High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study
Abstract Background 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 stra...
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2025-02-01
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| author | Julia Wicherski Jonas Peltner Cornelia Becker Katrin Schüssel Gabriela Brückner Andreas Schlotmann Helmut Schröder Winfried V. Kern Britta Haenisch |
| author_facet | Julia Wicherski Jonas Peltner Cornelia Becker Katrin Schüssel Gabriela Brückner Andreas Schlotmann Helmut Schröder Winfried V. Kern Britta Haenisch |
| author_sort | Julia Wicherski |
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| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-60b867d31bdb4e20b4784401dda7267c2025-02-09T12:40:53ZengBMCBMC Medicine1741-70152025-02-0123111310.1186/s12916-025-03919-0High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort studyJulia Wicherski0Jonas Peltner1Cornelia Becker2Katrin Schüssel3Gabriela Brückner4Andreas Schlotmann5Helmut Schröder6Winfried V. Kern7Britta Haenisch8Federal Institute for Drugs and Medical Devices (BfArM), PharmacoepidemiologyGerman Centre for Neurodegenerative Diseases (DZNE), Pharmacoepidemiology in Neurodegenerative DisordersFederal Institute for Drugs and Medical Devices (BfArM), PharmacoepidemiologyResearch Institute of AOK (WIdO)Research Institute of AOK (WIdO)Research Institute of AOK (WIdO)Research Institute of AOK (WIdO)Division of Infectious Diseases, Department of Medicine II, Faculty of Medicine and Medical Centre, University of FreiburgFederal Institute for Drugs and Medical Devices (BfArM), PharmacoepidemiologyAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12916-025-03919-0FluoroquinolonesAntibioticsAdverse drug reactionsReal-world evidenceCohort study |
| spellingShingle | Julia Wicherski Jonas Peltner Cornelia Becker Katrin Schüssel Gabriela Brückner Andreas Schlotmann Helmut Schröder Winfried V. Kern Britta Haenisch High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study BMC Medicine Fluoroquinolones Antibiotics Adverse drug reactions Real-world evidence Cohort study |
| title | High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study |
| title_full | High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study |
| title_fullStr | High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study |
| title_full_unstemmed | High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study |
| title_short | High risk for life-threatening adverse events of fluoroquinolones in young adults: a large German population-based cohort study |
| title_sort | high risk for life threatening adverse events of fluoroquinolones in young adults a large german population based cohort study |
| topic | Fluoroquinolones Antibiotics Adverse drug reactions Real-world evidence Cohort study |
| url | https://doi.org/10.1186/s12916-025-03919-0 |
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