High Compared With Standard Gentamicin Dosing for Chorioamnionitis: A Comparison of Maternal and Fetal Serum Drug Levels

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Abstract
To compare umbilical cord and maternal serum peak gentamicin concentration, gentamicin elimination, and clinical outcomes between women who received once-daily compared with standard, thrice-daily dosing for clinical chorioamnionitis. We randomly assigned 38 laboring women, at least 34 weeks gestation, with clinical chorioamnionitis, into 1 of 2 gentamicin dosing groups: 5.1 mg/kg every 24 hours (once-daily; n = 18), or 120 mg followed by 80 mg every 8 hours (standard; n = 20). We measured maternal serum peak and delivery gentamicin concentrations and cord serum levels at delivery. Polynomial curve fitting was used to summarize gentamicin elimination. We also compared maternal and neonatal outcomes. Demographic characteristics of the 2 groups were similar. Median maternal peak gentamicin levels were higher with once-daily (18.2 microg/mL) compared with standard dosing (7.1 microg/mL) (P < .001). Maternal serum levels decreased below 2 microg/mL by 10 hours in the once-daily group and by 5 hours in the standard dosing group. Extrapolated peak cord serum levels were 6.9 microg/mL in the once-daily and 2.9 microg/mL in the standard dosing arm. Cord levels decreased below 2 microg/mL by 10 hours in the once-daily and by 5 hours in the standard dosing group. We found no differences in maternal or neonatal outcomes. Peak maternal serum gentamicin levels ranged from 13 to 25 microg/mL after a dose of 5.1 mg/kg. Single-dose gentamicin resulted in fetal serum peak levels that were closer to optimal neonatal values. Gentamicin clearance in the term fetus was similar to published values for the newborn infant. No adverse effects of high-dose therapy were noted.