119 IN VITRO NEURÖTOXICITY OF ANTIBIOTICS

Prediction, measurement, and monitoring of neurotoxicity of antibacterial agents are extremely difficult. We studied the effects of antibiotics on growth and differentiation in dissociated rat brain cell cultures. Drugs were added from 7 to 14 days in cultures (DIC) in order to attain concentrations representing 10 and 2 times the levels reached by intraventricular antibiotic administration. At DIC 14, 21 and 24 the following evaluations were performed and compared to controls: content of protein and DNA reflecting cell growth, two enzymes of brain cell differentiation and staining for oligodendrocytes and astrocytes. No effects showed penicillin G, amoxicillin, sulbactam, aztreonam and chloramphenicol. Only marginal and always reversible influences produced ceftriaxone, vancomycin and ciprofloxacin. Clear inhibition of both cell growth and cell differentiation with only partial or absent regeneration was induced by cefepime, ceftazidime, cefotaxime, cefuroxime, imipenem, temafloxacin and amikacin. These results are in accordance with other in vitro experiments (bone marrow cells, fibroblasts) and also with clinical findings. We conclude that the sensible use of this model on the cellular level can predict potential neurotoxicity of antimicrobial agents.