Quinolones and fluoroquinolones are a type of antibiotics used to treat various infections. Although these drug work well, their use has also been linked to rare, but serious side effects, such as inflammations and ruptures of tendons or weakening of the wall of large arteries. Because of these side effects, the European Medicines Agency (EMA) issued new regulatory interventions targeting these drugs in 2018 and again in 2020. The goal of these interventions was to increase awareness of these side effects among doctors and to improve prescribing practices of antibiotics. Interventions included the sending of letters to doctors to warn against these side effects and changing the range of infections for with they drugs could be prescribed.The primary aim of this study is to study whether these interventions have resulted in different numbers of patients getting prescribed (fluoro)quinolones before and after these interventions and if the number of these serious side effects has decreased since they were put in place.
A population-based longitudinal observational study will be conducted using data from the CPRD database to examine antibiotic prescription patterns and trends of health outcomes related to antibiotic use. The study population will consist of all patients registered with the CPRD database during the study period who will be followed up until death, end of follow-up or end of registration. The population of interest will be selected based on recorded antibiotic prescription or recorded diagnosis of bacterial infection. The selected health ourcomes will be selected from both CPRD GOLD and Hospital Episode Statistics (HES) admission data. The outcomes of interest will be changes in prescribing patterns of fluoroquinolones and other systemic antibiotics, and changes in trends of selected health outcomes related to fluoroquinolone use (aortic dissection, aortic aneurysm, tendinitis, tendon rupure) or other antibiotics (hospitalization due to infection, allergy to antibiotics, clostridium difficile infection). We will use interrupted time series regression to determine whether statistically significant changes in prescribing or health ourcomes were associated with regulatory interventions. The outcomes will be assessed based on patients risk profile (medical history of aortic dissection, aortic aneurysm, tendinitis, tendon rupure; concomitant use of glucocorticoids or statins). The primary goal of the study is to assess the impact of risk minimisation measures (RMMs) targeting fluoroquinolone-containing medicinal products, taking into account the possible unintended effects of RMMs.
To assess the impact of regulatory intervention, we will assess drug utilization patterns and trends of several health outcomes associated with the use of fluoroquinolones or alternative antibiotics. The following outcomes will be examined:
1. Drug use (incident and prevalent use rates of antibiotics)
2. Tendinitis
3. Tendon rupture;
4. Aortic aneurysm;
5. Aortic dissection;
6. Clostridium difficile infections;
7. Allergic reactions related to antibiotic use;
8. Subsequent hospitalisations for infectious diseases.
Health outcome trends will be assessed if health outcomes will be recorded in the medical records in the period within the antibiotic treatment episode or within 30 days after the end of that treatment episode.
Helga Gardarsdottir - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University
Satu Johanna Siiskonen - Collaborator - Utrecht University
Tomas Lasys - Collaborator - Utrecht University
Yared Santa Ana Tellez - Collaborator - Utrecht University
HES Admitted Patient Care