What antibiotics have good biliary penetration?

Antibiotics with Good Biliary Penetration

The antibiotics with the best biliary penetration include piperacillin-tazobactam, fluoroquinolones (ciprofloxacin, levofloxacin), ceftriaxone, tigecycline, and amoxicillin-clavulanate, according to the 2020 World Society of Emergency Surgery guidelines. 1

First-Tier Antibiotics (Excellent Biliary Penetration)

The following antibiotics achieve bile-to-serum concentration ratios ≥5, indicating excellent biliary penetration 1:

• Piperacillin-tazobactam - Recommended as first-line therapy for complicated biliary infections 1, 2
• Ciprofloxacin - Achieves high biliary concentrations and is present in active form in bile 3
• Levofloxacin - Similar penetration profile to ciprofloxacin 1
• Ceftriaxone - Third-generation cephalosporin with good biliary excretion 1
• Tigecycline - Broad-spectrum agent with excellent tissue penetration 1
• Amoxicillin-clavulanate - Suitable for mild-to-moderate infections 1, 2
• Ampicillin-sulbactam - Good penetration but increasing resistance concerns 1

Second-Tier Options (Moderate to Good Penetration)

Additional antibiotics with favorable biliary characteristics include 4:

• Carbapenems (meropenem, imipenem-cilastatin, ertapenem) - Excellent for severe infections despite variable biliary data 2
• Cefoperazone - Shows superior biliary excretion compared to other cephalosporins 5
• Cefbuperazone - Maintains adequate biliary concentrations even with obstruction 5

Critical Clinical Caveat: Biliary Obstruction

In patients with obstructed bile ducts, biliary penetration of ALL antibiotics is significantly impaired, and effective bile concentrations are reached in only a minority of patients. 1, 6 This is a crucial consideration because:

• Ciprofloxacin achieves bile-to-plasma ratios >1 in only 35% of obstructed patients 6
• Cefotaxime performs even worse, with adequate ratios in only 9% of obstructed cases 6
• Biliary drainage is essential and antibiotics alone are insufficient without addressing the obstruction 7, 2

Practical Selection Algorithm

For Community-Acquired Biliary Infections (Non-Critically Ill):

• First choice: Ampicillin-sulbactam or amoxicillin-clavulanate 2
• Alternative: Ciprofloxacin or levofloxacin (reserve due to resistance concerns) 2

For Healthcare-Associated or Severe Infections:

• First choice: Piperacillin-tazobactam 1, 2
• Alternatives: Carbapenems (meropenem, imipenem-cilastatin, ertapenem) 2
• For septic shock: Add amikacin for enhanced gram-negative coverage 2

Special Populations:

• Immunocompromised patients: Presume Enterococcus coverage and add ampicillin or vancomycin 1
• Biliary-enteric anastomosis: Add metronidazole for anaerobic coverage 2
• Previous biliary instrumentation: Consider fourth-generation cephalosporins 2

Antibiotics to Avoid

The following have poor biliary penetration and should not be relied upon for biliary infections 4:

• Amoxicillin (without clavulanate)
• Cefadroxil
• Cefoxitin
• Gentamicin
• Amikacin (except as adjunctive therapy in septic shock)
• Trimethoprim-sulfamethoxazole

Important Limitations

Serum bilirubin, alkaline phosphatase, or gamma-glutamyl-transpeptidase levels cannot predict biliary antibiotic penetration. 6 Therefore, selection should be based on:

1. Severity of infection 1
2. Presence or absence of biliary obstruction 1, 6
3. Healthcare-associated vs. community-acquired infection 1
4. Local resistance patterns 1

The single most important factor for successful treatment is ensuring adequate biliary drainage in addition to appropriate antibiotics. 7, 2 Delaying drainage in severe cholangitis while relying on antibiotics alone is a potentially fatal error 2.