Antibiotic Toxicity in Newborn and Adult Rats

Abstract

The occurrence of chloramphenicol toxicity in the newborn and premature infant is a well-documented clinical entity that occurs if a critical dose or blood level is exceeded.^1-6 The cardiovascular collapse and death are associated with elevated levels of chloramphenicol, which are the result of immature renal excretory functions and also of the immature hepatic conjugating mechanism. These mechanisms are well developed in the older child and adult and hence this type of toxicity has not been described in patients receiving usual therapeutic doses of chloramphenicol. In patients with hepatic cirrhosis and severe renal disease, however, there is retention of chloramphenicol and its metabolic product.⁷ The evaluation of any experimental drug prior to clinical use requires animal toxicity studies. The effect on the newborn animal is not routinely appraised however. The finding that chloramphenicol is 14 times more toxic to the newborn than the adult rat⁸ and the