Neurotoxicity of carbapenem antibacterials.
Similar to other beta-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 beta-lactam antibacterials seems to be caused by an interaction with gamma-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.
Norrby
S R
SR
Department of Infectious Diseases, University of Lund, Lund University Hospital, Sweden.
D000818:Animals; D015780:Carbapenems / Q000009:adverse effects*; D002648:Child; D015377:Cilastatin / Q000009:adverse effects; D006801:Humans; D015378:Imipenem / Q000009:adverse effects; D000077731:Meropenem; D018079:Receptors, GABA / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced*; D013845:Thienamycins / Q000009:adverse effects
D015780:Carbapenems; D018079:Receptors, GABA; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077731:Meropenem