The Frequency of Drug-Induced Liver Injury Due to Antibiotics Among Hospitalised Patients.

IF 4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Safety Pub Date : 2025-03-12 DOI:10.1007/s40264-025-01541-w

Robert A Björnsson, Sigurdur Sölvi Sigurdsson, Dagur Tjörvi Arnarson, Egill Logason, Einar Stefan Björnsson

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Abstract

Introduction: Most epidemiological studies have found antibiotics to be the most common cause of drug-induced liver injury (DILI). It is unclear what the risk of DILI is associated with different antibiotics.

Objective: The aim of the study was to assess the frequency of DILI due to the most commonly used antibiotics among inpatients, in a population-based setting.

Methods: Patients who were treated with the 14 most-used antibiotics at Landspitali University Hospital Iceland 2012-2023, with concomitant: > 5 × upper limit of normal (ULN) of alanine aminotransferase (ALT) and/or > 2 × ULN of alkaline phosphatase (ALP), were identified. If DILI was a potential cause, the Revised Electronic Causality Assessment Method (RECAM) method was used to determine likelihood of DILI.

Results: Overall 2292 patients fulfilled the inclusion criteria, 52 of whom were found to have DILI, median age 67 (range 21-93) years, 58% females, 17 (33%) with jaundice and three (5.8%) died of liver failure. The most commonly implicated agent was amoxicillin/clavulanate (n = 23) in 1:1327 users (0.075%), ceftriaxone (n = 8) 1:3779 (0.02%), cefazolin (n = 7) 1: 6363 (0.016%), cloxacillin 1:6024 (n = 4) (0.017%), piperacillin/tazobactam (n = 2) 1:1551 (0.097%), vancomycin (n = 2) 1:1966 (0.076%), trimethoprim-sulfamethoxazole (TMP/SMX) (n = 3) 1:1096 (0.091%) and ciprofloxacin (n = 1) 1:10,938 (0.009%). In two cases, more than one antibiotic was considered likely.

Conclusions: Drug-induced liver injury was found to be a rare adverse effect of antibiotics in a population-based setting. Overall, 33% presented with jaundice but three died of liver failure, all due to amoxicillin/clavulanate, which was the most common cause occurring in around 1 in 1300 users. However, TMP/SMX was associated with the highest proportional risk of DILI.

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导言：大多数流行病学研究发现，抗生素是导致药物性肝损伤（DILI）的最常见原因。目前尚不清楚不同抗生素引起药物性肝损伤的风险有多大：本研究旨在以人群为基础，评估住院患者中最常用抗生素导致药物性肝损伤的频率：方法：2012-2023 年期间在冰岛兰茨皮塔利大学医院接受过 14 种最常用抗生素治疗的患者，同时伴有以下情况者：丙氨酸氨基转移酶 (ALT) > 5 倍正常值上限 (ULN) 和/或碱性磷酸酶 (ALP) > 2 倍正常值上限的患者。如果DILI是一个潜在原因，则采用修订的电子因果关系评估方法（RECAM）来确定DILI的可能性：共有 2292 名患者符合纳入标准，其中 52 人被发现患有 DILI，中位年龄为 67 岁（21-93 岁），58% 为女性，17 人（33%）出现黄疸，3 人（5.8%）死于肝衰竭。最常见的药物是阿莫西林/克拉维酸（23 人），使用比例为 1:1327（0.075%）；头孢曲松（8 人），使用比例为 1:3779（0.02%）；头孢唑啉（7 人），使用比例为 1:6363（0.016%）；氯唑西林，使用比例为 1:6024（4 人）（0.017%）、哌拉西林/他唑巴坦（n = 2）1:1551（0.097%）、万古霉素（n = 2）1:1966（0.076%）、三甲双胍-磺胺甲噁唑（TMP/SMX）（n = 3）1:1096（0.091%）和环丙沙星（n = 1）1:10938（0.009%）。有两个病例可能使用了一种以上的抗生素：结论：在以人群为基础的研究中发现，药物引起的肝损伤是抗生素的一种罕见不良反应。总体而言，33%的人出现黄疸，但有三人死于肝功能衰竭，全部都是阿莫西林/克拉维酸引起的，这是最常见的原因，大约每1300名使用者中就有一人死于肝功能衰竭。不过，TMP/SMX 与 DILI 的最高比例风险相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Safety 医学-毒理学

CiteScore

7.60

自引率

7.10%

发文量

112

审稿时长

6-12 weeks

期刊介绍： Drug Safety is the official journal of the International Society of Pharmacovigilance. The journal includes: Overviews of contentious or emerging issues. Comprehensive narrative reviews that provide an authoritative source of information on epidemiology, clinical features, prevention and management of adverse effects of individual drugs and drug classes. In-depth benefit-risk assessment of adverse effect and efficacy data for a drug in a defined therapeutic area. Systematic reviews (with or without meta-analyses) that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. Original research articles reporting the results of well-designed studies in disciplines such as pharmacoepidemiology, pharmacovigilance, pharmacology and toxicology, and pharmacogenomics. Editorials and commentaries on topical issues. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Drug Safety Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.