Antibiotic Prophylaxis for Spontaneous Bacterial Peritonitis
Cirrhotic patients with ascites who have survived an episode of SBP should receive indefinite daily norfloxacin 400 mg (or ciprofloxacin 500 mg) until liver transplantation or death, as this reduces recurrence from 68% to 20%. 1
Secondary Prophylaxis (After Prior SBP Episode)
The strongest indication for long-term antibiotic prophylaxis is a history of prior SBP. 1
- Norfloxacin 400 mg orally once daily is the most extensively studied and recommended first-line agent 1, 2
- Ciprofloxacin 500 mg orally once daily is an acceptable alternative, commonly used in the UK 1, 2
- Trimethoprim/sulfamethoxazole (800 mg/160 mg daily) is a third option with less robust evidence 1, 2
Duration: Prophylaxis must continue indefinitely until liver transplantation or death 1, 2. The 1-year recurrence rate without prophylaxis exceeds 70%, and 1-year survival after SBP is only 30-50% 1. No randomized trials support discontinuation at any point 2.
Critical action: All patients who survive SBP should be evaluated for liver transplantation 1, 2.
Primary Prophylaxis (No Prior SBP)
High-Risk Patients with Low Ascitic Fluid Protein
Norfloxacin 400 mg daily (or trimethoprim/sulfamethoxazole) is justified when ascitic fluid protein is <1.5 g/dL AND at least one of the following is present: 1
- Serum creatinine ≥1 mg/dL
- Blood urea nitrogen >25 mg/dL
- Serum sodium <130 mEq/L
- Child-Pugh score >9 with bilirubin >3 mg/dL
This recommendation carries Class I, Level B evidence 1. One trial demonstrated that continuous norfloxacin reduced SBP from 61% to 7% and improved 3-month survival from 62% to 94% in this population 1.
Gastrointestinal Hemorrhage
Every cirrhotic patient with GI bleeding requires short-term antibiotic prophylaxis. 1, 2
- For advanced liver disease (Child-Pugh C, bilirubin >3 mg/dL): Intravenous ceftriaxone 1 g daily for 7 days is preferred 1, 2, 3
- For less severe disease: Norfloxacin 400 mg orally twice daily for 7 days is an alternative 1, 2
This carries Class I, Level A evidence 1. Meta-analysis of 534 patients showed a 32% reduction in infection and 9% increase in survival 1. Ceftriaxone is specifically preferred over quinolones in this setting due to superior coverage against quinolone-resistant organisms 2, 3.
Duration: Continue until hemorrhage is controlled and vasoactive drugs are discontinued, typically 7 days 2, 3.
Resistance Concerns and Treatment Failure
Long-term quinolone prophylaxis selects for resistant organisms, particularly gram-positive bacteria including MRSA. 1, 2, 4
- One center reported a shift from 67% gram-negative to 79% gram-positive infections in patients on long-term quinolone prophylaxis 1
- When SBP develops despite quinolone prophylaxis, empiric treatment must use third-generation cephalosporins (cefotaxime or ceftriaxone), not quinolones 2, 5
- Quinolone-resistant bacteria remain sensitive to cefotaxime in most cases 1
Despite resistance concerns, the mortality benefit of secondary prophylaxis outweighs resistance risks in patients with prior SBP. 3
Common Pitfalls to Avoid
GI hemorrhage is the most frequently overlooked indication for prophylaxis. 6 A retrospective study found that 62% of SBP cases were "preventable" through adherence to guidelines, with GI hemorrhage accounting for 44% of missed opportunities 6.
Do not use ceftriaxone for long-term secondary prophylaxis. 3 Ceftriaxone is reserved for short-term prophylaxis during acute GI bleeding; oral quinolones are the standard for indefinite secondary prophylaxis 2, 3.
Discontinue proton-pump inhibitors when feasible, as they may increase SBP risk 2.
Maintain high clinical suspicion for breakthrough infection despite prophylaxis; perform diagnostic paracentesis immediately when fever, abdominal pain, encephalopathy, or renal dysfunction develop 2.