Meropenem Can Cause Jaundice Through Drug-Induced Liver Injury
Yes, meropenem can cause jaundice, though it is rare. This occurs through drug-induced liver injury (DILI) with mixed hepatocellular and cholestatic patterns, and in severe cases can lead to vanishing bile duct syndrome (VBDS).
Mechanism and Clinical Presentation
Meropenem-induced liver injury typically manifests as:
- Mixed hepatocellular and cholestatic injury with jaundice and pruritus developing within 3 days to 3 weeks after starting therapy 1, 2
- Vanishing bile duct syndrome (VBDS) in severe cases, characterized by progressive destruction and disappearance of small intrahepatic bile ducts with resultant cholestasis 1, 3
- Rapid onset with liver enzyme elevations appearing as early as 48 hours after administration, reaching maximum levels at 5 days 4
Risk Factors and Monitoring
Patients with pre-existing liver disease are at substantially higher risk for severe, potentially life-threatening DILI when exposed to any hepatotoxic medication 5. For meropenem specifically:
- Pre-existing advanced liver disease increases the likelihood of drug-induced hepatitis 5
- Abnormal baseline aminotransferases alone are an independent risk factor for DILI 5
- Patients with marginal hepatic reserve may experience severe, even life-threatening superimposed DILI 5
Monitor liver function tests (ALT, AST, alkaline phosphatase, total bilirubin) every 1-4 weeks for at least the first 2-3 months when using potentially hepatotoxic medications in patients with liver disease 5.
Diagnostic Approach
When jaundice develops in a patient receiving meropenem:
- Obtain hepatic profile with fractionated bilirubin (conjugated vs. unconjugated), alkaline phosphatase, ALT, AST, and complete blood count 6
- Perform abdominal ultrasound as first-line imaging to exclude biliary obstruction 6
- Rule out other causes including infectious and immunologic conditions before attributing to drug effect 1
- Consider liver biopsy if cholestasis persists despite drug discontinuation to confirm VBDS (demonstrates absence of bile ducts) 1, 3
Management
Discontinue meropenem immediately when drug-induced liver injury is suspected 1, 2, 3, 4. Key management principles:
- Do not rechallenge with meropenem if liver injury has occurred, as re-exposure causes immediate recurrence of elevated bilirubin and liver enzymes 3, 4
- Switch to alternative antibiotics based on culture sensitivities (e.g., ciprofloxacin, fluoroquinolones) 3
- Expect gradual improvement with liver function tests normalizing over several weeks to months after discontinuation 1, 2, 3
Clinical Pitfalls
- High index of suspicion is necessary as VBDS and other forms of DILI are easily missed 1
- Antibiotics are the most common drug class causing DILI across all major studies, with approximately 10% risk of death from liver failure or need for transplantation in patients who develop jaundice 7
- Delayed recognition is dangerous - early identification and prompt cessation of therapy is critical to prevent progression to acute liver failure 7, 4