1
Sutter et al.
Table e-4. Publications regarding carbapenems and seizures or status epilepticus
Reference / Year / Design (AAN Class of evidence) / Number of patients / Dosage / Contributing factors other than antibiotics / Reported symptomatic seizure(s)Imipenem
Chastre et al. 1 / 2008 / Randomized multicenter study
(Class III) / 525 patients / 263 with 1.5-2 g imipenem per day and 262 patients with doripenem 1.5 g per day / 21 with seizure history in each group / 3.8% with imipenem/cilastatin had seizures vs. 1.1% with doripenem
Linden 2 / 2007 / Retrospective study
(Class IV) / 106037 patients / 2567 patients with imipenem (dosage not provided) compared to patients with comparator agents / 415 with meningitis / 0.23% with seizures and no meningitis (vs. 0.07% seizures in patients with meropenem)
Koppel et al. 3 / 2001 / Retrospective study
(Class III) / 75 patients / Dosage not provided / 58 patients had conditions causing breakdown of the blood-brain barrier / 5% had seizures. Seizure incidence of patients on or off imipenem did not differ
Pestotnik et al. 4 / 1993 / Prospective observational study
(Class IV) / 1951 patients with imipenem / Computerized monitoring and recommend action of dosage changes of imipenem in patients with renal insufficiency / CNS disease (6%), seizure disorders (0.6%), and abnormal renal function (70%) / Seizures in 0.2%, all patients were receiving dosages that were excessive with respect to their renal function
Calandra et al. 5 / 1988 / Retrospective study
(Class IV) / 1754 patients with imipenem / 2-3 g imipenem per day / Of patients with seizures, 21 had seizure history, 13 had stroke, 5 brain trauma, 4 brain tumors, 3 multiple sclerosis, 3 anoxic brain damage, 1 malformation, and 2 had brain atrophy / 3% had seizures (mostly tonic-clonic) and in 0.9% of them the seizures were judged by the investigators to be possibly, probably, or definitely related to imipenem
Lane et al. 6 / 1996 / Retrospective study
(Class IV) / 128 patients with imipenem / 1-2 g imipenem per day / 2 with brain lesions, 1 with Lafora disease, and 1 with renal insufficiency / 3% had seizures
Eng et al. 7 / 1989 / Case series
(Class IV) / 5 patients / 1-4 g imipenem per day / None / Seizures (mostly “grand mal”)
Job et al. 8 / 1990 / Case reports
(Class IV) / 2 patients / 4 g imipenem per day / Both with old strokes and prior treatment with cefotaxime or mezlocillin / Seizures
Leo et al. 9 / 1991 / Case reports
(Class IV) / 2 patients / 1 g imipenem per day / Both with multi organ failure, 1 with prior treatment with cefazolin, and tobramycin / Repetitive convulsive Seizures
Semel et al. 10 / 1991 / Case reports
(Class IV) / 3 patients / 1.5-2 g imipenem per day / Additional treatment with theophyllin / Seizures
Hunter et al. 11 / 1993 / Case report
(Class IV) / 1 patient / 4 g imipenem per day / None / Generalized tonic-clonic seizure
Galante et al. 12 / 2009 / Case report
(Class IV) / 1 patient / 1 g imipenem once prior transurethral resection of the prostate / Simultaneous local administration of anesthetic agents / Repetitive seizures
Meropenem
Tanaka et al. 13 / 2013 / Retrospective study
(Class III) / 745 patients / 2-3 g meropenem per day compared to patients with cefepime / All with brain disorders / 0.54% with convulsive seizures (vs. 2.7% with convulsive seizures)
Linden 2 / 2007 / Retrospective study
(Class IV) / 106037 patients / 6154 patients with 1.5-3 g meropenem per day compared to patients with comparator agents / 415 with meningitis / 0.07% with seizures and no meningitis (vs. 0.23% with seizures in patients with imipenem)
Cunha 14 / 1999 / Retrospective study
(ClassIV) / 843 patients / 1.5-3 g meropenem per day / Elderly patients with renal insufficiency / 0.1% with seizures
Coves-Orts et al. 15 / 2005 / Case report
(Class IV) / 1 patient / 3 g meropenem per day / Known epilepsy / Generalized tonic-clonic seizures occurring after meropenem decreased levels of valproic acid levels
Fudio et al. 16 / 2006 / Case report
(Class IV) / 1 patient / 1 g meropenem per day / Known epilepsy treated with valproic acid / Seizures after meropenem decreased levels of valproic acid levels
Doripenem
Rea-Neto et al. 17 / 2008 / Randomized multicenter study
(ClassIII) / 445 patients / 221 patients with 18 g piperacillin/tazobactam per day and 223 with 1.5 g doripenem per day / Renal insufficiency in 47% with doripenem and 41.2% with piperacillin/tazobactam / 1.2% with doripenem had seizures vs. 2.7% with piperacillin/tazobactam
Chastre et al. 1 / 2008 / Randomized multicenter study
(ClassIII) / 525 patients / 262 patients with doripenem 1.5 g per day and 263 with 1.5-2 g imipenem per day / 21 with seizure history in each group / 1.1% with doripenem had seizures vs. 3.8% with imipenem/cilastatin
Ertapenem
Seto et al. 18 / 2005 / Case report
(Class IV) / 1 patient / 1 g ertapenem per day / Chronic renal insufficiency and spinal anesthesia with bupivacaine 1.5 day prior to first seizure / Repetitive generalized tonic-clonic seizures
Saidel-Odes et al. 19 / 2006 / Case reports
(Class IV) / 2 patients / 0.5 g ertapenem per day / Both with old stroke / Both with repetitive seizures
Lunde et al. 20 / 2007 / Case report
(Class IV) / 1 patient / 2 g ertapenem per day / Known epilepsy after traumatic brain injury treated with valproic acid / Generalized tonic-clonic seizure
Fica et al. 21 / 2008 / Case reports
(Class IV) / 3 patients / 1 g ertapenem per day / All with renal insufficiency / All with convulsive seizures
Liao et al. 22 / 2010 / Case reports
(Class IV) / 2 patients / 0.5-1 g ertapenem per day / Both with known epilepsy treated with valproic acid and 1 with history of intracerebral hemorrhage / 1 with generalized tonic-clonic seizures after ertapenem decreased levels of valproic acid
AAN = American Academy of Neurology; SE = status epilepticus; CNS = central nervous system
References
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