What medication is used for prophylaxis of Spontaneous Bacterial Peritonitis (SBP)?

Prophylaxis of Spontaneous Bacterial Peritonitis

Norfloxacin 400 mg once daily is the first-line medication for prophylaxis of spontaneous bacterial peritonitis in patients with cirrhosis and ascites. 1, 2

Secondary Prophylaxis (After Prior SBP Episode)

Patients who have survived an episode of SBP require indefinite antibiotic prophylaxis until liver transplantation or death. 1, 2

• Norfloxacin 400 mg daily is the most extensively studied and recommended regimen, reducing SBP recurrence from 68% to 20% at one year 1, 2
• Ciprofloxacin 500 mg once daily is an acceptable alternative, particularly when norfloxacin is unavailable 2, 3
• Weekly ciprofloxacin (750 mg once weekly) has been shown to be non-inferior to daily norfloxacin with similar efficacy and tolerability 4, 5
• All patients recovering from SBP should be evaluated for liver transplantation given the 1-year survival of only 30-50% 1, 3

Primary Prophylaxis (High-Risk Patients Without Prior SBP)

Primary prophylaxis is indicated for patients with ascitic fluid protein <1.5 g/dL (or <15 g/L) combined with advanced liver disease. 1, 2

• Norfloxacin 400 mg daily reduces SBP occurrence from 61% to 7% in high-risk patients 1, 6
• Advanced liver disease criteria include: Child-Pugh score ≥9 with bilirubin ≥3 mg/dL, or impaired renal function (creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL, or serum sodium ≤130 mEq/L) 1, 2
• Continue prophylaxis indefinitely until liver transplantation or resolution of ascites 6, 3

Prophylaxis During Gastrointestinal Bleeding

All cirrhotic patients with acute gastrointestinal bleeding require antibiotic prophylaxis regardless of ascites presence, as bacterial infections occur in 25-65% of these patients. 1, 3

• For advanced cirrhosis (Child-Pugh C, ascites, severe malnutrition, encephalopathy, or bilirubin >3 mg/dL): IV ceftriaxone 1 g daily for 7 days is superior to norfloxacin 1, 2
• For less severe liver disease: Norfloxacin 400 mg twice daily orally for 7 days is an acceptable alternative 1, 3

Alternative Prophylactic Agents

• Trimethoprim-sulfamethoxazole (800 mg/160 mg daily) has similar efficacy to norfloxacin but higher adverse event rates 2, 5
• Rifaximin shows promise in research studies with lower SBP recurrence than norfloxacin (4% vs 14% at 6 months), but is not currently recommended by major guidelines for SBP prophylaxis 6, 5

Critical Caveats and Pitfalls

Increasing bacterial resistance is a major concern with long-term quinolone prophylaxis. 1, 2

• Long-term norfloxacin use increases infections from quinolone-resistant Gram-negative bacteria and Gram-positive organisms including MRSA 1, 3
• Restrict prophylactic antibiotics only to highest-risk patients to minimize resistance development 1, 2
• For patients developing infection with quinolone-resistant bacteria while on prophylaxis, consider switching antibiotics based on susceptibility testing, though formal evidence is lacking 2, 6
• Do not use quinolones for empirical treatment of active SBP in patients already on quinolone prophylaxis - use third-generation cephalosporins instead 1, 2
• Consider limiting proton pump inhibitor use in patients on SBP prophylaxis as PPIs may increase SBP risk 6

Duration of Prophylaxis

Prophylaxis should continue indefinitely until liver transplantation or death. 2, 6

• The 1-year recurrence rate without prophylaxis is approximately 70% 6, 3
• While guidelines note uncertainty about discontinuation in patients with significant liver disease improvement, no specific criteria exist for stopping prophylaxis 2, 6
• Monitor renal function regularly in patients on long-term prophylactic antibiotics 6