Western blot analysis of the fetal IgM response to Treponema pallidum antigens was examined among 39 pairs of maternal/infant sera; this included 12 mothers and infants with active syphilis (group I), 9 mothers with active syphilis and their infants with uncertain infection (group II), and 18 mothers treated for syphilis before delivery and their asymptomatic infants (group III). A fetal IgM response to T. pallidum antigens with apparent molecular masses of 72, 47, 45, 42, 37, 17, and 15 kDa was observed among sera of infants with congenital syphilis. Fractionation of sera into IgM and IgG components by high performance liquid chromatography confirmed that fetal IgM antibodies in every case were directed specifically against a 47-kDa antigen. Two asymptomatic infants from group II also showed serum IgM reactivities with the 47-kDa antigen, thereby appearing to confirm in utero infection. The combined data suggest that fetal serum IgM reactivity with the 47-kDa antigen of T. pallidum can be used as an important molecular marker for the diagnosis of congenital syphilis.

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The pharmacokinetics of cefotaxime were determined in newborn infants who were 1 to 7 days of age. Mean peak serum concentrations of 116 and 132 ,ug/ml were observed at completion of a 10-min intravenous infusion of 50 mg of cefotaxime per kg in low and average birth weight infants, respectively. The mean elitnination half-lives were 4.6 and 3.4 h and rates of clearance from serum were 23 and 44 ml/min per 1.73 m2, respectively. A dosage schedule for cefotaxime in newborn infants is presented.Cefotaxime has broad antibacterial activity against gram-positive and gram-negative microorganisms. Although approved by the Food and Drug Administration for use in adults only, cefotaxime has potential for the therapy of neonatal infections because it is effective in vitro (3) and in experimental meningitis (2) against group B streptococci and gram-negative enteric bacilli, the pathogens responsible for most neonatal sepsis and meningitis cases.The purpose of this study was to determine the pharmacokinetics of cefotaxime in newborn infants. Thirty infants were selected from the nursery of Parkland Memorial Hospital, Dallas, Tex. All infants were receiving ampicillin and gentamicin for suspected sepsis. After informed, written parental consent was obtained, a single 50-mg/kg dose of cefotaxime was given intravenously over a 10-min period. The dose was administered in addition to the antibiotics already prescribed. There were 17 male and 13 female infants enrolled in the study. Approximately 0.2 ml of blood was obtained by heelstick technique at 0 (end of the infusion), 0.5, 1, 2, 4, and 6 h after the infusion. The serum was stored-at -20°C until assayed within 4 days of collection. A single, untimed urine specimen was obtained during the 6-h study period.Concentrations of cefotaxime in serum and urine were assayed by an agar-disk diffusion method, using Escherichia coli ATCC 10536 as the test strain. The minimal inhibitory concentrations of cefotaxime and desacetyl cefotaxime for this strain were 0.015 and 0.25 ,ug/ml, respectively. The lowest concentration of drug measured by the bioassay technique was 1.25 ,ug/ml. Inactivation of ampicillin was accomplished by incubating the specimen for 15 min with 8,000 U of penicillinase (Difco Laboratories) per ml in 1% phosphate buffer (pH 6.0). This procedure did not affect the activity of cefotaxime. The dilutions of the samples used for assay eliminated an inhibitory effect of the aminoglycoside on the E. coli (gentamicin minimal inhibitory concentration, 1.5 pLg/ml). Based on analysis of 15 cefotaxime reference curves, the error of the bioassay was ±7% for concentrations of 1.25 to 20 ,ug/ml.The serum concentration-time curves for each subject were analyzed by nonlinear leastsquares regression analysis with the AUTOAN program (4). The curves were fitted to the bioexponential equation C(t) = Aea + Be-', where C(t) is the serum concentration (micrograms per milliliter) at time t, A and B are preexponential terms in units of concentration, and a and 1B are hybrid first-order rate co...

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Ceftriaxone pharmacokinetics were determined in 40 newborn infants who were 1 to 45 days of age. Mean peak plasma concentrations of 136 to 173 ,ug/ml were observed at the completion of a 15-min intravenous infusion of 50 mg of ceftriaxone per kg. Mean half-life values were 5.2 to 8.4 h, and mean plasma clearances were 0.7 to 1.8 mlmin. Rectal swab cultures from 14 of 16 infants had either reduced numbers of aerobic and anaerobic bacteria or no growth during therapy. A once-daily dosage schedule is suggested for ceftriaxone therapy in newborn infants.Ceftriaxone is exceedingly active in vitro against group B streptococci (90% minimal inhibitory concentration [MIC90], 0.12 ,ug/ml) (6) and gram-negative enteric bacilli (MIC90, 0.06 .ag/ml) (7), the two principal pathogens of neonatal sepsis and meningitis. In experimental group BIII streptococcal meningitis in rabbits, ceftriaxone produced cerebrospinal fluid bactericidal titers of 1:64 and a reduction in organisms of 4.6 loglo CFU/ml of cerebrospinal fluid after 9 h of continuous infusion therapy (6). Similarly, in experimental Escherichia coli Kl meningitis, cerebrospinal fluid bactericidal titers of 1:64 and a decline in concentrations of bacteria of 4.8 log1o CFU/ml of cerebrospinal fluid were observed (6). These results in the rabbit meningitis model were comparable or superior to results obtained with all other antimicrobial agents (netilmicin, ampicillin, cefotaxime, cefoperazone, moxalactam, and ceftazidime) studied in our laboratory (4-6).Ceftriaxone pharmacokinetics were determined in newborn infants who had suspected sepsis at Parkland Memorial Hospital, Dallas, Tex. After informed parental consent was obtained, a single dose of 50 mg of ceftriaxone per kg was administered intravenously over a period of 15 min to 26 infants. Multiple doses of 50 mg/kg were given every 12 h for 4 to 10 days to 14 infants, 5 of whom received some doses intramuscularly. The infants were concomitantly treated with ampicillin. Approximately 0.2 ml of blood was obtained from each of the 26 infants by heel-stick technique just before the ceftriaxone dose and at 0 (end of infusion), 0.5, 1, 2, 4, and 6 h after infusion. In infants who received multiple doses, plasma specimens were obtained at initiation and completion of therapy, except in one infant, who had specimens obtained on separate occasions because therapy was given for 10 days. A single untimed urine specimen was obtained during the 6-h study period.Ceftriaxone concentrations in plasma and urine were assayed by an agar disk diffusion method with Escherichia coli (RO1346) as the test strain (1). The smallest concentration detectable by this method was 0.75 ,ug/ml. Inactivation of ampicillin was accomplished by incubating the specimens for 15 min with 8,000 U of penicillinase (Difco Laboratories, Detroit, Mich.) per ml in 1% phosphate buffer (pH 6.0). Laboratory standards and plasma samples were identically processed with pooled plasma from healthy donors. Urine was diluted in 1% phosphate buffer (pH 6.0) and compared...