Newborn infants, especially those born prematurely, cannot adequately conjugate chloramphenicol to form the glucuronide; they also have depressed rates of glomerular and tubular secretion. Because of these metabolic deficiencies, high levels of free chloram-phenicol may accumulate and cause a potentially fatal toxic reaction, the gray baby syndrome. This syndrome is characterized by abdominal distention, vomiting, progressive cyanosis, irregular respiration, hypothermia, and vasomotor collapse. The mortality rate is high. The syndrome also has been observed in older children and is associated with high serum levels of chloramphenicol.
The presence of multiple metabolites in the serum of neonates treated with chloramphenicol suggests that the biotransformation of chloramphenicol takes place by multiple routes to include oxidation, reduction, and conjugation. The presence of particular metabolites does not appear to correlate with toxicity.
The most publicized adverse affects are those involving the hematopoietic system; they are manifested by toxic bone marrow depression or idiosyncratic aplas-tic anemia. The bone marrow depression is dose related and is seen most frequently when daily doses exceed 4 g and plasma concentrations exceed 25 ¡g/mL. The bone marrow depression is characterized by anemia, sometimes with leukopenia or thrombocytopenia, but it is reversible on discontinuation of chloramphenicol.
Aplastic anemia occurs in only about 1 in 24,000 to 40,000 cases of treatment. It is not a dose-related response and can occur either while the patient is taking chloramphenicol for days to months after completion of therapy. The aplastic or hypoplastic response involves all cellular elements of the marrow and is usually fatal. The mechanism is not known, but it occurs most frequently with oral or ocular administration.
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