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@ARTICLE{Wicherski:276749,
author = {Wicherski, Julia and Peltner, Jonas and Becker, Cornelia
and Schüssel, Katrin and Brückner, Gabriela and
Schlotmann, Andreas and Schröder, Helmut and Kern, Winfried
V and Haenisch, Britta},
title = {{H}igh risk for life-threatening adverse events of
fluoroquinolones in young adults: a large {G}erman
population-based cohort study.},
journal = {BMC medicine},
volume = {23},
number = {1},
issn = {1741-7015},
address = {London},
publisher = {BioMed Central},
reportid = {DZNE-2025-00307},
pages = {76},
year = {2025},
abstract = {Fluoroquinolone antibiotics have a high potential for
serious adverse drug reactions, but real-world evidence in
European patient cohorts is lacking. Therefore, we aim to
examine the association between fluoroquinolone exposure and
potentially life-threatening adverse events stratified by
age and gender in Germany.We conducted an administrative
cohort study using the active comparator new user design
with a risk window up to 365 days between January 2013 and
December 2019. Population-based longitudinal data from one
of the largest German statutory health insurances were used.
Episodes of newly dispensed fluoroquinolones (ciprofloxacin,
levofloxacin, ofloxacin, moxifloxacin, norfloxacin, and
enoxacin) were compared to other antibiotics (amoxicillin,
amoxicillin clavulanic acid, azithromycin, cefuroxime,
cephalexin, clindamycin, sulfamethoxazole-trimethoprim, and
doxycycline). Endpoints were defined by incident diagnoses
of aortic aneurysm/dissection, cardiac arrhythmia,
hepatotoxicity, and all-cause mortality. Adjusted hazard
ratios were estimated from piece-wise exponential additive
mixed models with smooth non-linear effects for person-time
and age and adjusted for comorbidities, year and quarter at
index.The cohorts comprised 15,139,840; 11,760,159;
11,027,175; and 15,305,757 antibiotic episodes. Patients
during fluoroquinolone episodes were older (59 versus 51
years) and more often female $(58\%$ versus $54\%).$ We
counted 46,502; 446,727; 19,125; and 474,411 incident
endpoints. Relative risk for all-cause mortality and
hepatotoxicity was high for < 40-year- and 40-69-year-old
females (aHR = 1.77, $95\%$ CI 1.55-2.03 and aHR = 1.42,
$95\%$ CI 1.32-1.53), respectively. For aortic
aneurysm/dissection a nominally increased relative risk for
< 40-year-old females was found (aHR = 1.42, $95\%$ CI
0.96-2.11), although $95\%$ CI indicates that a small
relative risk reduction is also supported by the data.
Relative risk for cardiac arrhythmia was increased for men
aged < 40 years (aHR = 1.14, $95\%$ CI 1.08-1.20). High
relative risks for each endpoint were also identified
depending on choice of active comparator, and risks
increased with higher defined daily doses and shorter
follow-up.This study contributes real-world evidence to
endpoint-specific differences of risks in patient subgroups
which need to be considered to improve fluoroquinolone drug
safety.},
keywords = {Humans / Germany: epidemiology / Female / Male /
Fluoroquinolones: adverse effects / Adult / Middle Aged /
Anti-Bacterial Agents: adverse effects / Aged / Cohort
Studies / Young Adult / Arrhythmias, Cardiac: chemically
induced / Arrhythmias, Cardiac: epidemiology / Aortic
Dissection: epidemiology / Aortic Dissection: chemically
induced / Chemical and Drug Induced Liver Injury:
epidemiology / Chemical and Drug Induced Liver Injury:
etiology / Adolescent / Drug-Related Side Effects and
Adverse Reactions: epidemiology / Age Factors / Risk Factors
/ Adverse drug reactions (Other) / Antibiotics (Other) /
Cohort study (Other) / Fluoroquinolones (Other) / Real-world
evidence (Other) / Fluoroquinolones (NLM Chemicals) /
Anti-Bacterial Agents (NLM Chemicals)},
cin = {AG Hänisch},
ddc = {610},
cid = {I:(DE-2719)1013010},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39920723},
pmc = {pmc:PMC11806691},
doi = {10.1186/s12916-025-03919-0},
url = {https://pub.dzne.de/record/276749},
}