Role of Rifaximin in Prevention of Spontaneous Bacterial Peritonitis
Rifaximin cannot currently be recommended as an alternative to norfloxacin for secondary prophylaxis of SBP, despite some promising evidence, and no recommendation can be made regarding its use in patients already taking rifaximin for hepatic encephalopathy prevention. 1
Current Guideline Recommendations
Secondary Prophylaxis (After Prior SBP Episode)
Norfloxacin 400 mg orally once daily remains the standard of care for patients who have recovered from an episode of SBP, reducing recurrence from 68% to 20% at one year. 1, 2
The 2018 EASL guidelines explicitly state that rifaximin cannot be recommended as an alternative to norfloxacin for secondary prophylaxis, despite some promising evidence. 1
Where norfloxacin is unavailable (such as in the UK), ciprofloxacin 500 mg once daily is used as an alternative, though direct evidence supporting this regimen is lacking. 1
Primary Prophylaxis (No Prior SBP)
Rifaximin has no established role in primary prophylaxis of SBP. 1
Norfloxacin 400 mg daily is recommended for high-risk patients with low ascitic fluid protein (<1.5 g/dL) plus advanced liver failure (Child-Pugh ≥9 with bilirubin ≥3 mg/dL) or renal impairment (creatinine ≥1.2 mg/dL). 1, 2
The Clinical Dilemma: Rifaximin for Hepatic Encephalopathy
Unresolved Questions
The guidelines acknowledge a significant clinical gap: many patients receive rifaximin to prevent recurrent hepatic encephalopathy, but there is no data to guide SBP prophylaxis decisions in these patients. 1
Specifically, it remains unknown whether:
- Norfloxacin prophylaxis should be started in patients already taking rifaximin for hepatic encephalopathy prevention 1
- Norfloxacin prophylaxis should be stopped in patients who require rifaximin for hepatic encephalopathy 1
- Combined therapy with norfloxacin and rifaximin offers benefits or causes harm 1
Emerging Research Evidence (Not Yet Guideline-Endorsed)
Secondary Prophylaxis Studies
While guidelines do not endorse rifaximin, newer research suggests potential benefit:
A 2022 randomized controlled trial found rifaximin superior to norfloxacin for secondary prophylaxis, with SBP recurrence of 7% versus 39% (p=0.004), and also reduced hepatic encephalopathy episodes (23.1% vs. 51.5%, p=0.02). 3
A single-center open-label trial showed rifaximin had lower 6-month SBP recurrence compared with norfloxacin (4% vs. 14%). 1
A 2017 systematic review concluded that rifaximin appears to be a reasonable alternative to norfloxacin, though evidence quality was moderate. 4
Combination Therapy
One study found alternating norfloxacin and rifaximin showed superior prophylaxis compared to either agent alone (74.7% vs. 56.4% vs. 68.3%, p<0.048). 5
A meta-analysis showed rifaximin plus norfloxacin reduced SBP incidence (RR 0.58,95% CI 0.37-0.92, p=0.02) and hepatic encephalopathy (RR 0.38,95% CI 0.17-0.84, p=0.02) compared to norfloxacin alone. 6
Important Caveats and Pitfalls
Guideline-Research Discordance
The most recent high-quality guidelines (2018 EASL, 2021 AASLD, 2021 BSG) do not endorse rifaximin for SBP prophylaxis, despite newer research showing potential benefit. 1 This reflects the conservative approach of guideline committees requiring more robust prospective data before changing practice recommendations.
Resistance Concerns
Long-term fluoroquinolone use raises concerns about bacterial resistance and emergence of multidrug-resistant organisms. 1, 2
Quinolone prophylaxis is less effective in patients colonized with multidrug-resistant organisms. 1
Rifaximin Limitations
Rifaximin may not prevent all SBP cases, as demonstrated by a case report of Pasteurella multocida SBP occurring despite rifaximin prophylaxis. 7
The drug's efficacy against gram-positive organisms and multidrug-resistant organisms is uncertain. 1
Drug Interactions
- Proton pump inhibitors may increase SBP risk and should be restricted to clear indications in patients requiring SBP prophylaxis. 1, 2
Practical Clinical Approach
Until prospective studies provide definitive evidence, follow guideline recommendations:
For secondary prophylaxis: Use norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily if norfloxacin unavailable). 1, 2
For patients already on rifaximin for hepatic encephalopathy who develop SBP: Add norfloxacin for secondary prophylaxis, as there is no evidence to support rifaximin monotherapy for this indication. 1
For primary prophylaxis: Use norfloxacin in high-risk patients; rifaximin has no established role. 1, 2
Continue prophylaxis indefinitely until liver transplantation or resolution of ascites. 2