Can cefepime (a fourth-generation cephalosporin antibiotic) cause elevations in liver transaminases, particularly in patients with a history of liver disease or psychiatric conditions such as schizophrenia or bipolar disorder?

Cefepime and Transaminase Elevations

Yes, cefepime can cause elevations in liver transaminases, though this is a rare adverse effect that requires clinical vigilance, particularly when other common causes have been excluded.

Evidence for Hepatotoxicity

Cefepime-induced liver injury is documented in case reports, though it remains an uncommon complication:

• A 2023 case report demonstrated mixed liver injury with ALT rising from 22 U/L to 210 U/L and AST from 44 U/L to 239 U/L by day 4 of cefepime therapy, with normalization after discontinuation (Roussel Uclaf Causality Assessment Method score of 7, indicating "possible" causality) 1

• A 2019 case documented cholestatic hepatitis in a 93-year-old patient with elevated transaminases and direct bilirubin after cefepime administration, with complete recovery upon drug cessation (RUCAM score of 7) 2

• The temporal relationship is key: liver enzyme elevations typically begin within 2-4 days of treatment initiation and normalize within days to weeks after discontinuation 1, 2

Clinical Monitoring Approach

When to suspect cefepime-induced liver injury:

• Monitor baseline liver function tests before initiating therapy in high-risk patients (those with pre-existing liver disease, advanced age, or critical illness) 1, 2

• If transaminases rise during cefepime therapy, particularly ALT/AST >3× upper limit of normal, consider cefepime as a potential cause after excluding more common etiologies 1

• Rule out alternative causes systematically: viral hepatitis, sepsis-related hypoperfusion, other hepatotoxic medications, biliary obstruction, and ischemic hepatitis 1, 2

High-Risk Populations Requiring Extra Vigilance

Patients with psychiatric conditions and liver disease warrant special attention:

• Patients with schizophrenia or bipolar disorder on psychotropic medications may already have baseline transaminase elevations from neuroleptics or mood stabilizers, complicating the clinical picture 3, 4

• Metabolic syndrome and non-alcoholic steatohepatitis (NASH) are frequent in patients with chronic psychiatric disorders on psychotropic drugs, creating a confounding baseline 4

• Patients with cirrhosis have additional risk for cefepime complications, including both hepatotoxicity and encephalopathy due to blood-brain barrier dysfunction 5

Management Algorithm

If transaminases elevate during cefepime therapy:

1. Immediately assess the degree of elevation: ALT/AST >3× ULN requires prompt action 1

2. Exclude alternative causes: Check for sepsis progression, hypotension, viral hepatitis serologies, other hepatotoxic drugs, and imaging for biliary pathology 1, 2

3. Discontinue cefepime if no alternative cause identified and liver injury is moderate to severe, switching to an alternative antibiotic with different hepatic profile 1, 2

4. Monitor liver enzymes every 1-2 weeks after discontinuation until normalization 1, 2

5. Document as drug-induced liver injury and avoid rechallenge with cefepime 1, 2

Critical Pitfalls to Avoid

• Do not attribute all transaminase elevations to sepsis alone without considering drug-induced causes, especially when clinical improvement occurs but liver enzymes worsen 1

• Do not overlook cefepime as a cause simply because hepatotoxicity is rare; the temporal relationship and lack of alternative explanations are diagnostic 1, 2

• In patients with psychiatric disorders, do not assume elevated transaminases are solely from psychotropic medications without evaluating recent antibiotic additions 4

• Renal dysfunction increases risk not only for cefepime neurotoxicity but may also contribute to hepatotoxicity through drug accumulation 5