Mechanism of the Mitochondrial Respiratory Toxicity of Cephalosporin Antibiotics
The beta-lactam antibiotics exert their antimicrobial action by acylating and inactivating several functionally important bacterial membrane-bound proteins (Waxman and Strominger, 1983). This action is highly specific, and the beta-lactams have, in general, very favorable toxic- therapeutic ratios. However, several cephalosporins (Tune, 1986), and the new thienamycin antibiotic imipenem (Bimbaum et al., 1985), can cause acute renal failure when given under high-risk conditions. This toxicity is seen as an acute proximal tubular necrosis (Silverblatt et al., 1970), occurs in proportion to the concentrative uptake of the antibiotics by the tubular cell (Tune, 1975), and is prevented by inhibitors of this secretory transport (Tune and Fravert, 1980a).
KeywordsMitochondrial Respiration Substrate Uptake Potassium Cyanide Mitochondrial Toxicity Carbonyl Cyanide
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