Recurrent drug-induced liver injury (DILI) with ciprofloxacin and amoxicillin/clavulanic

Key words: Drug-induced liver injury. Ciprofloxacin. Amoxicillin. Clavulanic. Hepatotoxicity.

Dear Editor,

Ciprofloxacin and amoxicillin/clavulanic are two widely used antibiotics due to their high efficacy and few side effects. We present the case of a patient who consecutively developed DILI due to ciprofloxacin and amoxicillin/clavulanic.

A 56-year-old woman with a right renal lithiasis was admitted to hospital to receive a double J catheter. One week later, the patient was diagnosed of urinary infection and ciprofloxacin was prescribed. At four days, she referred pruritus, dark urine and acholia and developed jaundice ten days later. An abdominal ultrasound examination showed a normal liver with normal biliary tract.

She had no history of alcohol intake and had not taken other drug except ciprofloxacin. Laboratory testing showed aspartate aminotransferase (AST) 271 IU/mL, alanine aminotransferase (ALT) 506, alkaline phosphatase (ALP) 455 IU/L, gamma-glutamyltranspeptidase (GGT) of 412 IU/L and total bilirubin 9.5 mg/dL, leukocyte count 12.3 x 10⁹ and eosinophilia (10%). Prothrombin index was 0.98. Other causes of liver injury were excluded; serological tests for hepatitis A, B, C and E; autoantibodies, antibodies anti-Coxiella and anti-HIV. Serum electrophoresis and iron studies were all normal. The episode was attributed to ciprofloxacin treatment and the CIOMS/RUCAM scale, yielded a score of 9 (highly probable).

Three months later, the patient required a double J-catheter replacement. Antibiotic prophylaxis with amoxicillin/clavulanic was started. She was re-admitted to our hospital nine days later with complaints of jaundice and darkening of urine. Laboratory testing revealed: AST/ALT 452/692 IU/mL, total bilirubin 8.5 mg/dL, ALP of 348 IU/dL, GGT 230IU/dL, eosinophilia 3.3 %. Prothrombin activity was normal. Other causes of liver injury were excluded and ultrasonographic examination showed a normal biliary tract. Pathology findings in liver biopsy were suggestive of toxic hepatitis and a diagnosis of drug induced liver injury (DILI) secondary to amoxicillin/clavulanic was made. Causality assessment using the CIOMS/RUCAM scale yielded a score of 11 (highly probable).

Discussion

Recurrent DILI caused by different chemical structures is very uncommon. Susceptibility to DILI is believed to be the consequence of the interplay of multiple factors, including those related to the structure of the drug, the patient's genetic background and the influence of underlying diseases and associated medications (1).

Ciprofloxacin is a highly effective drug for the treatment of several infectious diseases. Although it is relatively safe, it may induce adverse effects that are usually transient and mild to moderate in severity (2-5). Fluoroquinolone liver injury is rapid in onset and often has immunoallergic features, indicating a hypersensitivity reaction.

Amoxicillin/clavulanic liver injury is currently one of the most common causes of DILI (6-8). It is usually associated with a moderate and asymptomatic increase in serum aminotransferase activity in about 23% of patients, although hepatic dysfunction with jaundice occurs infrequently.

Two are the main reasons why a patient might develop DILI from two different drugs. One possibility is that the mechanism is immune-mediated and the drugs or metabolites may share sufficient similarity to provide immunological cross-sensitization; a second possibility is that the drugs share a common target and DILI is directly related to the pharmacological action of the drug (1). The case of DILI induced by structurally unrelated antibiotics (ciprofloxacin and amoxicillin/clavulanic) raises the possibility of the existence of a common mechanism of liver injury for both drugs. This situation was previously described with moxifloxacin and amoxicillin/clavulanic (1).

Acknowledgements

We are indebted to Raúl Anchade and Maribel Lucena for their help in the orientation of the case.

Luís Moreno¹, Jordi Sánchez-Delgado^2,3, Mercedes Vergara^2,3,
Meritxell Casas², Mireia Miquel^2,3 and Blai Dalmau^2
1 Internal Medicine Service. Corporació Sanitària Parc Taulí. Sabadell, Barcelona. Spain.
² Hepatology Unit, Department of Digestive Diseases. Corporació Sanitària Parc Taulí Sabadell.
Hospital Universitari. Universitat Autònoma de Barcelona. Barcelona, Spain. ]]> ³ Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd).
Instituto de Salud Carlos III. Madrid, Spain

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