Efficacy of Chloramphenicol in the Treatment of Neonatal and Infantile Meningitis: a Study of 70 Cases

The efficacy of chloramphenicol in the treatment of 21 neonates and 9 infants with proven meningitis and 37 neonates and 3 infants with suspected meningitis was evaluated from mortality and morbidity data, and by assay of the drug in serum and cerebrospinal fluid. Minimum inhibitory concentrations (MICs) were established for ten isolates. 25% of neonates and 50% of infants had subtherapeutic concentrations of chloramphenicol in serum or cerebrospinal fluid. Dosage was less than that currently recommended in over half of these subjects. Mild toxicity (reversible thrombocytopenia) was observed in only 1 of 20 babies being treated at the recommended dose. Toxic reactions, including the grey-baby syndrome, occurred in 10 babies receiving higher doses. In 4 cases, doses up to ten times that prescribed had been given, and death of 1 baby was attributable in part to chloramphenicol toxicity. 5 of 21 neonates and 1 of 9 infants with bacteriologically proven meningitis died, an overall mortality of 20%. Those infected with gram-negative bacteria had a higher mortality than those infected with gram-positive bacteria (p less than 0 . 05). 21% of the survivors had neurological sequelae. Therapeutic concentrations of chloramphenicol will be achieved in serum and cerebrospinal fluid with daily doses of 25 mg/kg in preterm and term infants during the first week of life and 37 . 5-50 mg/kg for older term babies. The drug should be assayed at 48-hour intervals, to maintain concentrations in the therapeutic, non-toxic range. Dosage should be increased when the peak serum concentration falls below 20 mg/l and decreased when the trough serum concentration exceeds 15 mg/l or the peak concentration exceeds 30 mg/l.