The concentrations of five cephalosporins and amoxicillin in breast milk were studied in 42 voluntarily participating lactating mothers using standard assay methods. Each mother received one single dose of 1 g of either an orally or intravenously administered antibiotic. Amoxicillin, cephalexin, and cefadroxil were given orally, and peak milk concentrations averaged 0.81 +/- 0.33 microgram/ml at 5 hours, 0.50 +/- 0.23 microgram/ml at 4 hours, and 1.64 +/- 0.73 microgram/ml at 6 hours, respectively. Cephalothin, cephapirin and cefotaxime were given as an i.v. bolus injection, and peak milk concentrations at 2 hours averaged 0.47 +/- 0.14 microgram/ml, 0.43 +/- 0.16 microgram/ml and 0.32 +/- 0.09 microgram/ml, respectively. The high concentrations of cefadroxil can be explained by its low rate of elimination and higher fat solubility. Milk/serum ratios for all antibiotics were increasing as serum concentrations were diminishing, especially with cephalothin and cephapirin whose serum concentrations are rapidly declining. The significance of bactericidal concentrations in breast milk remains to be evaluated.
The penetration of ceftriaxone into the fetus at parturition was studied in 17 subjects. Despite its high protein binding, ceftriaxone quickly reached the umbilical cord blood, amniotic fluid, and placenta, achieving substantial concentrations, which then disappeared, with elimination half-lives of approximately 6 h, identical to that of the mother. The elimination half-life of ceftriaxone of 5 to 6 h in these mothers was somewhat shorter than that reported for normal subjects. The concentrations of ceftriaxone achieved in fetal tissues were sufficient for therapeutic effects. The penetration of ceftriaxone into milk was studied 3 days postpartum in 20 other patients. This antimicrobial agent entered breast milk rapidly and disappeared with a half-life of 12 to 17 h. The concentrations achieved were only 3 to 4% of those in maternal serum and were most likely of little clinical relevance.Broad-spectrum cephalosporins could prove to be highly useful for the prophylaxis or treatment of maternal or fetomaternal infections or both (9). Since ceftriaxone has exhibited no serious toxicity in early use and since animal studies indicate no teratogenicity, one may anticipate the use of this drug in pregnancy (9). We, therefore, investigated in 17 subjects the time course of the disappearance of ceftriaxone from the mother and its distribution into the umbilical cord blood, placenta, amniotic fluid, and urine of the neonate. In 20 additional subjects, we assessed the distribution into breast milk.MATERIALS AND METHODS Study protocols. (i) Distribution of ceftriaxone to the fetus. Seventeen healthy women aged 22 to 42 years, at 38 to 41 weeks of gestation, volunteered for this phase of the study after giving informed consent. These patients were hospitalized for the premature rupture of membranes. All were in active labor. Delivery was induced by an intravenous infusion of oxytocin in 13 patients. Caesarean section was performed in four. Each patient received 2.0 g of ceftriaxone dissolved in a total volume of 20 ml of sterile water as an intravenous bolus over 2 to 5 min. The interval from dosing to tissue sampling was determined by the time of expulsion or of removal of the fetus. The characteristics of this group are shown in Table 1. Maternal and umbilical cord blood, placenta samples, and an aliquot of amniotic fluid were collected immediately after delivery. Placenta samples were extensively washed in sterile normal saline, weighed, and homogenized in a Colwarth Stomacher 80 with a triple weight in up to 3 ml of Sorensen buffer, pH 7.2. In addition, in five newborn infants, the first voided urine was collected for analysis.(Ui) Penetration of ceftrlaxone into milk. Twenty healthy mothers aged 19 to 34 years, who had been breast feeding for the 2 preceding days, participated in the study after giving informed consent. On day 3 postpartum, a 1.0-g dose of ceftriaxone in a volume of 10 ml was administered by intravenous bolus over 2 to 5 min to 10 mothers and by intramuscular injection in a volume of 4 ml to the remaini...
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