Antibiotic-Induced Liver Toxicity: Mechanisms, Clinical Features and Causality Assessment

Abstract

Antibiotics are the therapeutic agents most often associated with hepatotoxicity. However, this is mainly due to the widespread prescription of these drugs. The relative risk of antibiotic-related hepatotoxicity is low. Causality assessment of suspected drug-induced liver injury (DILI) related to antibiotics can be difficult, particularly because some cases occur long after the drug has been stopped. Among the penicillins, amoxicillin clavulanate is the most associated with hepatotoxicity and is the most frequent cause of DILI-related hospitalisations. Flucloxacillin ranks as the second highest cause of DILI in many countries. The severity of antibiotic-induced DILI varies widely, with the hepatitis-like (hepatocellular) damage tending to be more severe that than cholestatic/mixed type. The pattern is strongly influenced by age. Recently telithromycin (a new generation macrolide) has been linked with DILI, with a typical pattern, which includes abrupt commencement of fever, abdominal pain, jaundice and, in some cases, ascites. Antibiotic-induced DILI appears, in most instances, to be idiosyncratic. Genetic-association studies have recently identified genotypes related to flucloxacillin and possibly to amoxicillin-clavulanate hepatotoxicity.

Severe Drug-Induced Liver Injury as an Adverse Drug Event of Antibiotics: A Case Report and Review of the Literature

“…A recent review details the hepatic damage caused by amoxicillin without clavulanic acid as a hepatocellular pattern [13], whereas there are a few case reports which describe the cholestatic pattern of liver damage by amoxicillin [14,15]. One case report describes the development of a vanishing bile duct syndrome associated with amoxicillin therapy.…”

“…1) was introduced in the 1990s. It is recognized to be the best evaluation system currently in use to establish a causal relationship between a potentially liver-toxic drug and liver damage [13,32]. It involves a scoring system which categorizes the suspicion into “definite or highly probable” (score >8), “probable” (score 6-8), “possible” (score 3-5), “unlikely” (score 1-2), and “excluded” (score ≤0) [33,34].…”

Infections in Alcoholic Liver Disease

“…Drug-induced liver injury can range from asymptomatic transient liver enzyme elevations to fulminant liver failure. 76 Most commonly, patients develop hepatitis, which can also be termed hepatocellular or cytotoxic injury. Commonly used antimicrobials that have been associated with hepatic injury are noted in Table 3.…”

Hepatitis colestásica aguda asociada a levofloxacino

“…Las quinolonas son un grupo de antibióticos que pueden causar elevaciones transitorias de las enzimas hepáticas, pero parecen tener un menor potencial hepatotóxico que otros antibióticos, como beta-lactámicos o sulfamidas 1,2 .…”

“…Representa en torno al 0,5% de casos nuevos de TB y el 11% de las formas extrapulmonares 1 . Puede afectar a cualquier tramo del tracto digestivo, siendo el más frecuente la región ileocecal [1][2][3][4] .…”