The risk of drug-induced liver injury associated with flucloxacillin : a nationwide, entropy-balanced cohort study
Nibell, Olof LU ; Björk, Jonas LU
; Nilsson, Anton
LU
; Jacobsson, Gunnar
and Inghammar, Malin
LU
(2025)
In Clinical Microbiology and Infection
31(4).
p.600-606
- Abstract
Objectives: In this nationwide cohort study in a Scandinavian setting, we aimed to investigate the magnitude of association between flucloxacillin use and drug-induced liver injury (DILI). Methods: Nationwide cohort study among adults in Sweden, 2006–2018, was conducted. Register data on filled prescriptions, patient characteristics, co-medications, and DILI were linked. All filled prescriptions for flucloxacillin and oral clindamycin, among Swedish adults aged 18–85 years, were identified. Entropy-balancing methods were used to control for confounding. Cox regression was used to estimate hazard ratios (HRs) for a first diagnosis of DILI, defined as admission to hospital, emergency department or specialist care, or death because of... (More)
Objectives: In this nationwide cohort study in a Scandinavian setting, we aimed to investigate the magnitude of association between flucloxacillin use and drug-induced liver injury (DILI). Methods: Nationwide cohort study among adults in Sweden, 2006–2018, was conducted. Register data on filled prescriptions, patient characteristics, co-medications, and DILI were linked. All filled prescriptions for flucloxacillin and oral clindamycin, among Swedish adults aged 18–85 years, were identified. Entropy-balancing methods were used to control for confounding. Cox regression was used to estimate hazard ratios (HRs) for a first diagnosis of DILI, defined as admission to hospital, emergency department or specialist care, or death because of DILI, within 45 days from the start of treatment. Results: Within the main 45-day risk period, there were 219 events of DILI among 1 443 622 flucloxacillin users (incidence rate: 14/10 000 person-years) as compared with nine events among 583 847 oral clindamycin group (incidence rate: 1.4/10 000 person-years). This corresponded to an HR of 7.32 (95% CI: 4.1–13.0). The absolute risk difference for users of flucloxacillin compared with clindamycin in the main period was 11 cases of DILI (95% CI: 5–20) per 100 000 courses. The risk diminished in the subsequent periods, 46–90 days (HR: 4.17; 95% CI: 1.44–12.10), and 91–180 days (HR: 0.72; 95% CI: 0.36–1.44). Discussion: In this nationwide cohort study, the use of flucloxacillin was associated with a sevenfold increased risk of DILI, predominantly in the first 45 days of exposure.
(Less)
- author
- Nibell, Olof
LU
; Björk, Jonas
LU
; Nilsson, Anton
LU
; Jacobsson, Gunnar
and Inghammar, Malin
LU
- organization
- publishing date
- 2025-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Acute liver injury, Antimicrobial safety, DILI, Epidemiology, Flucloxacillin
- in
- Clinical Microbiology and Infection
- volume
- 31
- issue
- 4
- pages
- 7 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:39716553
- scopus:85215960533
- ISSN
- 1198-743X
- DOI
- 10.1016/j.cmi.2024.12.013
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2025 The Authors
- id
- 12b11c48-fdaa-47c2-a4f2-01d6c0de2b5d
- date added to LUP
- 2025-04-10 09:51:45
- date last changed
- 2025-04-11 02:16:00
@article{12b11c48-fdaa-47c2-a4f2-01d6c0de2b5d,
abstract = {{<p>Objectives: In this nationwide cohort study in a Scandinavian setting, we aimed to investigate the magnitude of association between flucloxacillin use and drug-induced liver injury (DILI). Methods: Nationwide cohort study among adults in Sweden, 2006–2018, was conducted. Register data on filled prescriptions, patient characteristics, co-medications, and DILI were linked. All filled prescriptions for flucloxacillin and oral clindamycin, among Swedish adults aged 18–85 years, were identified. Entropy-balancing methods were used to control for confounding. Cox regression was used to estimate hazard ratios (HRs) for a first diagnosis of DILI, defined as admission to hospital, emergency department or specialist care, or death because of DILI, within 45 days from the start of treatment. Results: Within the main 45-day risk period, there were 219 events of DILI among 1 443 622 flucloxacillin users (incidence rate: 14/10 000 person-years) as compared with nine events among 583 847 oral clindamycin group (incidence rate: 1.4/10 000 person-years). This corresponded to an HR of 7.32 (95% CI: 4.1–13.0). The absolute risk difference for users of flucloxacillin compared with clindamycin in the main period was 11 cases of DILI (95% CI: 5–20) per 100 000 courses. The risk diminished in the subsequent periods, 46–90 days (HR: 4.17; 95% CI: 1.44–12.10), and 91–180 days (HR: 0.72; 95% CI: 0.36–1.44). Discussion: In this nationwide cohort study, the use of flucloxacillin was associated with a sevenfold increased risk of DILI, predominantly in the first 45 days of exposure.</p>}},
author = {{Nibell, Olof and Björk, Jonas and Nilsson, Anton and Jacobsson, Gunnar and Inghammar, Malin}},
issn = {{1198-743X}},
keywords = {{Acute liver injury; Antimicrobial safety; DILI; Epidemiology; Flucloxacillin}},
language = {{eng}},
number = {{4}},
pages = {{600--606}},
publisher = {{Wiley-Blackwell}},
series = {{Clinical Microbiology and Infection}},
title = {{The risk of drug-induced liver injury associated with flucloxacillin : a nationwide, entropy-balanced cohort study}},
url = {{http://dx.doi.org/10.1016/j.cmi.2024.12.013}},
doi = {{10.1016/j.cmi.2024.12.013}},
volume = {{31}},
year = {{2025}},
}