Do cirrhotic patients with ascites who have had spontaneous bacterial peritonitis require secondary antibiotic prophylaxis, and what regimen is recommended?

Secondary Prophylaxis for Spontaneous Bacterial Peritonitis

Yes, all cirrhotic patients who survive an episode of SBP absolutely require indefinite secondary antibiotic prophylaxis until liver transplantation or death. 1, 2

The Evidence for Secondary Prophylaxis

The rationale for this strong recommendation is compelling:

• Without prophylaxis, the 1-year recurrence rate of SBP is approximately 70%, making recurrence nearly inevitable 1
• Survival after an episode of SBP is dismal: only 30-50% at 1 year and 25-30% at 2 years 1
• Norfloxacin prophylaxis dramatically reduces recurrence from 68% to 20% in the only randomized, double-blind, placebo-controlled trial of secondary prophylaxis 1, 2

Recommended Prophylactic Regimens

First-line option:

• Norfloxacin 400 mg once daily is the most extensively studied and preferred regimen 1, 2

Alternative regimens (when norfloxacin is unavailable, as in the UK):

• Ciprofloxacin 500 mg once daily 1, 2
• Co-trimoxazole (800 mg sulfamethoxazole/160 mg trimethoprim) once daily 1

Duration of Prophylaxis

Prophylaxis must continue indefinitely until one of three endpoints 1, 2:

1. Liver transplantation
2. Death
3. Possibly if significant improvement in liver disease occurs (though no specific criteria exist for discontinuation) 2

There are no randomized trials addressing optimal duration, but the consensus is clear: do not stop prophylaxis 2

Critical Caveats and Pitfalls

Antibiotic Resistance Concerns

• Long-term quinolone prophylaxis increases risk of quinolone-resistant and Gram-positive bacterial infections 3, 4
• If SBP recurs while on quinolone prophylaxis, do not use quinolones for treatment—switch to third-generation cephalosporins (cefotaxime or ceftriaxone) 1, 2
• Emerging data suggest rifaximin may be superior to norfloxacin for secondary prophylaxis, with one RCT showing lower recurrence (3.88% vs 14.13%) and mortality (13.74% vs 24.43%), though additional prospective studies are needed before changing practice 1, 4

Monitoring Requirements

• Maintain high clinical suspicion for infection despite prophylaxis, as breakthrough infections occur 3
• Perform diagnostic paracentesis immediately if any signs of infection develop (fever, abdominal pain, encephalopathy, renal dysfunction) 1
• Consider proton pump inhibitor discontinuation if possible, as PPI use may increase SBP risk 1

When to Suspect Treatment Failure

If a patient on prophylaxis develops SBP, suspect:

• Quinolone-resistant organisms (most common) 1, 3
• Gram-positive bacteria (increasingly prevalent with long-term prophylaxis) 3
• Multidrug-resistant organisms, particularly in healthcare-associated infections 1

In these cases, empiric therapy must be broadened beyond quinolones, typically to third-generation cephalosporins or broader-spectrum agents based on local resistance patterns 1, 2