What oral antibiotics are recommended for Spontaneous Bacterial Peritonitis (SBP) prophylaxis?

Oral Antibiotics for SBP Prophylaxis

Norfloxacin 400 mg once daily is the first-line oral antibiotic for SBP prophylaxis in cirrhotic patients, with ciprofloxacin 500 mg once daily as an acceptable alternative when norfloxacin is unavailable. 1, 2, 3

Secondary Prophylaxis (After Prior SBP Episode)

All patients who have recovered from SBP require indefinite antibiotic prophylaxis due to the extremely high recurrence risk of approximately 68-70% at one year without treatment. 1, 2, 3

Recommended Regimens:

• Norfloxacin 400 mg orally once daily - reduces recurrence from 68% to 20% and improves 3-month survival from 62% to 94% 1, 2, 3
• Ciprofloxacin 500 mg orally once daily - acceptable alternative when norfloxacin unavailable 2, 3
• Trimethoprim-sulfamethoxazole (800/160 mg) once daily - alternative option but associated with increased adverse events compared to norfloxacin 1, 3, 4

Critical point: Prophylaxis should continue indefinitely until liver transplantation or complete resolution of ascites, and all patients with prior SBP should be evaluated for transplantation given poor long-term survival. 2, 3

Primary Prophylaxis (No Prior SBP)

Primary prophylaxis remains controversial, with recent guidelines showing divergent recommendations. 1 The 2021 British Society of Gastroenterology guidelines note that the large NORFLOCIR trial failed to show mortality benefit with norfloxacin in advanced cirrhosis. 1

High-Risk Criteria Requiring Prophylaxis:

Norfloxacin 400 mg once daily is recommended for patients meeting ALL of the following: 1, 2, 3

• Ascitic fluid protein <15 g/L (1.5 g/dL) AND
• Child-Pugh score ≥9 with serum bilirubin ≥3 mg/dL AND
• At least one of: impaired renal function (creatinine ≥1.2 mg/dL), hyponatremia (sodium ≤130 mEq/L), or blood urea nitrogen ≥25 mg/dL 1, 2

Important caveat: Recent evidence questions whether low ascitic fluid protein alone predicts SBP risk, with three large cohorts failing to replicate this association. 1 Therefore, primary prophylaxis should be reserved only for patients with multiple high-risk features, not based solely on low protein levels.

Prophylaxis During Gastrointestinal Bleeding

All cirrhotic patients with acute GI bleeding require antibiotic prophylaxis regardless of ascites presence, as bacterial infections occur in 25-65% and significantly increase mortality. 2

Regimen Selection:

• Advanced/severe liver disease: IV ceftriaxone 1g daily for 7 days is superior to oral quinolones 1, 2
• Less severe disease: Norfloxacin 400 mg orally twice daily for 7 days is acceptable 2

This is the most frequently overlooked indication for prophylaxis in clinical practice. 5

Alternative Agents and Emerging Data

Rifaximin:

Rifaximin cannot be recommended for SBP prophylaxis based on current guidelines, despite some promising research data. 6 The 2021 EASL, AASLD, and BSG guidelines explicitly do not endorse rifaximin for this indication. 6 While one trial showed lower 6-month SBP recurrence with rifaximin versus norfloxacin (4% vs 14%), this has not been validated in larger studies or incorporated into guidelines. 6, 7, 8

Trimethoprim-Sulfamethoxazole:

One trial demonstrated efficacy comparable to norfloxacin, but with higher adverse event rates. 1, 7 This can be considered when quinolones are contraindicated, though it is not first-line. 3

Critical Pitfalls and Safety Concerns

Fluoroquinolone Risks:

• Long-term quinolone use increases risk of multidrug-resistant organisms and shifts infections toward gram-positive bacteria including MRSA 2, 3, 6
• The 2019 MHRA warning highlights rare but serious musculoskeletal and neurological side effects with fluoroquinolones, particularly in patients with renal impairment 1
• Monitor for tendon pain or inflammation and discontinue immediately if these occur 3

Resistance Patterns:

• Always consider local bacterial resistance patterns when selecting antibiotics 2, 3
• Avoid weekly ciprofloxacin regimens - while one study suggested non-inferiority to daily norfloxacin, this may promote quinolone resistance 7
• Quinolone prophylaxis becomes less effective in patients colonized with multidrug-resistant organisms 6

Monitoring Requirements:

• Regular renal function monitoring is essential in all patients on prophylactic antibiotics 3
• Restrict proton pump inhibitor use as PPIs may increase SBP risk 3, 6
• Perform diagnostic paracentesis immediately with any clinical deterioration 3

Adherence Issues:

A retrospective study found that 62% of SBP cases were "preventable" due to failure to prescribe indicated prophylaxis, with GI hemorrhage being the most frequently overlooked indication. 5 Additionally, only one-third of patients who survived SBP received appropriate long-term outpatient prophylaxis after discharge. 5

Practical Algorithm

For patients with prior SBP:

1. Start norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily if unavailable)
2. Continue indefinitely until transplant or ascites resolution
3. Refer for transplant evaluation

For patients without prior SBP:

1. Assess for GI bleeding → if present, use IV ceftriaxone (severe disease) or norfloxacin 400 mg BID × 7 days (less severe)
2. If no bleeding, assess: ascitic fluid protein <15 g/L + Child-Pugh ≥9 + bilirubin ≥3 mg/dL + renal dysfunction/hyponatremia → if ALL present, consider norfloxacin 400 mg daily
3. If criteria not met, prophylaxis generally not indicated given resistance concerns and lack of proven mortality benefit 1