What is the recommended prophylaxis regimen for patients at high risk of Spontaneous Bacterial Peritonitis (SBP)?

Spontaneous Bacterial Peritonitis Prophylaxis

Antibiotic prophylaxis for SBP must be restricted to three specific high-risk populations: patients with prior SBP (secondary prophylaxis), patients with acute gastrointestinal hemorrhage, and patients with low ascitic fluid protein (<1.5 g/dL) plus advanced liver disease (primary prophylaxis). 1

High-Risk Populations Requiring Prophylaxis

Secondary Prophylaxis (Prior SBP)

Patients who have recovered from an episode of SBP require indefinite antibiotic prophylaxis until liver transplantation or resolution of ascites. 1

• Norfloxacin 400 mg orally once daily is the first-line agent, reducing recurrence from 68% to 20% at one year 1, 2
• Ciprofloxacin 500 mg orally once daily is an acceptable alternative, particularly since norfloxacin was withdrawn from the US market in 2014 1
• Rifaximin showed promising results in one single-center trial (4% vs 14% recurrence at 6 months compared to norfloxacin), but current EASL and AASLD guidelines do not endorse rifaximin for SBP prophylaxis due to insufficient evidence 1, 2
• All patients with prior SBP should be evaluated for liver transplantation given poor long-term survival 1, 3

Acute Gastrointestinal Hemorrhage

All cirrhotic patients with acute GI bleeding require short-term antibiotic prophylaxis (5-7 days) regardless of ascites presence, as bacterial infections occur in 25-65% of these patients and significantly increase rebleeding rates and mortality. 1

• For patients with advanced cirrhosis or severe hemorrhage: IV ceftriaxone 1g daily for 7 days 1, 3
• For less severe disease: Norfloxacin 400 mg orally twice daily for 7 days 1, 3
• Antibiotic prophylaxis reduces both severe infections and mortality in this population 1

Primary Prophylaxis (High-Risk Patients Without Prior SBP)

Primary prophylaxis should be reserved for patients with ascitic fluid protein <1.5 g/dL (or <10-15 g/L) PLUS at least one of the following: advanced liver failure (Child-Pugh ≥9 with bilirubin ≥3 mg/dL), impaired renal function (creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL, or serum sodium ≤130 mEq/L). 1, 2

• Norfloxacin 400 mg orally once daily reduces SBP development from 61% to 7% and improves 3-month survival 2, 3
• This prophylaxis should continue until liver transplantation or resolution of ascites 2
• Rifaximin has no established role in primary prophylaxis according to current EASL guidelines 2

Important Clinical Considerations and Pitfalls

Antibiotic Resistance Concerns

Long-term fluoroquinolone prophylaxis increases the risk of gram-positive infections (including MRSA) and multidrug-resistant organisms. 1, 3

• The epidemiology of SBP has shifted toward more gram-positive cocci and quinolone-resistant bacteria 1, 3
• Quinolone prophylaxis is less effective in patients already colonized with multidrug-resistant organisms 1
• Consider local bacterial resistance patterns when selecting prophylactic antibiotics 3

Common Prophylaxis Errors

GI hemorrhage is the most frequently overlooked indication for SBP prophylaxis, accounting for 44% of preventable SBP cases in one study. 4

• Up to 62% of SBP cases could be prevented by adhering to established guidelines 4
• Only one-third of patients who survive SBP receive appropriate long-term outpatient prophylaxis after discharge 4

Additional Risk Modification

Consider restricting proton pump inhibitor use in patients on SBP prophylaxis, as PPIs may increase SBP risk. 2

• Non-selective beta-blockers should be temporarily held in patients who develop hypotension (MAP <65 mmHg) or acute kidney injury 1
• Regular monitoring of renal function is recommended in patients on prophylactic antibiotics 2

Special Situations

For patients already on rifaximin for hepatic encephalopathy who develop SBP, add norfloxacin for secondary prophylaxis rather than relying on rifaximin monotherapy, as there is no evidence supporting rifaximin alone for this indication. 2