For a cirrhotic patient with suspected spontaneous bacterial peritonitis and a high ascitic fluid white‑cell count, which antibiotic should be used as first‑line empiric therapy?

First-Line Antibiotic for Suspected Spontaneous Bacterial Peritonitis in Cirrhosis

Intravenous cefotaxime 2 grams every 8 hours is the preferred first-line empiric antibiotic for cirrhotic patients with suspected spontaneous bacterial peritonitis and high ascitic fluid white-cell counts. 1

Primary Treatment Recommendation

• Cefotaxime 2 g IV every 8 hours remains the gold standard, supported by the highest quality evidence with infection resolution rates of 77-98% 1, 2
• This regimen achieves excellent ascitic fluid concentrations (20-fold killing power after one dose) and covers the three most common pathogens: E. coli, Klebsiella pneumoniae, and Streptococcus species 1, 3
• Treatment duration should be 5 days for uncomplicated cases, as this has been proven equally effective to 10-day courses in randomized controlled trials 1, 2

Equally Effective Alternative

• Ceftriaxone 1-2 g IV every 12-24 hours provides comparable efficacy with resolution rates of 73-100% 1, 2, 4
• Ceftriaxone offers the convenience of once or twice-daily dosing, though it is highly protein-bound (a theoretical concern in low-protein ascites that has not proven clinically significant) 1, 2

Critical Adjunctive Therapy: Albumin

You must administer intravenous albumin concurrently with antibiotics in high-risk patients to reduce mortality from 29% to 10% 2, 4, 5

• Give 1.5 g/kg body weight within 6 hours of diagnosis, followed by 1.0 g/kg on day 3 2, 4
• High-risk features requiring albumin include: serum creatinine ≥1 mg/dL, blood urea nitrogen ≥30 mg/dL, or total bilirubin ≥4 mg/dL 2, 4
• Albumin prevents hepatorenal syndrome (reduces incidence from 33% to 10%) and improves survival beyond antibiotic effects alone 4, 5

When NOT to Use Cefotaxime/Ceftriaxone as First-Line

Avoid third-generation cephalosporins in these specific scenarios:

• Nosocomial or healthcare-associated SBP: Use broader coverage with meropenem 1 g IV every 8 hours plus daptomycin 6 mg/kg/day in settings with high multidrug-resistant organism prevalence 5
• Patients on quinolone prophylaxis: These patients likely harbor quinolone-resistant organisms and require alternative coverage 2, 4
• Recent hospitalization or ICU stay: Consider broader empiric coverage due to increased risk of resistant organisms 5, 6

Oral Alternative (Highly Selected Patients Only)

• Oral ofloxacin 400 mg twice daily may replace IV cefotaxime in approximately 60% of patients who meet ALL of the following criteria 1, 2:
  • No prior quinolone exposure
  • No vomiting
  • No shock or sepsis
  • No grade II or higher hepatic encephalopathy
  • Serum creatinine <3 mg/dL
  • Community-acquired infection 1, 5

Monitoring Treatment Response

• Perform repeat paracentesis at 48 hours to assess treatment efficacy 2, 4, 5
• Treatment success is defined as a ≥75% reduction in ascitic PMN count (i.e., PMN count <25% of baseline) 2, 5
• If PMN count fails to decrease by at least 25% at 48 hours, suspect treatment failure and broaden antimicrobial coverage 2, 5

Critical Pitfalls to Avoid

Never delay antibiotics waiting for culture results—the ascitic fluid PMN count is rapidly available and sufficiently accurate to guide empiric therapy; delaying treatment may result in death from overwhelming infection 1, 4, 5

Do not omit albumin in high-risk patients—this is not optional supportive care but rather a mortality-reducing intervention with Level A evidence 2, 4

Rule out secondary peritonitis by ordering ascitic fluid total protein, LDH, and glucose 1, 4. Secondary peritonitis is suspected when ≥2 of these criteria are met: total protein ≥1 g/dL, LDH >upper limit of normal for serum, glucose <50 mg/dL 1, 4. If secondary peritonitis is suspected, add anaerobic coverage and obtain surgical consultation 1

Avoid aminoglycosides (e.g., ampicillin plus tobramycin) as they are inferior to cefotaxime and carry nephrotoxicity risk 1, 5

Why Cefotaxime Remains Superior

Despite the availability of alternatives, cefotaxime is the most extensively studied antibiotic for SBP with decades of clinical trial data demonstrating superior outcomes compared to older regimens 1, 3. The American Association for the Study of Liver Diseases and European Association for the Study of the Liver both prioritize third-generation cephalosporins as first-line agents due to broader coverage and consistently higher infection resolution rates 1, 2, 5