What is the recommended prophylaxis for Spontaneous Bacterial Peritonitis (SBP) in patients with cirrhosis and ascites?

Prophylaxis for Spontaneous Bacterial Peritonitis (SBP)

Norfloxacin 400 mg once daily is the first-line prophylactic antibiotic for both primary and secondary prevention of SBP in cirrhotic patients with ascites, with ciprofloxacin 500 mg daily or co-trimoxazole as acceptable alternatives. 1, 2, 3

Secondary Prophylaxis (After Previous SBP Episode)

All patients who have recovered from an episode of SBP must receive continuous prophylaxis indefinitely until liver transplantation or resolution of ascites. 1, 2, 3

• Norfloxacin 400 mg once daily is the standard regimen, reducing recurrence from approximately 70% to 20% at one year 1, 2
• This prophylaxis improves 3-month survival from 62% to 94% 1
• Alternative options include:
  • Ciprofloxacin 500 mg once daily 1, 3
  • Co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim) once daily 1
• Without prophylaxis, 1-year mortality after SBP is 50-70%, making continuous prevention critical 1
• All patients with prior SBP should be evaluated for liver transplantation due to poor long-term survival (30-50% at 1 year, 25-30% at 2 years) 2, 3

Primary Prophylaxis (No Prior SBP)

Primary prophylaxis is indicated for high-risk patients but remains more controversial than secondary prophylaxis. 4

Indications for Primary Prophylaxis:

The European Association for the Study of the Liver recommends norfloxacin 400 mg daily for patients meeting ALL of the following criteria: 4, 1

• Ascitic fluid protein <15 g/L (1.5 g/dL) AND

• Advanced liver disease defined by:

  • Child-Pugh score ≥9 points with serum bilirubin ≥3 mg/dL, OR
  • Impaired renal function (creatinine ≥1.2 mg/dL, BUN ≥25 mg/dL, or serum sodium ≤130 mEq/L) 4, 1, 2

• In these high-risk patients, norfloxacin reduces the 1-year probability of developing SBP from 61% to 7% 2, 3

• The American Association for the Study of Liver Diseases also supports this approach for patients with ascitic fluid protein <1.5 g/dL plus impaired renal function or liver failure 4

Important Caveat:

The NORFLOCIR trial (a large placebo-controlled RCT) showed that norfloxacin did not reduce 6-month mortality in patients with advanced cirrhosis (>95% had no prior SBP), creating uncertainty about broad primary prophylaxis recommendations 4

Prophylaxis During Acute Gastrointestinal Bleeding

All cirrhotic patients with acute GI bleeding require antibiotic prophylaxis, as bacterial infections occur in 25-65% of these patients. 2, 3

Regimen Selection:

• Advanced liver disease (Child-Pugh B/C): IV ceftriaxone 1g daily for 7 days 2, 3
• Less severe disease: Norfloxacin 400 mg orally twice daily for 7 days 2, 3

Antibiotic Selection and Alternatives

First-Line Agent:

• Norfloxacin 400 mg once daily is the most extensively studied agent with the strongest evidence base 1, 3, 5

Alternative Agents:

• Ciprofloxacin 500 mg once daily is commonly used in the UK and is an acceptable alternative 1, 3
• Co-trimoxazole (800/160 mg) once daily has similar efficacy to norfloxacin but may have increased adverse events 1, 5
• Rifaximin was more effective than norfloxacin in one study for secondary prophylaxis with decreased adverse events and mortality, though less extensively studied 5
• Avoid weekly ciprofloxacin regimens as they may lead to higher rates of quinolone-resistant organisms 1

Critical Monitoring and Pitfalls

Resistance Concerns:

• Long-term quinolone prophylaxis increases risk of gram-positive infections (including MRSA) and multidrug-resistant organisms 1, 2, 3
• Consider local bacterial resistance patterns when selecting antibiotics 1, 2, 3
• If a patient on quinolone prophylaxis develops SBP, avoid fluoroquinolones for treatment and use third-generation cephalosporins instead 2

Monitoring Requirements:

• Regular renal function monitoring is essential in patients on prophylactic antibiotics 1, 2
• Monitor for tendon pain or inflammation (fluoroquinolone side effect), particularly in patients with renal impairment, and discontinue at first sign 1, 2
• Perform diagnostic paracentesis if clinical deterioration occurs despite prophylaxis 2

Additional Considerations:

• Restrict proton pump inhibitor (PPI) use in cirrhotic patients, as PPIs may increase SBP risk 1, 2
• If ascitic fluid neutrophil count fails to decrease to <25% of pretreatment value at 48 hours during treatment, suspect antibiotic resistance or secondary peritonitis 4