GENTAMICIN SERUM CONCENTRATIONS IN NEONATES BORN TO GENTAMICIN-TREATED MOTHERS

Abstract

For the treatment of adult infections with aminoglycosides, divided (three times daily) dosage has been superseded by administration of the total dose once daily. The latter schedule has been found to have better bactericidal effects and lower toxicity than the former. 1–4 Once daily dosing has also been tried in infants and children 5–10 but has yet to be adopted for them as a standard regimen Although aminoglycosides are known to cross the placenta, 11, 12 there is to the best of our knowledge no published information concerning serum aminoglycoside concentrations in neonates whose mothers were treated with the daily dosing regimen. The present communication provides preliminary data on neonatal serum concentrations after different dosing regimens in the mothers. Patients and methods. The subjects studied were 21 healthy, full term neonates whose mothers, admitted in labor, required antibiotic therapy and were treated with ampicillin and gentamicin intravenously to the time of delivery. In 11 mothers gentamicin (240 mg) was given as a single daily dose. In 10 it was administered in divided doses (80 mg 3 times daily). The infants born to mothers in these 2 groups were designated Group I and Group II, respectively. The attending obstetrician on the basis of his or her preference and the stage of labor chose the gentamicin regimen. All mothers in Group I had 1 dose of gentamicin (240 mg) before delivery. In Group II 9 of 10 mothers received a single 80-mg dose. From each infant venous blood was sampled for culture, complete blood count and gentamicin concentration at the time of arrival at the Neonatal Unit. The date and time of mother’s last gentamicin dose were recorded. Serum gentamicin concentration was measured by fluorescence polarization (TDx, Abbott Laboratories, Irving, TX). Student’s t test for parametric data and the Mann-Whitney test for ordinal data and independent samples analyzed data. The level of significance was P < 0.05. Serial data are expressed as mean ± sd. Results. Indications for antibiotic therapy shared in common by mothers belonging to both groups were fever during labor, bacterial endocarditis prophylaxis, suspected chorioamnionitis and premature rupture of membranes. Mean birth weights of infants in the two groups were not significantly different nor were the mean time intervals from mother’s last dose of gentamicin to the sampling of blood from the infants and number of doses given to mothers before delivery (Table 1).Table 1: Gentamicin serum concentrations in neonates and the time intervals from mother’s last antepartum doseMean gentamicin serum concentrations in Group I infants were significantly higher than those in Group II infants: 1.94 ± 0.63 and 0.98 ± 0.45 μg/ml, respectively (P = 0.01). There was no correlation between individual serum concentrations in the infants and the time intervals from their mothers’ last dose (Table 1). Discussion. The data presented in Table 1 reveals that in Group I neonatal gentamicin serum concentration exceeded 2.0 μg/ml in 55% of the infants, which is above the upper limit of recommended trough concentration. 6, 13 These observations are of practical importance because when antibiotics are administered to the mother in treatment of infection, they are often given to the neonate as well to prevent transmitted infection. The present data provide information on expected serum gentamicin values in newborn infants as a result of administration of the drug to the mothers before delivery. They should be considered when the physician is planning to treat the infant with a regimen containing gentamicin. If a single daily dosing regimen is to be adopted in obstetric care, neonatal gentamicin serum monitoring and adjusted dosing should be performed. For the present it would seem best to adhere to the divided dose regimen when administering aminoglycosides to the mothers in the setting discussed.