What is the recommended primary prophylaxis for Spontaneous Bacterial Peritonitis (SBP)?

Primary Prophylaxis for Spontaneous Bacterial Peritonitis

Primary prophylaxis with norfloxacin 400 mg once daily should be given to cirrhotic patients with ascitic fluid protein <15 g/L who also have advanced liver disease (Child-Pugh ≥9 with bilirubin ≥3 mg/dL) or impaired renal function (creatinine ≥1.2 mg/dL, BUN >25 mg/dL, or sodium ≤130 mEq/L). 1, 2, 3

Patient Selection Criteria

Primary prophylaxis is indicated for high-risk patients who meet both of the following criteria:

• Ascitic fluid protein <15 g/L (some guidelines use <10 g/L as the threshold) 1

PLUS at least one of the following:

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

Important caveat: For patients with low ascitic protein but only moderate liver disease (Child-Pugh 8-9 without the additional criteria above), there is no clear consensus on primary prophylaxis, and the evidence is equivocal. 1

Recommended Antibiotic Regimens

First-Line Options:

• Norfloxacin 400 mg orally once daily (preferred in European guidelines) 1, 2, 3
• Ciprofloxacin 500 mg orally once daily (acceptable alternative, particularly in regions where norfloxacin is unavailable) 1, 2, 4

Alternative Option:

• Trimethoprim-sulfamethoxazole (800/160 mg) once daily (for patients intolerant to fluoroquinolones) 2, 4

Do not use weekly ciprofloxacin regimens - while one study showed weekly ciprofloxacin was non-inferior to daily norfloxacin 5, guidelines consistently recommend daily dosing, and weekly regimens may promote quinolone resistance. 2, 4

Evidence Supporting Primary Prophylaxis

The strongest evidence comes from a double-blind, placebo-controlled trial in patients with severe liver disease (Child-Pugh ≥9, bilirubin ≥3 mg/dL) and ascitic fluid protein <15 g/L, which demonstrated that norfloxacin: 1

• Reduced 1-year probability of developing SBP from 61% to 7% 1, 3, 4
• Improved 3-month survival from 62% to 94% 1, 2, 3
• Reduced risk of hepatorenal syndrome from 41% to 28% 1, 3, 4

However, the 1-year survival difference did not reach statistical significance (60% vs 48%, p=0.05), highlighting that prophylaxis primarily prevents SBP rather than dramatically altering long-term mortality. 1

Duration of Prophylaxis

• Continue prophylaxis until liver transplantation, death, or resolution of ascites 2, 6
• The optimal duration has not been definitively established in clinical trials 1
• Some experts suggest prophylaxis could potentially be discontinued if liver function significantly improves, though this is not well-studied 1

Critical Warnings and Pitfalls

Antibiotic Resistance Concerns:

• Long-term quinolone use selects for resistant organisms and increases the risk of gram-positive infections (79% vs 33%), including MRSA 1, 4
• This underscores the importance of restricting prophylaxis to truly high-risk patients only 1
• Consider local resistance patterns when selecting antibiotics 2, 4

Fluoroquinolone Adverse Effects:

• Risk of tendon inflammation and rupture, particularly with renal impairment 2, 3, 4
• Discontinue immediately if tendon pain develops 2, 4
• Potential for irreversible musculoskeletal and neurological adverse effects 4

Additional Considerations:

• Restrict proton pump inhibitor use in cirrhotic patients, as PPIs may increase SBP risk 2, 3, 4
• Monitor renal function regularly in patients on prophylactic antibiotics 2, 3, 4
• Perform diagnostic paracentesis if clinical deterioration occurs (fever, abdominal pain, encephalopathy, worsening renal function, or unexplained leukocytosis) 1, 3, 4
• Increased risk of Clostridium difficile infection with long-term antibiotic use 3

When Primary Prophylaxis is NOT Clearly Indicated

For patients with ascitic fluid protein <15 g/L but without the additional high-risk features (advanced liver disease or renal impairment), the evidence is mixed. One study in moderate liver disease patients (Child-Pugh ~8.5) showed a trend toward benefit with ciprofloxacin (4% vs 14% SBP rate) but did not reach statistical significance. 1 In this population, clinical judgment is required, weighing individual risk factors against concerns about antibiotic resistance.