Three Main Reasons for Prophylaxis in Patients with Cirrhosis
Antibiotic prophylaxis in cirrhosis is indicated for three specific high-risk scenarios: patients with acute gastrointestinal hemorrhage, patients with prior spontaneous bacterial peritonitis (secondary prophylaxis), and select high-risk patients with low ascitic protein who have never had SBP (primary prophylaxis). 1
1. Acute Gastrointestinal Hemorrhage
All cirrhotic patients with acute GI bleeding require antibiotic prophylaxis regardless of the presence of ascites. 1
- Bacterial infections occur in 25-65% of cirrhotic patients with GI bleeding, with the highest incidence in those with advanced cirrhosis (Child B/C) or severe hemorrhage. 1
- Infections in this setting increase failure to control bleeding, rebleeding rates, and hospital mortality. 1
- Antibiotic prophylaxis significantly decreases both severe infections (SBP and/or septicemia) and mortality. 1
Recommended regimens:
- For advanced cirrhosis (Child B/C) or settings with high quinolone resistance: IV ceftriaxone 1g daily for 7 days is superior to oral norfloxacin in preventing infections. 1, 2, 3
- For less severe disease (Child A): Oral norfloxacin 400 mg twice daily for 7 days is an acceptable alternative. 1, 2
2. Secondary Prophylaxis (Prior Episode of SBP)
Patients who survive an episode of SBP have a 70% cumulative recurrence rate at 1 year and require long-term antibiotic prophylaxis. 1
- Survival probability is only 30-50% at 1 year and 25-30% at 2 years after an SBP episode. 1
- Norfloxacin 400 mg daily reduces SBP recurrence from 68% to 20% in randomized controlled trials. 1
- All patients with prior SBP should also be evaluated for liver transplantation due to poor long-term survival. 2
Recommended regimens:
- Continuous oral norfloxacin 400 mg daily or ciprofloxacin 500 mg once daily. 2
- Continue prophylaxis indefinitely or until liver transplantation. 1
3. Primary Prophylaxis (High-Risk Patients Without Prior SBP)
Primary prophylaxis should be offered to patients at highest risk, though this remains the most controversial indication. 1
High-risk criteria vary by guideline society:
- NICE (2016): Ascitic protein ≤15 g/L (1.5 g/dL) with no history of SBP. 1
- EASL: Child-Pugh score ≥9 AND serum bilirubin ≥3 mg/dL, with either impaired renal function OR hyponatraemia AND ascitic fluid protein <15 g/L. 1
- AASLD: Ascitic fluid protein <1.5 g/dL together with impaired renal function OR liver failure. 1
Important caveats:
- The large NORFLOCIR trial showed norfloxacin did not reduce 6-month mortality in advanced cirrhosis, though post-hoc analysis suggested benefit in patients with low ascitic protein. 1
- Three large cohorts failed to replicate the association between low ascitic protein and SBP incidence. 1
- Long-term fluoroquinolone use increases risks of antibiotic resistance, Clostridium difficile infection, and potentially disabling musculoskeletal/nervous system side effects (particularly with renal impairment). 1, 2
- Norfloxacin is not widely available in the UK. 1
Given these uncertainties, primary prophylaxis should be reserved for patients meeting multiple high-risk criteria rather than applied broadly based on ascitic protein alone. 1
Critical Considerations
Emerging resistance patterns are shifting the bacterial landscape: Long-term quinolone prophylaxis increases gram-positive infections (including MRSA) and multidrug-resistant organisms. 2 Local bacterial resistance patterns should guide antibiotic selection. 1, 2
The three indications have vastly different evidence quality: GI bleeding prophylaxis is established practice with strong evidence 1, secondary prophylaxis has solid randomized trial support 1, while primary prophylaxis remains controversial with conflicting data and should be applied selectively. 1