Quantification of the Risk of Liver Injury Associated with Flucloxacillin: a UK Population-based Cohort Study

Overview

Journal J Antimicrob Chemother

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2017 Sep 2

PMID 28859440

Citations 10

Authors

Kevin Wing

Krishnan Bhaskaran

Louise Pealing

Adrian Root

Liam Smeeth

Tjeerd P van Staa

Olaf H Klungel

Robert F Reynolds

Ian Douglas

Affiliations

Soon will be listed here.

Abstract

Background: Flucloxacillin is an established cause of liver injury. Despite this, there are a lack of published data on both the strength of association after adjusting for potential confounders, and the absolute incidence among different subgroups of patients.

Objectives: To assess the relative and absolute risks of liver injury following exposure to flucloxacillin and identify subgroups at potentially increased risk.

Methods: A cohort study between 1 January 2000 and 1 January 2012 using the UK Clinical Practice Research Datalink, including 1 046 699 people with a first prescription for flucloxacillin (861 962) or oxytetracycline (184 737). Absolute risks of experiencing both symptom-defined (jaundice) and laboratory-confirmed liver injury within 1-45 and 46-90 days of antibiotic initiation were estimated. Multivariable logistic regression was used to estimate 1-45 day relative effects.

Results: There were 183 symptom-defined cases (160 prescribed flucloxacillin) and 108 laboratory-confirmed cases (102 flucloxacillin). The 1-45 day adjusted risk ratio for laboratory-confirmed injury was 5.22 (95% CI 1.64-16.62) comparing flucloxacillin with oxytetracycline use. The 1-45 day risk of laboratory-confirmed liver injury was 8.47 per 100 000 people prescribed flucloxacillin (95% CI 6.64-10.65). People who received consecutive flucloxacillin prescriptions had a 1-45 day risk of jaundice of 39.00 per 100 000 (95% CI 26.85-54.77), while those aged >70 receiving consecutive prescriptions had a risk of 110.57 per 100 000 (95% CI 70.86-164.48).

Conclusions: The short-term risk of laboratory-confirmed liver injury was >5-fold higher after a flucloxacillin prescription than an oxytetracycline prescription. The risk of flucloxacillin-induced liver injury is particularly high within those aged >70 and those who receive multiple flucloxacillin prescriptions. The stratified risk estimates from this study could help guide clinical care.

Citing Articles

Genetic and Genomic Approaches to the Study of Drug-Induced Liver Injury.

Daly A Liver Int. 2024; 45(1):e16191.

PMID: 39704445 PMC: 11660537. DOI: 10.1111/liv.16191.

Idiosyncratic Hepatocellular Drug-Induced Liver Injury by Flucloxacillin with Evidence Based on Roussel Uclaf Causality Assessment Method and HLA B*57:01 Genotype: From Metabolic CYP 3A4/3A7 to Immune Mechanisms.

Teschke R Biomedicines. 2024; 12(10).

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Genetic Variations and Antibiotic-Related Adverse Events.

Principi N, Petropulacos K, Esposito S Pharmaceuticals (Basel). 2024; 17(3).

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Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet.

Lucena M, Villanueva-Paz M, Alvarez-Alvarez I, Aithal G, Bjornsson E, Cakan-Akdogan G Pharmacol Res. 2023; 200:107046.

PMID: 38159783 PMC: 7617395. DOI: 10.1016/j.phrs.2023.107046.

Development of mouse models with restricted HLA-B∗57:01 presentation for the study of flucloxacillin-driven T-cell activation and tolerance in liver injury.

Ananthula S, Krishnaveni Sivakumar K, Cardone M, Su S, Roderiquez G, Abuzeineh H J Allergy Clin Immunol. 2023; 152(2):486-499.e7.

PMID: 37030592 PMC: 10524621. DOI: 10.1016/j.jaci.2023.03.029.

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