Ceftazidime pharmacokinetics in preterm infants: Effects of renal function and gestational age*

Anker, John N. van den; Schoemaker, Rik C.; Hop, Wim C. J.; Heijden, Bert J. van der; Weber, Allan; Sauer, Pieter J. J.; Neijens, H. J.; Groot, Ronald de

doi:10.1016/0009-9236(95)90021-7

Cited by 76 publications

(42 citation statements)

References 41 publications

(4 reference statements)

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“…The ceftazidime/inulin clearance ratio was 0.72 for both groups. Glomerular filtration rates, as measured by inulin clearances, were similar in both groups and were all within the same range reported by us previously (21). Values for total body clearance, apparent volume of distribution, serum elimination half-life, and inulin clearance were not significantly different for both groups.…”

Section: Resultssupporting

confidence: 88%

“…Pharmacokinetic studies are therefore necessary to optimize dosing regimens. We have previously demonstrated that the use of the lowest recommended dose for preterm infants, i.e., 25 mg of ceftazidime per kg given intravenously twice daily, resulted in high concentrations of ceftazidime in serum throughout the entire dosing interval (21). However, serious side effects were not seen.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that the pharmacokinetic behavior of ceftazidime in preterm infants is strongly dependent on GA and postnatal age. At a dosage of 25 mg of ceftazidime per kg given intravenously twice daily, high trough levels were observed, especially in infants with GAs below 32 weeks (21). High concentrations of beta-lactam antibiotics in serum and tissues do not result in a more rapid killing of bacteria (4), but they may lead to neutropenia and the impairment of cellular and humoral immune responses (14).…”

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confidence: 99%

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Once-daily versus twice-daily administration of ceftazidime in the preterm infant

Anker

Schoemaker

Heijden

et al. 1995

Antimicrob Agents Chemother

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Ceftazidime pharmacokinetics in 28 preterm infants (gestational ages, 25.6 to 31.9 weeks) were studied on day 3 of life. Patients with suspected septicemia were randomized on day 1 of life in two groups. One group (n ‫؍‬ 13) was administered 25 mg of ceftazidime per kg of body weight once daily, and the other (n ‫؍‬ 15) was given 25 mg of ceftazidime per kg twice daily. Both groups also received 25 mg of amoxicillin per kg twice daily. Blood samples were collected on day 3 of life with an arterial catheter at 0, 0.5, 1, 2, 4, 8, and 12 h after an intravenous bolus injection. An additional blood sample was taken at 24 h from the group dosed once a day. High-performance liquid chromatography was used to determine serum ceftazidime concentrations. The pharmacokinetics of ceftazidime were best described by using a one-compartment model. The half-life for the elimination of the drug from serum, apparent volume of distribution, total body clearance of ceftazidime, and inulin clearance were not significantly different for both groups. The ceftazidime/inulin clearance ratio was 0.72 for both groups. However, trough concentrations in serum for the twice-daily group were significantly (P < 0.001) higher (42.0 ؎ 13.4 mg/liter) than those for the once-daily group (13.1 ؎ 4.7 mg/liter). The latter concentrations were all still substantially higher than the MIC of ceftazidime for major neonatal pathogens. We conclude that the currently recommended dosage of 25 mg of ceftazidime per kg twice daily for preterm infants with gestational ages below 32 weeks may be adjusted during the first days of life to one daily dose at 25 mg/kg, provided that for the empirical treatment of septicemia, amoxicillin at 25 mg/kg is also given twice daily.Ceftazidime, an expanded-spectrum cephalosporin, is commonly used in the treatment of bacterial infections in the newborn (5). The currently recommended dosage regimen of ceftazidime for preterm infants less than 4 weeks old and whose birth weights are below 1,200 g is 25 to 100 mg/kg of body weight given intravenously twice daily (18). However, these dosage recommendations are based upon few pharmacokinetic data. Previous studies also did not stratify preterm infants according to gestational age (GA) or postnatal age, which has resulted in a substantial variability in pharmacokinetic parameters (3,(11)(12)(13)17). We have previously demonstrated that the pharmacokinetic behavior of ceftazidime in preterm infants is strongly dependent on GA and postnatal age. At a dosage of 25 mg of ceftazidime per kg given intravenously twice daily, high trough levels were observed, especially in infants with GAs below 32 weeks (21). High concentrations of beta-lactam antibiotics in serum and tissues do not result in a more rapid killing of bacteria (4), but they may lead to neutropenia and the impairment of cellular and humoral immune responses (14). We therefore designed a prospective randomized study to evaluate the pharmacokinetic effects of reducing the dosage of ceftazidime from 25 mg/kg twice daily to 25 m...

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Section: Resultssupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Once-daily versus twice-daily administration of ceftazidime in the preterm infant

Anker

Schoemaker

Heijden

et al. 1995

Antimicrob Agents Chemother

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“…In conclusion, the comparative PPK analysis described here (11,23), cefazolin (14), cefoperazone (8,38), cefotaxime (21), ceftazidime (40,44), ceftizoxime (26), ceftriaxone (30,32), flucloxacillin (22), meropenem (46), piperacillin (25), and ticarcillin (10) are low (less than 0.4 liters/kg) in adults due to aqueous solubility. (B) Correlation between protein binding ratio and V. The apparent V was strongly associated with the protein binding ratio.…”

Section: Discussionmentioning

confidence: 80%

“…Fourteen antibiotics were reviewed in 16 studies. The values of antibiotic CL from the literature were divided into two groups: circles indicate PCA of Ն33 weeks or BW of Ն2,000 g for amikacin (36), amoxicillin (11,23), aztreonam (13), cefoperazone (38), cefotaxime (21), ceftazidime (40,44), ceftizoxime (26), ceftriaxone (32), meropenem (46), and piperacillin (25); squares indicate PCA of Ͻ33 weeks or BW of Ͻ2,000 for cefoperazone (8), flucloxacillin (10), piperacillin (25), ticarcillin (11), and vancomycin (12). The figure shows that CL is associated with protein binding ratios and that the relationship between renal CL and protein binding is stronger than that between total CL and protein binding.…”

Section: Discussionmentioning

confidence: 99%