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Once-daily versus twice-daily administration of ceftazidime in the preterm infant
J N van den Anker1, R C Schoemaker, B J van der Heijden
1Department of Pediatrics, Erasmus University, Rotterdam, The Netherlands.
Insights
Ceftazidime dosing for preterm infants can be reduced to once daily at 25 mg/kg. This maintains therapeutic levels when combined with twice-daily amoxicillin, aiding empirical septicemia treatment.
Area of Science:
- Neonatal pharmacology
- Pediatric infectious diseases
- Clinical pharmacokinetics
Background:
- Neonatal sepsis requires effective antibiotic treatment.
- Ceftazidime is a key antibiotic for neonatal infections.
- Optimizing ceftazidime dosing in preterm infants is crucial for efficacy and safety.
Purpose of the Study:
- To evaluate ceftazidime pharmacokinetics in preterm infants.
- To compare once-daily versus twice-daily ceftazidime dosing.
- To determine if a once-daily regimen maintains therapeutic serum concentrations.
Main Methods:
- Studied 28 preterm infants (25.6-31.9 weeks gestational age) on day 3 of life.
- Administered ceftazidime 25 mg/kg once or twice daily, with amoxicillin 25 mg/kg twice daily.
- Measured serum ceftazidime concentrations via HPLC at multiple time points up to 24 hours.
Main Results:
- Pharmacokinetics followed a one-compartment model; clearance and volume of distribution were similar between groups.
- Twice-daily dosing resulted in significantly higher trough serum concentrations (42.0 mg/L) than once-daily (13.1 mg/L).
- Once-daily trough concentrations remained above the minimum inhibitory concentration for common neonatal pathogens.
Conclusions:
- The recommended twice-daily ceftazidime dose (25 mg/kg) for preterm infants (<32 weeks) may be adjusted to once daily.
- A once-daily 25 mg/kg ceftazidime dose is effective when combined with twice-daily amoxicillin for empirical septicemia treatment.
- This adjustment can simplify treatment regimens for preterm neonates.
Abstract:
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.