Spontaneous Bacterial Peritonitis Prophylaxis
Direct Answer
Norfloxacin 400 mg orally once daily is the standard prophylactic antibiotic for patients at high risk of SBP, including those with prior SBP (secondary prophylaxis), acute gastrointestinal hemorrhage, or low ascitic fluid protein with advanced liver disease (primary prophylaxis). 1, 2
Three High-Risk Populations Requiring Prophylaxis
1. Secondary Prophylaxis (Prior SBP Episode)
All patients who have recovered from an episode of SBP require indefinite antibiotic prophylaxis. 1, 2
- Norfloxacin 400 mg orally once daily reduces SBP recurrence from 68% to 20% at one year 1, 2, 3
- Ciprofloxacin 500 mg orally once daily is an acceptable alternative, particularly in the UK where norfloxacin may be unavailable 1, 2, 3
- Prophylaxis should continue indefinitely until liver transplantation or resolution of ascites 4
- All patients with prior SBP should be evaluated for liver transplantation due to poor long-term survival 4, 5
Common Pitfall: Only one-third of patients who survive SBP receive appropriate long-term outpatient prophylaxis after discharge—this represents a critical gap in care 6
2. Acute Gastrointestinal Hemorrhage
Every cirrhotic patient with acute GI bleeding requires antibiotic prophylaxis regardless of ascites presence. 1, 4
- Bacterial infections occur in 25-65% of cirrhotic patients with GI bleeding 1
- Infection increases rebleeding rates and mortality 1
Antibiotic regimen based on disease severity:
- Advanced cirrhosis (Child-Pugh C): IV ceftriaxone 1g daily for 7 days 4, 3
- Less severe disease: Norfloxacin 400 mg orally twice daily for 7 days 1, 3
- Continue until bleeding resolves and vasoactive drugs are discontinued 4
Critical Pitfall: GI hemorrhage is the most frequently overlooked indication for SBP prophylaxis, accounting for 44% of preventable SBP cases 6
3. Primary Prophylaxis (No Prior SBP)
Primary prophylaxis is controversial but recommended for highly selected patients with multiple risk factors. 1, 4
Indications for primary prophylaxis (must meet criteria):
- Ascitic fluid protein <15 g/L (1.5 g/dL) PLUS at least one of the following: 1, 4
- Child-Pugh score ≥9 with serum bilirubin ≥3 mg/dL
- Impaired renal function (creatinine ≥1.2 mg/dL or BUN ≥25 mg/dL)
- Hyponatremia (serum sodium ≤130 mEq/L)
Recommended regimen:
- Norfloxacin 400 mg orally once daily reduces SBP development from 61% to 7% 4
- Ciprofloxacin 500 mg orally once daily is an alternative 1, 3
Important Controversy: The 2016 NORFLOCIR trial (large placebo-controlled RCT) showed norfloxacin did NOT reduce 6-month mortality in primary prophylaxis, raising questions about broad application 1. Therefore, restrict primary prophylaxis to the highest-risk patients meeting multiple criteria above rather than using ascitic protein <15 g/L alone.
Emerging Resistance Concerns
Long-term fluoroquinolone prophylaxis has significant drawbacks that must be considered: 1, 4, 3
- Increasing multidrug-resistant organisms (MDRO), with nosocomial SBP now showing 35% MDRO rate 2
- Shift toward gram-positive infections (Staphylococcus, Enterococcus, MRSA) 3, 5, 7
- Quinolone-resistant bacteria are increasingly common 1
- Consider local resistance patterns when selecting prophylactic antibiotics 2, 4
Rifaximin: Not Currently Recommended
Despite promising research, rifaximin is NOT endorsed by current guidelines for SBP prophylaxis. 4
- EASL, AASLD, and BSG guidelines (2018-2021) do not recommend rifaximin as an alternative to norfloxacin 4
- A 2019 network meta-analysis suggested rifaximin may be superior to norfloxacin 8, but this has not been incorporated into major guidelines
- For patients already on rifaximin for hepatic encephalopathy who develop SBP, ADD norfloxacin for secondary prophylaxis—do not rely on rifaximin monotherapy 4
Additional Risk Reduction Strategies
Beyond antibiotics, consider these evidence-based interventions: 4, 5
- Strongly consider discontinuing proton pump inhibitors (PPIs) in patients on SBP prophylaxis, as PPIs increase SBP risk 4
- Discontinue non-selective beta-blockers in patients with end-stage liver disease and refractory ascites (standard care) 5
- Monitor renal function regularly in patients on prophylactic antibiotics 4
Treatment of Active SBP (When Prophylaxis Fails)
If SBP develops despite prophylaxis, immediate empirical treatment is required: 2
- Community-acquired SBP: Cefotaxime 2g IV every 8-12 hours or ceftriaxone 1-2g IV every 12-24 hours 2
- Nosocomial/healthcare-associated SBP: Meropenem 1g IV every 8 hours plus daptomycin 6 mg/kg/day (due to high MDRO prevalence) 2
- Mandatory adjunctive therapy: IV albumin 1.5 g/kg at diagnosis, then 1 g/kg on day 3—reduces hepatorenal syndrome from 30% to 10% and mortality from 29% to 10% 1, 2, 4
- Repeat paracentesis at 48 hours to confirm neutrophil count decrease >25% from baseline 2
Key Clinical Pitfalls to Avoid
- 62% of SBP cases are potentially preventable by adhering to prophylaxis guidelines 6
- GI hemorrhage is the most commonly missed indication (44% of preventable cases) 6
- Failure to prescribe long-term prophylaxis after SBP discharge (only 33% receive it) 6
- Using quinolone prophylaxis in patients with known quinolone-resistant colonization 4
- Delaying empirical antibiotics while waiting for culture results 2