Pharmacokinetics of cefotaxime in newborn infants

Abstract

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...

Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis

“…The mean CL of Ctx in our subjects (0.289 liter/h per kg) was in close agreement with values reported for adults with normal renal function (approximately 0.234 to 0.307 liter/h per kg) after Ctx quantitation by HPLC (16,29). The differences between CL of Ctx in our patients and that in full-term, newborn infants (2,26) were consistent with expected developmental differences in renal function and body mass-water relationships between the two age groups.…”

Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Infants during Extracorporeal Membrane Oxygenation

“…The patient with the lowest t ϾMIC (49%) had negative cultures throughout his ECMO run, while the patients with positive cultures had t ϾMIC values of 90% or higher, but this could have been caused by resistance or lack of efficacy of other concomitant antibiotics. The CTX clearance estimate we found for ECMO patients (0.36 liter/h) was similar to those for non-ECMO-treated full-term neonates, which vary from 0.20 to 0.55 liter/h (6,19,23). The distribution volume, however, was larger than those for non-ECMO patients (1.82 liters versus 0.68 to 1.14 liters) (19,23), which could be caused by hemodilution or capillary leakage of protein-bound drug into the extravascular compartment, especially in the early phase of ECMO (24 to 36 h after cannulation).…”

“…The CTX clearance estimate we found for ECMO patients (0.36 liter/h) was similar to those for non-ECMO-treated full-term neonates, which vary from 0.20 to 0.55 liter/h (6,19,23). The distribution volume, however, was larger than those for non-ECMO patients (1.82 liters versus 0.68 to 1.14 liters) (19,23), which could be caused by hemodilution or capillary leakage of protein-bound drug into the extravascular compartment, especially in the early phase of ECMO (24 to 36 h after cannulation). This increase is consistent with studies on the pharmacokinetics of vancomycin (3) and theophylline (26) during ECMO.…”

Microanalysis of β-Lactam Antibiotics and Vancomycin in Plasma for Pharmacokinetic Studies in Neonates

“…Compared to the data for non-ECMO-treated neonates (15), CTX showed similar clearance, with a twofold increase in the V d , which can be explained by the added volume of the ECMO circuit and edema. AMX clearance did not differ from the clearance found in non-ECMO-treated neonates (18); V d was also slightly increased, but this may have been underesti- With PK software, we were able to construct concentrationtime curves and to calculate individual PK parameters for this neonate, using existing models.…”