A Case of Drug-Induced Cholangitis and Cholestasis From Amoxicillin/Clavulanic Acid and Levofloxacin

Abstract

Introduction: Drug-induced liver injury (DILI) continues to be an important disease in clinical practice. Amoxicillin/clavulanic acid and levofloxacin are commonly used with a good safety profile. We describe a case of drug-induced cholangitis and cholestasis from amoxicillin/clavulanic acid and levofloxacin. Case Report: An 89-year-old male presented with a 1-day history of jaundice, dark urine, and pale stools. He was treated with 2 10-day courses of amoxicillin/clavulanic acid for a urinary tract infection, followed by a 10-day course of levofloxacin for pneumonia 1 week before presentation. He does not drink alcohol and had no personal or family history of liver disease. Physical exam was significant for jaundice. Laboratory evaluation demonstrated a total bilirubin of 11.1 mg/dL, direct bilirubin of 9.1 mg/dL, alkaline phosphatase of 1001 U/L, gamma-glutamyl-transpeptidase of 793 U/L, alanine aminotransferase (ALT) of 343 U/L, aspartate aminotransferase (AST) of 427 U/L, INR of 1.03, and albumin of 3.3 g/dL. Magnetic resonance cholangiopancreatography (MRCP) was negative for extrahepatic and intrahepatic biliary dilation. A liver biopsy revealed inflammation infiltrating the bile ducts and hepatocanalicular cholestasis consistent with drug-induced cholangitis and cholestasis. His liver function tests started to improve gradually within days after stopping levofloxacin. Discussion: DILI continues to be an important disease in clinical practice. Its diagnosis is mainly based on the exclusion of alternative causes of liver damage. Amoxicillin/clavulanic acid is a combination of amoxicillin and the β-lactamase inhibitor clavulanic acid. The latter component seems to be the prime offender for the liver injury. Amoxicillin/clavulanic acid has been reported to cause drug-induced intrahepatic cholestasis due to a metabolic idiosyncrasy or a hypersensitivity mechanism. It has also been reported to cause ductopenia. Levofloxacin is a fluoroquinolone commonly used to treat respiratory infections. Fluoroquinolones have been associated with drug-induced liver injury, ranging from a brief rise in transaminase level or cholestatic jaundice to severe hepatotoxicity. Levofloxacin has been associated with acute hepatitis, fulminant hepatic failure, and death. The mechanism of levofloxacin-induced hepatotoxicity is not known. Treatment for DILI is mainly the cessation of the offending drug, which may lead to recovery in liver enzyme abnormalities. We believe that our patient suffered from amoxicillin/clavulanic acid and levofloxacin-induced cholestasis and cholangitis. Clinicians should be familiar with the potential hepatoxicities from amoxicillin/clavulanic acid and levofloxacin.