What is the preferred antibiotic, cefazolin or ampicillin-sulbactam, for a patient with liver cancer and biliary risk factors undergoing Transarterial Chemoembolization (TACE)?

Cefazolin is the Preferred Antibiotic for TACE in Patients with Liver Cancer and Biliary Risk Factors

For patients with hepatocellular carcinoma and biliary risk factors undergoing TACE, cefazolin 2g IV as a single dose is the recommended first-line prophylactic antibiotic, with fluoroquinolones (levofloxacin or moxifloxacin) as acceptable alternatives. Ampicillin-sulbactam is not recommended due to high resistance rates among community-acquired E. coli and is notably absent from all major guideline recommendations for TACE prophylaxis. 1, 2

Why Cefazolin Over Ampicillin-Sulbactam

Guideline-Based Recommendations

• The 2023 Korean Liver Cancer Association guidelines explicitly state that first-generation cephalosporins (cefazolin) or fluoroquinolones are the appropriate prophylactic antibiotics for TACE, with no mention of ampicillin-sulbactam. 1
• Ampicillin-sulbactam is specifically discouraged by the Infectious Diseases Society of America for intra-abdominal infections due to high resistance rates among community-acquired E. coli, which shares similar pathogen profiles with post-TACE infections. 2
• The American College of Hepatology recommends cefazolin 2g IV as a single dose or fluoroquinolones (levofloxacin 300-500mg or moxifloxacin 400mg) for TACE prophylaxis, explicitly excluding ampicillin-sulbactam from recommended regimens. 2, 3

Target Pathogen Coverage

• Post-TACE liver abscesses are caused by gram-negative bacilli (E. coli, Proteus mirabilis), Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. 2, 3
• Cefazolin provides excellent coverage against these organisms and is FDA-approved for biliary tract infections due to E. coli, streptococci, P. mirabilis, and S. aureus. 4
• Ampicillin-sulbactam has significant resistance issues with E. coli, making it inferior for this indication. 2

Evidence Supporting Cefazolin

Large-Scale Efficacy Data

• A recent large-scale cohort study with propensity score analysis demonstrated that prophylactic antibiotics reduced liver abscess occurrence following TACE by two-thirds. 1
• Moxifloxacin monotherapy prevented liver abscess by 100% in retrospective studies, and an RCT showed levofloxacin is non-inferior to cefazolin. 1

Risk Stratification

• Patients with biliary risk factors absolutely require prophylactic antibiotics: biliary obstruction, bilioenteric anastomosis, or biliary stent across the ampulla of Vater. 1, 2, 3
• In the hepatologist survey, 60.9% of respondents indicated that patients with biliary risk factors are specifically indicated for preemptive antibiotic use. 1
• Post-TACE liver abscess occurs in 0.1-4.5% of cases overall, but risk increases substantially with biliary risk factors. 3

Practical Antibiotic Regimen

Initial Prophylaxis

• Administer cefazolin 2g IV as a single dose immediately before TACE. 1, 2, 3
• Alternative: Levofloxacin 500mg oral/IV or moxifloxacin 400mg oral/IV as a single dose. 1, 2

Post-Procedure Management

• Total antibiotic duration should not exceed 5-7 days from the time of TACE. 2, 3, 5
• At 24-48 hours post-TACE, if the patient is clinically stable, either discontinue antibiotics entirely or transition to oral fluoroquinolone for 3-5 additional days (total 5-7 days). 2
• Long-term antibiotic use beyond two weeks provides no additional benefit in preventing liver abscess compared to short-term use. 1

Step-Down Options for Biliary Risk Patients

• Levofloxacin 500mg orally once daily for 3-5 additional days (non-inferior to cefazolin based on RCT evidence). 1, 2
• Moxifloxacin 400mg orally once daily for 3-5 additional days (100% prevention rate in retrospective studies). 1, 2

Common Pitfalls to Avoid

Do Not Use Ampicillin-Sulbactam

• Ampicillin-sulbactam is not recommended for TACE prophylaxis due to resistance patterns and absence from all guideline recommendations. 2
• The Infectious Diseases Society of America specifically recommends against using ampicillin-sulbactam for intra-abdominal infections due to high E. coli resistance rates. 2

Do Not Add Metronidazole

• Metronidazole is primarily for anaerobic coverage and is not indicated for TACE prophylaxis, as the target pathogens are adequately covered by cephalosporins and fluoroquinolones. 2, 5
• Adding metronidazole provides no benefit and adds unnecessary antibiotic exposure. 2, 5

Do Not Extend Prophylaxis Duration

• Prolonged antibiotic courses beyond 5-7 days provide no additional benefit and increase antimicrobial resistance risk. 1, 2, 5
• If a liver abscess develops post-TACE, this requires 4-6 weeks of therapeutic antibiotics, not extended prophylaxis. 2, 5

Verify Biliary Risk Factors on Pre-Treatment Imaging

• Operators must check pre-treatment CT or MRI for bilioenteric anastomosis or biliary stent to identify patients requiring prophylaxis. 1, 2
• The time interval between pre-treatment imaging and TACE should be within two months, ideally within one month. 1

Nuances in the Evidence

Debate on Universal Prophylaxis

• While 49.1% of hepatologists use prophylactic antibiotics for all or selected cases, the strongest evidence supports targeted prophylaxis for patients with biliary risk factors. 1
• Two small retrospective studies showed negative results for universal prophylaxis 6, 7, but the most recent large-scale cohort with propensity score analysis demonstrated clear benefit, particularly in high-risk patients. 1
• In patients with intact Sphincter of Oddi and no biliary instrumentation, infection risk is extremely low (0/232 infusions in one study), suggesting prophylaxis may not be necessary in this subgroup. 7

Route of Administration

• Oral fluoroquinolones are non-inferior to IV cephalosporins, making them practical alternatives for outpatient procedures or step-down therapy. 1, 2, 8
• No significant difference was found between oral and intravenous routes in comparative studies. 8