Acute Liver Failure Due To Amoxicillin and Amoxicillin/Clavulanate

Abstract

The aim of our study is to report upon the presentation of two patients with life-threatening acute liver failure (ALF) due to amoxicillin and amoxicillin/clavulanate. A 59-year-old, Caucasian male presented with ALF 34 days after receiving amoxicillin/clavulanate. Despite aggressive supportive care, he died on hospital day 10. A 42-year-old, Caucasian female presented with ALF 21 days after receiving amoxicillin. She underwent successful liver transplantation on hospital day 19. In both cases, all competing causes of ALF had been excluded, liver pathology was consistent with drug-induced hepatitis, and cases were deemed "definite/highly probable" using causality assessment. Amongst 14 prior ALF/death cases due to amoxicillin/clavulanate, the mean age (62 years), male predominance (57%), and mean delay from drug cessation to presentation (17 days) is similar to what has been reported in patients with self-limited cholestatic hepatitis. Acute liver failure is a rare manifestation of amoxicillin and amoxicillin/clavulanate hepatotoxicity with no obvious clinical features at presentation portending a poor prognosis. Early transfer of patients with severe drug-induced hepatotoxicity (i.e., encephalopathy or coagulopathy) to a transplant center is recommended due to their poor likelihood of recovery.

Drug-Induced Liver Injury

“…71,74,77 Most patients recover within 4 to 6 months following DILI due to amoxicillin-clavulanate. 66,71,76 Rare patients may progress to ductopenia or to acute liver failure and death 77,78 ; severe outcomes were reported in 2.9% of cases in one series. 20 Because amoxicillin-clavulanate hepatotoxicity may cause decompensation of cirrhosis, it should be administered with caution in cirrhotic patients, especially those who are elderly or have had previous exposure to the drug.…”

Drug-induced liver injury: an overview over the most critical compounds

“…Risk factors for hepatotoxicity are age over 65 years, female sex and repeated course of the antibiotic (García Rodríguez et al 1996;Lucena et al 2006). Most cases are mild to moderate in severity, but protracted course has also been observed where patients have experienced months of jaundice and can, in rare cases, lead to acute liver failure or require transplantation (Fontana et al 2005). Flucloxacillin is the most common reason of idiosyncratic liver injury in Sweden, with 16 % of all DILI cases (Björnsson and Olsson 2005).…”

Hepatotoxicity of Antibacterials: Pathomechanisms and Clinical Data

“…The general risk of transplantation or death was 11.7% in this population [18]. Acute liver failure due to amoxicillin/ clavulanate is most commonly caused by cholestatic hepatitis and affects men more frequently [61]. A retrospective analysis of 153 amoxicillin/clavulanate-related cases of DILI showed a predominance of the mixed type (n = 83) rather than the hepatocellular (n = 35) or cholestatic (n = 24) types [62].…”