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October 13, 2015; 85 (15) Views & Reviews

Seizures as adverse events of antibiotic drugs

A systematic review

Raoul Sutter, Stephan Rüegg, Sarah Tschudin-Sutter
First published September 23, 2015, DOI: https://doi.org/10.1212/WNL.0000000000002023
Raoul Sutter
From the Clinic for Intensive Care Medicine (R.S.), the Division of Clinical Neurophysiology, Department of Neurology (R.S., S.R.), and the Division of Infectious Diseases and Hospital Epidemiology (S.T.-S.), University Hospital Basel, Switzerland.
MD
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Stephan Rüegg
From the Clinic for Intensive Care Medicine (R.S.), the Division of Clinical Neurophysiology, Department of Neurology (R.S., S.R.), and the Division of Infectious Diseases and Hospital Epidemiology (S.T.-S.), University Hospital Basel, Switzerland.
MD
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Sarah Tschudin-Sutter
From the Clinic for Intensive Care Medicine (R.S.), the Division of Clinical Neurophysiology, Department of Neurology (R.S., S.R.), and the Division of Infectious Diseases and Hospital Epidemiology (S.T.-S.), University Hospital Basel, Switzerland.
MD, MSc
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Citation
Seizures as adverse events of antibiotic drugs
A systematic review
Raoul Sutter, Stephan Rüegg, Sarah Tschudin-Sutter
Neurology Oct 2015, 85 (15) 1332-1341; DOI: 10.1212/WNL.0000000000002023

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Abstract

Objective: Antibiotic drugs are commonly associated with seizures. Tailoring antibiotics to the individual risk for seizures is challenged as avoidance of certain antibiotic classes may no longer be possible due to the emergence of resistant bacteria. We performed a systematic review regarding the current evidence for seizures associated with all antibiotic classes, their underlying mechanisms, and predisposing factors.

Methods: The medical search engine PubMed was systematically screened to identify articles in English published between 1960 and 2013. All study designs were considered and evidence was assessed.

Results: We included 143 articles involving 25,712 patients and 25 different antibiotics. Evidence for antibiotic-related symptomatic seizures is low to very low, mainly deriving from studies regarding β-lactams, especially unsubstituted penicillins and fourth-generation cephalosporins, as well as carbapenems, mainly imipenem, all administered in high doses or in patients with renal dysfunction, brain lesions, or known epilepsy. Evidence regarding symptomatic seizures from fluoroquinolones only relies on case reports and case series with most reports for ciprofloxacin in patients with renal dysfunction, mental disorders, prior seizures, or coadministered theophylline.

Conclusions: Evidence for an association between antibiotic drugs and symptomatic seizures is low to very low (evidence Class III–IV). Despite this, numerous reports point to an increased risk for symptomatic seizures especially of unsubstituted penicillins, fourth-generation cephalosporins, imipenem, and ciprofloxacin in combination with renal dysfunction, brain lesions, and epilepsy. During administration of such antibiotics in patients with particular predispositions, close monitoring of serum levels is advocated. As most seizures associated with cephalosporins are nonconvulsive, continuous EEG should be considered in patients with altered levels of consciousness.

GLOSSARY

AAN=
American Academy of Neurology;
AED=
antiepileptic drug;
ECT=
electroconvulsive therapy;
FDA=
Food and Drug Administration;
GABA=
γ-aminobutyric acid;
NCSE=
nonconvulsive status epilepticus;
SE=
status epilepticus;
VPA=
valproic acid

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received March 7, 2015.
  • Accepted in final form June 16, 2015.
  • © 2015 American Academy of Neurology
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