Neurotoxicity of Carbapenem Antibacterials

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Abstract
Similar to other β-lactam antibacterials, carbapenems have a neurotoxic potential that seems to be higher than that of the penicillins and cephalosporins. Seizures have been reported in several large studies of patients treated with imipenem/cilastatin. However, it seems clear that the main factor increasing the risk of neurotoxicity with imipenem/cilastatin is administration of excessive dosages relative to bodyweight and/or renal function. If the manufacturer’s dosage recommendations are followed, the risk of seizures in patients receiving this combination is minimal. With meropenem, a newly registered carbapenem, the safety margin with respect to neurotoxic reactions has been increased compared with imipenem and meropenem can be used at higher doses than imipenem/cilastatin. Since the neurotoxicity of β-lactam antibacterials seems to be caused by an interaction with γ-aminobutyric acid (GABA) receptors, other drugs with a similar mechanism of action, such as fluoroquinolone antibacterials, should be used with caution when combined with carbapenems.