What are the indications for primary prophylaxis of Spontaneous Bacterial Peritonitis (SBP) in patients with cirrhosis and ascites?

Indications for Primary Prophylaxis of Spontaneous Bacterial Peritonitis

Primary prophylaxis for SBP should be offered to high-risk cirrhotic patients with ascites who have ascitic fluid protein <15 g/L (1.5 g/dL) AND advanced liver disease, defined as Child-Pugh score ≥9 with serum bilirubin ≥3 mg/dL, OR impaired renal function (creatinine ≥1.2 mg/dL, BUN >25 mg/dL), OR hyponatremia (sodium ≤130 mEq/L). 1, 2

High-Risk Patient Criteria

The following patients should receive primary prophylaxis:

Criterion 1: Low Ascitic Fluid Protein

• Ascitic fluid total protein concentration <15 g/L (1.5 g/dL) 1, 2

PLUS at least ONE of the following:

Advanced Liver Disease:

• Child-Pugh score ≥9 points AND serum bilirubin ≥3 mg/dL 1, 2

Impaired Renal Function (any of the following):

• Serum creatinine ≥1.2 mg/dL 1, 2
• Blood urea nitrogen (BUN) >25 mg/dL 1, 2

Hyponatremia:

• Serum sodium ≤130 mEq/L 1, 2

Recommended Prophylactic Regimens

First-line agent:

• Norfloxacin 400 mg orally once daily until ascites resolves 1, 3, 2

Alternative agents (when norfloxacin unavailable):

• Ciprofloxacin 500 mg orally once daily 3, 2, 4
• Co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim) once daily 3

Evidence Supporting Primary Prophylaxis

Mortality benefit: In high-risk patients meeting the above criteria, norfloxacin improved 3-month survival from 62% to 94% (p=0.03) 1, 3, 2

SBP reduction: Norfloxacin reduced the 1-year probability of developing SBP from 61% to 7% in patients with advanced liver disease and low ascitic protein 1, 3, 2

Hepatorenal syndrome prevention: Norfloxacin reduced the risk of hepatorenal syndrome from 41% to 28% 3, 2

Special Circumstance: Acute GI Bleeding

All cirrhotic patients with acute gastrointestinal bleeding require antibiotic prophylaxis regardless of ascitic fluid protein levels: 1, 5

• Advanced cirrhosis (Child-Pugh B/C): IV ceftriaxone 1g daily for 7 days 1, 3
• Less severe cirrhosis (Child-Pugh A): Norfloxacin 400 mg orally twice daily for 7 days 1, 5

Critical Warnings and Monitoring

Antibiotic resistance concerns: Long-term quinolone prophylaxis increases the risk of gram-positive infections and multidrug-resistant organisms 1, 3, 5, 2

Fluoroquinolone safety: Monitor for tendon pain or inflammation and discontinue immediately if these symptoms develop, particularly in patients with renal impairment 1

Renal function monitoring: Regular monitoring of renal function is essential in all patients receiving prophylactic antibiotics 3, 2

Avoid proton pump inhibitors: Restrict PPI use in cirrhotic patients as they may increase SBP risk 3, 2

Important Clinical Pitfalls

The NORFLOCIR trial controversy: A large 2021 placebo-controlled trial found that norfloxacin did not reduce 6-month mortality in patients with advanced cirrhosis, though post-hoc analyses suggested benefit in those with low ascitic protein 1

Guideline divergence: Despite the NORFLOCIR trial results, EASL, AASLD, and NICE guidelines continue to recommend primary prophylaxis for high-risk patients, emphasizing the importance of selecting only those meeting BOTH low ascitic protein AND additional high-risk criteria 1, 2

Not all low protein patients need prophylaxis: Three large cohorts failed to replicate an association between low ascitic protein alone and SBP incidence, reinforcing that additional risk factors (advanced liver disease, renal dysfunction, or hyponatremia) must be present 1

Norfloxacin availability: Norfloxacin is not widely available in the UK, making ciprofloxacin the practical alternative 1