Disposition of chloramphenicol in low birth weight infants

Abstract

Although infrequently an antibiotic of first choice for neonates, chloramphenicol (CL) may be indicated in selected instances of infection caused by aminoglycoside-resistant enterobacteriaciae, anaerobes, and ampicillin-resistant Haemophilus influenzae. Use of CL in neonates has been limited since the recognition that vascular collapse may occur as a consequence of dosage regimens tolerated by adults. With an assay that detects only active CL, we studied drug disposition in 13 low birth weight infants, eight between 1 and 8 days of age (group I), and five between 11 days and 8 weeks of age (group II). Peak serum CL concentrations ranged from 11.2 to 36.2 microgram/ml in group I and from 10.0 to 36.2 microgram/ml in group II, at doses ranging from 15 to 50 mg/kg/day, and 25 to 50 mg/kg/day, in groups I and II, respectively. Serum CL half-lives (T1/2) ranged from 10 to 36 hours in four of the eight group I patients; three of the remaining patients had T1/2 greater than 48 hours and the fourth patient accumulated CL in the interval between doses. T1/2 in group II ranged from 5.5 to 15.7 hours. Observed differences in T1/2 between groups I and II were statistically significant (P = .05) and could not be accounted for by factors other than postnatal age. These preliminary data suggest that although there appears to be an inverse relationship between CL T1/2 and postnatal age, there is sufficient variability in serum levels that monitoring must be performed in low birth weight infants treated with this drug.