A review of synergistic nephrotoxicity associated with the concomitant administration of aminoglycoside and cephalosporin antibiotics is presented. A combination of these antibiotics is frequently administered in clinical practice as initial therapy in the treatment of gram-negative bacillary infection. The nephrotoxicity associated with cephalosporin/aminoglycoside administration in humans has been characterized as an acute tubular necrosis. Attempts to investigate this type of toxicity in animals using the rat as the model have revealed that the rat kidney is not affected by the aminoglycoside/cephalosporin combination in the same manner as the human kidney. The results from studies using the rat were not predictive of the nephrotoxicity encountered in humans, and cephalosporins actually appear to protect the rat from aminoglycoside-induced renal damage. The mechanism of the protective effect in rats and the toxic effects in man remain unknown. A species differentiation clearly exists between man and rats with respect to the nephrotoxic effects of aminoglycoside/cephalosporin combinations. The weight of present evidence indicates that, in man, an aminoglycoside/cephalosporin combination is synergistically nephrotoxic.
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