From the Guidelines
When antibiotics cause liver derangement, immediate discontinuation of the offending antibiotic is the primary treatment, as recommended by the most recent guidelines on the management of abnormal liver blood tests 1. The treatment approach for antibiotics causing liver derangement should prioritize the discontinuation of the hepatotoxic antibiotic and the selection of alternative antibiotics with less hepatotoxic potential.
- For mild liver enzyme elevations (less than 3 times upper limit of normal), close monitoring may be sufficient while continuing necessary antibiotics.
- For moderate to severe liver injury, supportive care includes maintaining hydration, correcting electrolyte imbalances, and monitoring coagulation parameters.
- N-acetylcysteine (NAC) at 150 mg/kg IV over 1 hour, followed by 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours may be beneficial in cases of severe drug-induced liver injury, though evidence is strongest for acetaminophen toxicity. Antibiotics commonly associated with liver injury include amoxicillin-clavulanate, fluoroquinolones, macrolides, and anti-tuberculosis drugs like isoniazid and pyrazinamide, as noted in the guidelines on the management of abnormal liver blood tests 1 and the official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America clinical practice guidelines: treatment of drug-susceptible tuberculosis 1. When selecting alternative antibiotics, consider options like cephalosporins, which generally have lower hepatotoxicity.
- Liver function should be monitored regularly during antibiotic therapy, especially in patients with pre-existing liver disease, advanced age, or those taking multiple medications.
- The mechanism of antibiotic-induced liver injury varies from direct hepatotoxicity to idiosyncratic immune-mediated reactions, which explains why treatment approaches must be individualized based on severity and presentation. The primary goal is to minimize liver injury while effectively treating the underlying infection, and this can be achieved by carefully selecting alternative antibiotics and closely monitoring liver function, as emphasized in the guidelines 1.
From the FDA Drug Label
The sites of the drug’s therapeutic actions are in the liver, bile, and gut lumen. Lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates. Although liver injury has not been associated with ursodiol therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated.
The treatment of antibiotics causing liver derangement with Ursodeoxycholic acid (PO) may be beneficial due to its therapeutic actions in the liver. However, liver injury is a potential concern with the formation of lithocholic acid, a toxic compound that can cause cholestatic liver injury. Since Ursodiol has not been directly associated with liver injury, it may be considered as a potential treatment option for liver derangement caused by antibiotics, but caution should be exercised and patients should be monitored for any signs of liver injury 2.
- Key considerations:
- Therapeutic actions in the liver
- Potential for liver injury with lithocholic acid formation
- Monitoring for liver injury is necessary
- Ursodiol may be a potential treatment option for liver derangement caused by antibiotics.
From the Research
Treatment of Antibiotics Causing Liver Derangement
- The treatment of antibiotics causing liver derangement is crucial to prevent severe consequences, including liver failure and death 3, 4.
- In cases of suspected drug-induced liver injury (DILI) related to antibiotics, prompt cessation of therapy is essential to prevent further liver damage 4.
- The severity of antibiotic-induced DILI varies widely, and the pattern is strongly influenced by age 3.
- In some cases, antibiotic-induced DILI can lead to chronic injury and vanishing bile duct syndrome 4.
- For patients with jaundice, there is approximately a 10% risk of death from liver failure and/or require liver transplantation 4.
Management of Acute Liver Failure
- Acute liver failure (ALF) is a severe, potentially reversible form of liver insufficiency, which is defined by the occurrence of hepatic coagulopathy and hepatic encephalopathy in patients with no previous hepatic disease 5.
- Initial diagnostics should include a detailed medical history, clinical examination, laboratory diagnostics, and abdominal sonography 5.
- The course of acute liver failure is very difficult to predict, so all patients with severe acute liver damage should be evaluated for transfer to a center 5.
- In progressive cases, liver transplantation is often the only life-saving measure 5.