What antibiotics are contraindicated in patients with liver failure?

Antibiotics Contraindicated in Liver Failure

Several antibiotics should be avoided or used with extreme caution in patients with liver failure due to their potential for hepatotoxicity or altered metabolism. 1

Antibiotics to Avoid or Use with Extreme Caution

• Macrolides (erythromycin, clarithromycin) should be avoided as they can cause intrahepatic cholestasis and have significant hepatotoxic potential 1, 2
• Tetracyclines should be avoided as they can cause a syndrome mimicking acute fatty liver, with potential for severe hepatotoxicity 3
• Rifampicin requires significant dose adjustment or avoidance in severe liver impairment due to its hepatic metabolism 1
• Isoniazid should be avoided due to high risk of hepatotoxicity in patients with pre-existing liver disease 1
• Amoxicillin-clavulanate is the most frequent cause of drug-induced liver injury (DILI) related hospitalizations and should be used with extreme caution 4, 3
• Flucloxacillin ranks as the second highest cause of DILI in many countries and should be avoided 4, 3
• Sulfonamides (including sulfamethoxazole/trimethoprim) can cause severe hepatotoxicity, especially in immunocompromised patients 3
• Nitrofurantoin should be avoided as it can cause both acute cholestatic reactions and chronic hepatitis 3

Safer Antibiotic Options in Liver Failure

• Third-generation cephalosporins (ceftriaxone, cefotaxime) are generally safe and recommended as first-line options 1
• Piperacillin-tazobactam is considered safer in liver impairment 1
• Carbapenems can be used with appropriate dosing adjustments 1
• Fluoroquinolones can be used with caution and dose adjustment 1

Special Considerations for Different Types of Liver Disease

Acute Liver Failure (ALF)

• Empirical broad-spectrum antibiotics should be administered if there are signs of sepsis or worsening encephalopathy 5
• Non-absorbable antibiotics like rifaximin are not recommended to lower ammonia levels in ALF 5

Cirrhosis and Acute-on-Chronic Liver Failure (ACLF)

• For spontaneous bacterial peritonitis (SBP), cefotaxime is recommended as it covers 95% of flora isolated from ascitic fluid 1
• For upper gastrointestinal bleeding in cirrhotic patients, prophylactic antibiotics (typically third-generation cephalosporins) are recommended 1

Mechanisms of Antibiotic-Induced Liver Injury

• Antibiotic-related liver injuries can present as:

  • Cytotoxic hepatitis (isoniazid) 2
  • Intrahepatic cholestasis (macrolides, penicillins, clavulanic acid) 2
  • Mixed hepatitis (sulfonamides) 2
  • Chronic active hepatitis (nitrofurantoin) 2
  • Microvesicular steatosis (tetracycline) 2

• Most antibiotic-induced liver toxicity is idiosyncratic, occurring only in susceptible individuals 4, 2

Common Pitfalls and Caveats

• Cirrhotic patients have increased susceptibility to infections, with bacterial infections documented in 60-80% of patients with ALF 1
• The severity of antibiotic-induced DILI varies widely, with hepatocellular damage typically being more severe than cholestatic/mixed types 4
• Reduced drug metabolism in liver disease doesn't necessarily increase the frequency of hepatotoxicity, but can lead to drug accumulation and concentration-dependent adverse effects 6
• Some cephalosporins containing sulphydryl groups can inhibit vitamin K-dependent clotting factors, worsening coagulopathy in liver failure 2, 6

Monitoring Recommendations

• Monitor liver function tests before and during treatment with potentially hepatotoxic antibiotics 4
• Be vigilant for signs of worsening liver function including increasing jaundice, coagulopathy, or encephalopathy 5
• Consider therapeutic drug monitoring when available for antibiotics with narrow therapeutic windows 6