Quantification of the risk of liver injury associated with flucloxacillin: A UK population-based cohort study

Kevin Wing; Krishnan Bhaskaran; Louise Pealing; Adrian Root; Liam Smeeth; Tjeerd P. van Staa; Olaf H. Klungel; Robert F. Reynolds; Ian Douglas

doi:10.1093/jac/dkx183

Quantification of the risk of liver injury associated with flucloxacillin: A UK population-based cohort study

Kevin Wing^*, Krishnan Bhaskaran, Louise Pealing, Adrian Root, Liam Smeeth, Tjeerd P. van Staa, Olaf H. Klungel, Robert F. Reynolds, Ian Douglas

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 1046699 people with a first prescription for flucloxacillin (861962) or oxytetracycline (184737). 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 laboratoryconfirmed liver injury was 8.47 per 100000 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 100000 (95% CI 26.85-54.77), while those aged > 70 receiving consecutive prescriptions had a risk of 110.57 per 100000 (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.

Original language	English
Pages (from-to)	2636-2646
Number of pages	11
Journal	Journal of Antimicrobial Chemotherapy
Volume	72
Issue number	9
Early online date	1 Jul 2017
DOIs	https://doi.org/10.1093/jac/dkx183
Publication status	Published - 2017

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10.1093/jac/dkx183

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@article{99b366e85986440f8bf426179acf037a,

title = "Quantification of the risk of liver injury associated with flucloxacillin: A UK population-based cohort study",

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 1046699 people with a first prescription for flucloxacillin (861962) or oxytetracycline (184737). 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 laboratoryconfirmed liver injury was 8.47 per 100000 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 100000 (95% CI 26.85-54.77), while those aged > 70 receiving consecutive prescriptions had a risk of 110.57 per 100000 (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.",

author = "Kevin Wing and Krishnan Bhaskaran and Louise Pealing and Adrian Root and Liam Smeeth and {van Staa}, {Tjeerd P.} and Klungel, {Olaf H.} and Reynolds, {Robert F.} and Ian Douglas",

year = "2017",

doi = "10.1093/jac/dkx183",

language = "English",

volume = "72",

pages = "2636--2646",

journal = "Journal of Antimicrobial Chemotherapy",

issn = "0305-7453",

publisher = "Oxford University Press",

number = "9",

}

TY - JOUR

T1 - Quantification of the risk of liver injury associated with flucloxacillin

T2 - A UK population-based cohort study

AU - Wing, Kevin

AU - Bhaskaran, Krishnan

AU - Pealing, Louise

AU - Root, Adrian

AU - Smeeth, Liam

AU - van Staa, Tjeerd P.

AU - Klungel, Olaf H.

AU - Reynolds, Robert F.

AU - Douglas, Ian

PY - 2017

Y1 - 2017

N2 - 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 1046699 people with a first prescription for flucloxacillin (861962) or oxytetracycline (184737). 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 laboratoryconfirmed liver injury was 8.47 per 100000 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 100000 (95% CI 26.85-54.77), while those aged > 70 receiving consecutive prescriptions had a risk of 110.57 per 100000 (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.

AB - 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 1046699 people with a first prescription for flucloxacillin (861962) or oxytetracycline (184737). 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 laboratoryconfirmed liver injury was 8.47 per 100000 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 100000 (95% CI 26.85-54.77), while those aged > 70 receiving consecutive prescriptions had a risk of 110.57 per 100000 (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.

U2 - 10.1093/jac/dkx183

DO - 10.1093/jac/dkx183

M3 - Article

C2 - 28859440

AN - SCOPUS:85044929835

SN - 0305-7453

VL - 72

SP - 2636

EP - 2646

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

IS - 9

ER -

Quantification of the risk of liver injury associated with flucloxacillin: A UK population-based cohort study

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