The use of antibiotics (drugs to cure patients with bacterial infections) has repeatedly been associated with the occurrence of epileptic seizures, meaning abnormal activity in the brain affecting a personÂ’s behaviour, consciousness or appearance. Various types of antibiotics have been associated with different risks of epileptic seizures.
Generally, the risk of epileptic seizures seems to be highest when high doses of antibiotics are used or when patients have impaired kidney function, underlying brain disorders like epilepsy or brain infections, or infections with bacteria being distributed throughout the body. Our interest lies in the possible association of antibiotic therapy with epileptic seizures in patients with epilepsy, when taken at usual outpatient doses and prescribed by the general practitioner. The goal of this study is to quantify the risk of epileptic seizures in children and adult patients who suffer from epilepsy and are newly prescribed oral (taken by mouth) antibiotics by a general practitioner, compared to patients with epilepsy who are not prescribed antibiotics at that time. We further plan to investigate the potential role of the type of antibiotic, the antibiotic dose, the patientsÂ’ age, kidney function, underlying type of infection, and pre-existing risk factors for epileptic seizures apart from epilepsy.
We will estimate the cumulative incidence of epileptic seizures in patients with epilepsy aged 16 years 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 with epilepsy not prescribed antibiotics at that time. We will divide the study period (January 1, 1997 and December 31, 2018) into twenty-two 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, additional risk factors for epileptic seizures apart from epilepsy (drug or alcohol dependence, metabolic disturbances, brain disorders), underlying infection type, prescribed antibiotic type, and a proxy for severity of epilepsy (number of prescribed anticonvulsants, number of seizures in the year prior to the antibiotic prescription or the comparison date of the comparison group). 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.
In a sensitivity analysis among CPRD patients linked to HES APC, we will repeat the main analysis (estimation of cumulative incidence of epileptic seizures in exposed and unexposed patients, calculation of risk ratio of epileptic seizures in exposed vs. unexposed patients) applying a stricter definition of the outcome, namely a hospitalisation with a recorded ICD-10 code of epileptic seizures as the primary reason for hospital admission in HES APC data.
Epileptic seizures as recorded using Read codes in CPRD GOLD data, and in a sensitivity analysis, as recorded using ICD-10 codes in HES APC data.
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Marlene Rauch - Corresponding Applicant - University of Basel
Christoph Meier - Collaborator - University of Basel
Lea Barone - Collaborator - University Hospital Basel
Raoul Sutter - Collaborator - University Hospital Basel
Sarah Tschudin Sutter - Collaborator - University Hospital Basel
Stephan Ruegg - Collaborator - University of Basel
Christoph Meier - Collaborator - University of Basel
HES Admitted Patient Care