What is the recommended prophylaxis regimen for a patient with cirrhosis and ascites at high risk of developing Spontaneous Bacterial Peritonitis (SBP)?

Prophylaxis for Spontaneous Bacterial Peritonitis in Cirrhosis

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 specific indications based on risk stratification. 1

Secondary Prophylaxis (After Prior SBP Episode)

All patients who have survived an episode of SBP must receive continuous prophylaxis indefinitely until liver transplantation or resolution of ascites. 1

• Norfloxacin 400 mg once daily reduces SBP recurrence from approximately 70% to 20% at one year and dramatically improves 3-month survival from 62% to 94%. 2, 1
• This represents a Level A1 recommendation with the strongest evidence base from multiple randomized controlled trials. 2
• Alternative regimens include ciprofloxacin 500 mg once daily or co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim) once daily. 1, 3
• All patients with prior SBP should be evaluated for liver transplantation given their poor long-term prognosis. 3

Primary Prophylaxis (High-Risk Patients Without Prior SBP)

Primary prophylaxis is indicated for patients meeting both of the following criteria: 2, 1

• Ascitic fluid protein <15 g/L (or <1.5 g/dL) AND
• Advanced liver disease, defined as:
  • 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 sodium ≤130 mEq/L) 2

Norfloxacin 400 mg once daily reduces the 1-year probability of developing SBP from 61% to 7% in these high-risk patients and significantly improves survival. 2, 1

The evidence supporting primary prophylaxis comes from multiple randomized controlled trials, with the landmark Fernández 2007 study demonstrating the most dramatic survival benefit (3-month survival 94% vs 62%, p=0.003). 2

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 and significantly increase mortality. 1, 4

The regimen depends on disease severity: 2, 1

• Advanced liver disease (Child-Pugh B/C or at least 2 of: ascites, severe malnutrition, encephalopathy, bilirubin >3 mg/dL):

  • IV ceftriaxone 1 g daily for 7 days (superior to norfloxacin in preventing infections) 2

• Less severe liver disease:

  • Norfloxacin 400 mg orally twice daily for 7 days 2, 1
  • Alternative: oral quinolone if norfloxacin unavailable 2

A recent comparative study demonstrated ceftriaxone's superiority over norfloxacin in patients with advanced cirrhosis and GI bleeding, making it the prophylactic antibiotic of choice in this high-risk setting. 2

Alternative Antibiotic Options

When norfloxacin is unavailable or contraindicated: 1, 3, 5

• Ciprofloxacin 500 mg once daily (acceptable alternative with similar efficacy)
• Co-trimoxazole 800/160 mg once daily (similar efficacy but may have increased adverse events)
• Rifaximin (more effective than norfloxacin in secondary prophylaxis with decreased adverse events in one study) 5
• Weekly ciprofloxacin was non-inferior to daily norfloxacin in one trial, though this is not standard practice 5

Critical Monitoring and Pitfalls

Long-term quinolone prophylaxis increases the risk of gram-positive infections and multidrug-resistant organisms, representing a major concern with prolonged use. 1, 3, 4

Key monitoring requirements: 1, 3

• Regular renal function monitoring in all patients on prophylactic antibiotics
• Monitor for tendon pain or inflammation (fluoroquinolone side effect) and discontinue immediately if it occurs
• Perform diagnostic paracentesis if clinical deterioration occurs despite prophylaxis
• Consider local bacterial resistance patterns when selecting antibiotics, as resistance to quinolones is increasing 3, 4

Restrict proton pump inhibitor (PPI) use in cirrhotic patients, as PPIs may independently increase SBP risk. 1, 3

Common Clinical Errors

A retrospective analysis found that 62% of SBP cases were potentially preventable through adherence to prophylaxis guidelines. 6 The most frequently overlooked indications were: 6

• GI hemorrhage (44% of missed cases)
• Serum bilirubin ≥2.5 mg/dL (33% of missed cases)
• Prior SBP (11% of missed cases)
• Ascitic fluid protein ≤1 g/dL (11% of missed cases)

Additionally, only one-third of patients who survived SBP received appropriate long-term outpatient prophylaxis after discharge, representing a critical gap in care. 6