The cumulative incidence of seizures during 21 days after new use of oral antibiotics - a cohort study

Date of ISAC Approval: 
Lay Summary: 
Use of antibiotics, drugs to cure bacterial infections, has repeatedly been associated with the occurrence of epileptic seizures (abnormal activity in the brain affecting a person's behavior, consciousness or appearance). Various types of antibiotics have been associated with different risks of epileptic seizures. Generally, the risk of epileptic seizure seems to be highest when high doses of antibiotics are used (for example in hospital), or when patients have impaired kidney function, brain disorders, fever, brain infections, or infections in which bacteria are distributed throughout the body. However, it is not clear whether antibiotics are associated with an increased risk of epileptic seizures when taken at usual outpatient (prescribed by the general practitioner) doses. The goal of this study is to quantify the risk of new-onset epileptic seizures in children and adult patients who are newly prescribed oral (taken by mouth) antibiotics by a general practitioner. We further plan to investigate the potential roles of the type of antibiotic, the antibiotic dose, the patients' age, kidney function, underlying type of infection, and pre-existing drug dependence, metabolic disturbances, or brain disorders.
Technical Summary: 
We will estimate the cumulative incidence of epileptic seizures in patients aged 1 year or older during the 21-day period after recording of a new oral antibiotic prescription (beta-lactam antibiotics, quinolones, macrolides/lincosamides, tetracyclines, or sulfonamides/ trimethoprim) in the patient record. We will assess the cumulative incidence of epileptic seizures in a matched comparison group of patients not prescribed antibiotics. We will divide the study period (January 1, 1997 and December 31, 2016) into twenty 1-year study blocks, and each patient who was exposed in a block will be matched 1:1 to a patient who was unexposed within the same block on general practice, age, sex, calendar time, and recorded history on the database. We will estimate cumulative incidences of epileptic seizures stratified by age, estimated glomerular filtration rate, underlying type of infection, body mass index, alcohol consumption, smoking status, drug dependence, metabolic disorders, brain disorders, and prescribed antibiotic type and dose. We will also calculate risk ratios of epileptic seizures by dividing the cumulative incidence in exposed patients by the cumulative incidence in the matched non-exposed comparison group.
Health Outcomes to be Measured: 
- Incident seizures

Dr Susan S Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Bojana Vulin - Collaborator - University of Basel
Charlotte Holze - Collaborator - University of Basel
Christoph Meier - Collaborator - University of Basel
Dr Cornelia Schneider - Collaborator - University of Basel
Marlene Bloechliger - Corresponding Applicant - University of Basel
Michael Bodmer - Collaborator - University of Basel
Raoul Sutter - Collaborator - University Hospital Basel
Sarah Tschudin Sutter - Collaborator - University Hospital Basel
Stephan Ruegg - Collaborator - University of Basel
Theresa Burkard - Collaborator - University of Basel