Animal models of the epilepsies

Commonly used antibacterial agents may be associated with various neurotoxic reactions. Central nervous system toxicities include seizure disorders, encephalopathy, bulging fontanelles, and neuropsychiatric symptoms. These abnormalities have been associated with the use of the penicillins, cephalosporins, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, metronidazole, isoniazid, rifampin, ethionamide, cycloserine, and dapsone. Cranial nerve toxicities, such as myopia, optic neuritis, deafness, vertigo, and tinnitus, have been associated with the use of erythromycin, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, vancomycin, isoniazid, and ethambutol. Peripheral nerve symptoms consisting of paresthesias, motor weakness, or sensory impairment have been associated with the use of the penicillins, sulfonamides, chloramphenicol, colistin, metronidazole, isoniazid, ethionamide, and dapsone. Neuromuscular blockade has been associated with the use of the tetracyclines, polymyxins, lincomycin, clindamycin, and aminoglycosides. Management generally consists of supportive therapy and immediate discontinuation of therapy with the offending drug.

The neurotoxicity of antibacterial agents.

Evidence for the involvement of GABAA receptor blockade in convulsions induced by cephalosporins

Chemical models of epilepsy with some reference to their applicability in the development of anticonvulsants.

Central nervous system toxicity following administration of beta-lactam antibiotics, of which penicillin is the prototype, is a potential cause of morbidity and mortality. In recent years, important advances have been made in the pathogenesis of antibiotic-related neurotoxicity. This review focuses on the experimental and clinical aspects of neurotoxicity caused by beta-lactam antibiotics. The purpose is to provide an update on the pathogenesis, mechanism, and clinical manifestations of the neurotoxicity, along with an overview of the relationship between antibiotic structure and convulsive action. In particular, some of the prevailing ideas about pathogenesis are highlighted, including theories of the mechanism of pathogencity. A better understanding of antibiotic-related neurotoxicity, as derived from animal models and human clinical experience, would be of value in facilitating more efficient and safer use of antimicrobial compounds.

Neurotoxicity induced by beta-lactam antibiotics: from bench to bedside.

Reports on intrathecal administration of penicillin in treating infections of the central nervous system are becoming numerous. Recently intraventricular injection of penicillin has been employed when meningitis did not respond to parenteral or intrathecal modes of administration. 1 The direct application of penicillin to wounds of the cerebral cortex in the treatment of injury to the head has also been suggested. 2 Our interest in the effect of penicillin on the central nervous system was aroused by observing convulsive seizures following intraventricular injection of the drug in a case of ventriculitis. 3 Experiments were then planned to investigate the effect of the drug when administered intracisternally, intraventricularly and locally to the cerebral cortex either by application to the subdural space or by intracortical injection. Such experiments were performed, and it was observed that certain doses of penicillin so administered to mice, cats, dogs and monkeys gave rise to convulsive manifestations.

William H. Funderburk

Papers

Convulsive factor in commercial penicillin