What is the recommended empiric antibiotic regimen (including alternatives for severe β‑lactam allergy or high ESBL prevalence) and albumin dosing for a patient with suspected spontaneous bacterial peritonitis?

Empiric Antibiotic Regimen for Suspected Spontaneous Bacterial Peritonitis

Initiate cefotaxime 2 g IV every 8 hours immediately after diagnostic paracentesis without waiting for culture results, combined with intravenous albumin 1.5 g/kg within 6 hours of diagnosis followed by 1.0 g/kg on day 3. 1, 2, 3

First-Line Antibiotic Therapy

Standard Regimen (Community-Acquired SBP)

• Cefotaxime 2 g IV every 8 hours for 5 days is the most extensively studied regimen with infection resolution rates of 77–98% 1, 2, 3
• Alternative: Ceftriaxone 2 g IV once daily (or 1 g every 12 hours) for 5 days achieves equivalent efficacy with resolution rates of 73–100% 1, 2
• Both third-generation cephalosporins provide adequate coverage for the most common pathogens: E. coli, Klebsiella pneumoniae, and Streptococcus species 2, 4

Alternative Oral Therapy (Highly Selected Patients Only)

• Oral ofloxacin 400 mg twice daily may replace IV cephalosporins only in patients meeting all of the following criteria: 2
  • No prior quinolone exposure or current quinolone prophylaxis 1, 2
  • No vomiting, shock, or hemodynamic instability 2
  • No grade II or higher hepatic encephalopathy 2
  • Serum creatinine < 3 mg/dL 2
  • No severe liver disease features 2
• This oral strategy applies to approximately 60% of SBP cases 2

Mandatory Albumin Therapy

Albumin administration is not optional—it provides mortality benefit independent of antibiotics and must be given to all patients with high-risk features. 1, 2, 3

Dosing Protocol

• 1.5 g/kg body weight IV within 6 hours of diagnosis 1, 2, 3
• 1.0 g/kg IV on day 3 1, 2, 3

High-Risk Features Mandating Albumin

• Serum creatinine ≥ 1 mg/dL 1, 2
• Blood urea nitrogen ≥ 30 mg/dL 1, 2
• Total bilirubin ≥ 4 mg/dL 1, 2

Mortality Benefit

• Reduces in-hospital mortality from 29% to 10% 1, 2, 3
• Decreases type 1 hepatorenal syndrome from 30% to 10% 1, 2, 3
• Albumin is superior to hydroxyethyl starch for this indication 2

Regimens for Severe β-Lactam Allergy

Quinolone Option (If No Prior Quinolone Exposure)

• Ciprofloxacin 200 mg IV every 12 hours for 7 days achieves 76% resolution rates 2
• Switch therapy: 200 mg IV every 12 hours for 2 days, then 500 mg PO every 12 hours for 5 days is cost-effective with equivalent efficacy 2

Critical Contraindications to Quinolones

Do not use quinolones as first-line therapy in: 1, 2

• Patients currently on norfloxacin or ciprofloxacin prophylaxis (high resistance rates) 1, 2
• Nosocomial SBP 1, 2
• Areas with high quinolone resistance 1
• Severe presentations: septic shock, renal failure, hepatic encephalopathy, GI bleeding, or ileus 2

Regimens for High ESBL Prevalence or Nosocomial SBP

Nosocomial or Healthcare-Associated SBP

For nosocomial SBP, third-generation cephalosporins have only 25% efficacy due to resistant organisms. 5

• Meropenem 1 g IV every 8 hours plus daptomycin 6 mg/kg/day achieves 86.7% resolution versus 25% with ceftazidime in nosocomial SBP 5
• Alternative: Piperacillin-tazobactam 4.5 g IV every 6 hours provides broader coverage 6
• Consider carbapenem monotherapy if gram-positive coverage is less of a concern 6

Risk Factors for Resistant Organisms

• Hospital-acquired SBP (>48 hours after admission) 2, 5
• Recent antibiotic exposure (especially quinolones) 1, 2
• Healthcare-associated infection 6, 5
• Known ESBL colonization or prior ESBL infection 2

Treatment Duration and Monitoring

Standard Duration

• 5 days of antibiotic therapy is sufficient for uncomplicated SBP—equally effective as 10 days 1, 2, 7
• Extend beyond 5 days only if clinical response is inadequate or cultures reveal resistant organisms 2

Mandatory 48-Hour Assessment

• Repeat paracentesis at 48 hours to assess treatment response 1, 2, 3
• Treatment success: Ascitic PMN count decreases to < 25% of pre-treatment value (i.e., ≥ 75% reduction) 1, 2, 3
• Treatment failure: PMN count fails to decrease by at least 25% or clinical deterioration 1, 2, 3

Response to Treatment Failure

If PMN count fails to drop by ≥ 25% at 48 hours: 1, 2, 3

• Broaden antibiotic coverage based on culture sensitivities 1, 2
• Obtain abdominal CT imaging to rule out secondary bacterial peritonitis 1, 3
• Consider surgical consultation 1, 3

Critical Pitfalls to Avoid

Distinguishing SBP from Secondary Peritonitis

Suspect secondary peritonitis (not SBP) if ≥ 2 of the following are present: 2, 3

• Ascitic fluid total protein > 1 g/dL 2, 3
• Ascitic fluid LDH > upper limit of normal for serum 2, 3
• Ascitic fluid glucose < 50 mg/dL 2, 3
• Polymicrobial culture growth 2, 3
• PMN count > 1,000/mm³ 3

If secondary peritonitis is suspected: 2, 3

• Add anaerobic antimicrobial coverage (e.g., metronidazole) 2
• Obtain urgent abdominal CT imaging 1, 3
• Request immediate surgical consultation 1, 3

Timing Is Critical

• Each hour of delay in initiating antibiotics increases in-hospital mortality by 3.3–10% in cirrhotic patients with septic shock 1, 3
• Begin empiric therapy immediately after diagnostic paracentesis—do not wait for culture results 1, 2, 3

Culture Technique Matters

• Inoculate at least 10 mL of ascitic fluid into blood culture bottles at bedside before starting antibiotics to increase culture sensitivity to > 90% 1, 3
• Simultaneously obtain blood cultures before antibiotic initiation 1, 3

Post-Treatment Management

Secondary Prophylaxis (Indefinite)

All patients surviving SBP require lifelong secondary prophylaxis until liver transplantation or ascites resolution: 2, 3

• Norfloxacin 400 mg PO daily reduces 1-year SBP recurrence from 68% to 20% 2
• Alternative: Ciprofloxacin 500 mg PO daily 2
• Continue indefinitely—do not discontinue prophylaxis 2

Prognosis

• Despite appropriate therapy, in-hospital mortality remains approximately 20% due to underlying liver disease 1, 3
• One-year survival after SBP hospitalization is approximately 34% 1
• All patients recovering from SBP should be assessed for liver transplantation eligibility 1