In a patient with liver cirrhosis, a white blood cell count of 15,000 cells/µL and a temperature of 99.3 °F, what empiric antibiotic therapy should be initiated for presumed spontaneous bacterial peritonitis?

Empiric Antibiotic Therapy for Suspected Spontaneous Bacterial Peritonitis in Cirrhosis

Perform diagnostic paracentesis immediately and initiate intravenous cefotaxime 2 grams every 8 hours (or ceftriaxone 2 grams once daily) without waiting for ascitic fluid results, given the elevated WBC and low-grade fever in this cirrhotic patient. 1, 2

Immediate Diagnostic Steps

• Obtain diagnostic paracentesis urgently in any cirrhotic patient with ascites who presents with peripheral leukocytosis (WBC 15,000), even with a temperature of only 99.3°F, as SBP can present with minimal or absent fever. 1

• Send ascitic fluid for: polymorphonuclear (PMN) cell count with differential, bacterial culture (inoculated into blood culture bottles at bedside), total protein, LDH, glucose, and Gram stain. 1, 2

• Obtain blood cultures before initiating antibiotics, as bacteremia occurs in a significant proportion of SBP cases. 1

Empiric Antibiotic Selection

First-line therapy:

• Cefotaxime 2 grams IV every 8 hours is the gold standard, with infection resolution rates of 77-98% and no nephrotoxicity. 1, 2, 3, 4

• Ceftriaxone 2 grams IV once daily (or 1 gram every 12 hours) is equally effective with resolution rates of 73-100% and offers convenient once-daily dosing. 1, 2

Critical point: Start antibiotics immediately after paracentesis is performed, even before PMN count results return, given the clinical suspicion (peripheral leukocytosis + low-grade fever). 1

Why Third-Generation Cephalosporins Are Preferred

• These agents provide optimal coverage against the most common SBP pathogens: E. coli (33-34% of cases), Klebsiella pneumoniae, and Streptococcus species. 2, 3, 5

• They achieve excellent ascitic fluid concentrations even in low-protein ascites. 2, 4

• Unlike aminoglycosides, they carry no nephrotoxicity risk—crucial in cirrhotic patients who are prone to hepatorenal syndrome. 1, 4

Adjunctive Albumin Therapy

Administer IV albumin if the patient has any high-risk features:

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

Dosing: 1.5 g/kg body weight within 6 hours of diagnosis, followed by 1.0 g/kg on day 3. 2

This regimen reduces mortality from 29% to 10% and prevents hepatorenal syndrome. 2

Treatment Duration and Monitoring

• Standard duration is 5 days for uncomplicated SBP; extending to 10 days offers no additional benefit. 1, 2

• Perform repeat paracentesis at 48 hours to assess treatment response. 1, 2

• Treatment success is defined as a ≥75% reduction in ascitic PMN count (i.e., PMN count drops to <25% of baseline). 2

• If PMN count fails to decrease by at least 25% at 48 hours, suspect treatment failure due to resistant organisms or secondary peritonitis and broaden coverage. 1, 2

Critical Caveats and Pitfalls

Do NOT use quinolones (ciprofloxacin, levofloxacin) as first-line therapy if:

• The patient has received quinolone prophylaxis (norfloxacin) previously—resistance rates are high. 2, 5
• The patient presents with severe disease: shock, renal failure, hepatic encephalopathy, GI bleeding, or ileus. 2
• The infection is hospital-acquired rather than community-acquired. 2

Suspect secondary bacterial peritonitis (requiring surgery) if:

• Ascitic PMN count is >1,000/mm³ 6
• Multiple organisms are seen on Gram stain or culture 1, 6
• Ascitic total protein ≥1 g/dL, LDH > upper limit of normal for serum, or glucose <50 mg/dL 1, 6
• Patient fails to improve clinically by 48 hours despite appropriate antibiotics 1

In these cases, obtain urgent CT imaging, add anaerobic coverage (e.g., metronidazole or switch to piperacillin-tazobactam), and consult surgery immediately. 1, 6

Emerging resistance patterns:

• Recent data show an increasing incidence of Gram-positive organisms (coagulase-negative Staphylococcus, 19.7% of isolates) that are less susceptible to cephalosporins (44% susceptibility vs. 82% for E. coli). 5
• If cultures grow Gram-positive cocci and the patient is not improving, consider adding vancomycin or switching to a broader agent. 5

Rare but important: Listeria monocytogenes SBP presents with extremely high ascitic leukocyte counts and is resistant to cephalosporins; if suspected (especially with very high PMN counts or lack of response), add ampicillin. 7

Post-Treatment Prophylaxis

After successful treatment, initiate indefinite secondary prophylaxis:

• Norfloxacin 400 mg orally once daily (reduces recurrence from 68% to 20%) 2
• Alternative: ciprofloxacin 500 mg orally once daily or co-trimoxazole 800/160 mg once daily 2
• Continue until liver transplantation or death 2