vomiting, shock, grade II (or higher) hepatic encephalopathy, or serum creatinine greater than 3 mg/dL.

• The optimal duration of therapy remains unclear, although most patients respond to a treatment course of five days. Infection-related mortality, bacteriologic cure, and recurrence of ascitic fluid infection were not significantly different between the 5- and 10-day treatment groups in a randomized trial.

Adjunctive IV Albumin

• In a randomized controlled study involving cirrhotic patients with SBP, the use of IV albumin (1.5 g/kg given within 6 hours of enrollment and repeated as a 1.0 g/kg dose on day 3) as an adjunctive to cefotaxime was shown to decrease in-hospital mortality when compared with use of cefotaxime alone (29% versus 10%).

• In addition, those treated with albumin had a reduction in the development of renal impairment (10% versus 33%).
• Use of IV albumin should be reserved for patients with a:
  • Serum creatinine greater than 1 mg/dL,
  • Blood urea nitrogen greater than 30 mg/dL, or
  • Total bilirubin greater than 4 mg/dL.

Recommendations for the Management of Spontaneous Bacterial Peritonitis (2013 AASLD Practice Guideline)

“

Patients with ascites admitted to the hospital should undergo abdominal paracentesis. Paracentesis should be repeated in patients (whether in the hospital or not) who develop signs or symptoms or laboratory abnormalities suggestive of infection (e.g., abdominal pain or tenderness, fever, encephalopathy, renal failure, acidosis, or peripheral leukocytosis). Patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm3 in a community-acquired setting in the absence of recent beta-lactam antibiotic exposure should receive empiric antibiotic therapy, e.g., an intravenous third-generation cephalosporin, preferably cefotaxime 2 g every 8 hours. Patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm3 in a nosocomial setting and/or in the presence of recent beta-lactam antibiotic exposure should receive empiric antibiotic therapy based on local susceptibility testing of bacteria in patients with cirrhosis. Oral ofloxacin (400 mg twice per day) can be considered a substitute for intravenous cefotaxime in inpatients without prior exposure to quinolones, vomiting, shock, grade II (or higher) hepatic encephalopathy, or serum creatinine greater than 3 mg/dL. Patients with ascitic fluid PMN counts less than 250 cells/mm3 and signs or symptoms of infection (temperature >100ºF or abdominal pain or tenderness) should also receive empiric antibiotic therapy, e.g., intravenous cefotaxime 2 g every 8 hours, while awaiting results of cultures. When the ascitic fluid of a patient with cirrhosis is found to have a PMN count greater than or equal to 250 cells/mm3 and there is high suspicion of secondary peritonitis, it should also be tested for protein, lactic dehydrogenase, glucose, Gram’s stain, carcinoembryonic antigen, and alkaline phosphatase to assist with the distinction of SBP from secondary peritonitis. Computed tomographic scanning should also be performed. Patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm3 in a nosocomial setting and/or in the presence of recent beta-lactam antibiotic exposure and/or culture an atypical organism(s) or have an atypical clinical response to treatment, should undergo a follow-up paracentesis after 48 hours of treatment to assess the response in PMN count and culture. Patients with ascitic fluid PMN counts greater than or equal to 250 cells/mm3 and clinical suspicion of SBP, who also have a serum creatinine >1 mg/dL, blood urea nitrogen >30 mg/dL, or total bilirubin >4 mg/dL should receive 1.5 g albumin per kg body weight within 6 hours of detection and 1.0 g/kg on day 3.

”

Followup Diagnostic Paracentesis

• Follow-up ascitic fluid analysis is usually not necessary following treatment of SBP, unless there is no clinical improvement in the patient’s symptoms, abnormal fluid analysis, suspected infection with multi-drug resistant organisms, or altered clinical course is noted.
• If the ascitic fluid PMN count has not declined by at least 25% after two days of antibiotic therapy, then the antibiotic coverage needs to be broadened to cover resistant organisms and secondary bacterial peritonitis needs to be considered.
• Patients with secondary bacterial peritonitis should undergo surgical intervention of the perforated viscus or drainage of the abscess and should be treated with broad-spectrum antibiotics, such as third-generation cephalosporins, with the addition of an antimicrobial agent that has good anaerobic coverage, such as metronidazole
  • Consider repeat paracentesis after 48hours of therapy
  • Consider changing antibiotics if ascitic fluid PMN has not dropped by 25% after 48 hours and/or patient is not responding clinically.