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Assistant Clinical Professor, Pharmacy Practice, University of Connecticut School of Pharmacy, Storrs, Connecticut, Clinical Pharmacist, Department of Pharmacy, Division of Infectious Disease, Connecticut Children's Medical Center, Hartford, Connecticut
Department Head, Perinatology, Hospital Maternidad Nuestra Señora de la Altagracia, Santo Domingo, Dominican Republic
Perinatologist, Hospital Maternidad Nuestra Señora de la Altagracia
Perinatologist, Hospital Maternidad Nuestra Señora de la Altagracia
Perinatologist, Hospital Maternidad Nuestra Señora de la Altagracia
Perinatologist, Hospital Maternidad Nuestra Señora de la Altagracia
Associate Professor of Pediatrics, Division of Infectious Diseases, University of Connecticut School of Medicine, Farmington, Connecticut, Connecticut Children's Medical Center, Department of Pediatrics Division of Infectious Diseases 282 Washington Street Hartford, Connecticut 06106 fax 860/545-9371 jsalaza{at}ccmckids.org
Published Online, April 10, 2007. www.theannals.com, DOI 10.1345/aph.1H585
With this in mind, we performed a pilot study to evaluate the cerebrospinal fluid (CSF) concentrations of cefepime in neonates with suspected bacterial meningitis during a nosocomial outbreak of resistant Klebsiella pneumoniae in a large neonatal intensive care unit in the Dominican Republic. The study was approved by the ethics committee at the Hospital Maternidad Nuestra Señora de la Altagracia in Santo Domingo, Dominican Republic.
Methods. Nine neonates with suspected bacterial meningitis, as demonstrated by CSF pleocytosis and abnormal protein and glucose, received intravenous cefepime 50 mg/kg every 12 hours. Serum and CSF samples were obtained at 48 hours (ie, the trough after the 4th dose). Cefepime concentrations were determined using a validated high-performance liquid chromatography assay2 at the Hartford Hospital Center for Anti-Infective Research and Development in Hartford, Connecticut. Statistical analysis was done using either an unpaired t-test or the Mann–Whitney rank sum test when appropriate. Values were considered significant if the p value was less than 0.05.
Discussion. Table 1 shows the demographics and cefepime concentrations obtained from 2 preterm and 7 full-term babies enrolled in the study. All neonates received the first dose by 72 hours of life. No statistically significant differences in mean serum cefepime trough concentrations were seen between groups (full-term 32.2 µg/mL vs preterm 35.3 µg/mL; t-test p = 0.86). Trough serum concentrations were consistent with those reported in a similar population by Capparelli et al.3 Because of these high serum concentrations and the potential for toxicity, the currently recommended dose of cefepime for this age group is now 30 mg/kg every 8 hours.3,4
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Table 1 also shows that CSF trough concentrations were lower in the 7 full-term neonates (median 2.59 µg/mL) than in the 2 preterm neonates (median 18.6 µg/mL). Despite the small sample size, the differences in CSF concentrations were close to achieving statistical significance (Mann–Whitney U test p = 0.056). Although the dose used in our patients is slightly higher than the currently recommended dose, it is very likely that the CSF concentrations in preterm babies will still be higher even at the lower dose.
Our study provides preliminary data indicating that cefepime concentrations in the CSF of premature neonates may be higher than those seen in full-term neonates. These differences, similar to those noted with other antibiotics, are very likely due to the relative immaturity of the blood–brain barrier in premature neonates.5 None of the neonates had allergic reactions and all 9 babies survived and were doing well at follow-up. These results should be confirmed in a larger study designed and statistically powered to compare CSF concentrations in full-term and preterm neonates with meningitis.
Footnotes
Cefepime was provided to Dr. Rivera through an unrestricted research grant from Bristol-Myers Squibb, Puerto Rico. Bristol-Myers Squibb was not involved in the study design, laboratory studies, data analysis, or manuscript preparation. Dr. Salazar has been a consultant and speaker for Bristol-Myers Squibb, Latin America.
The data were presented in part as a poster at the joint meeting of the Pediatric Academic Society and the Society for Pediatric Research, San Francisco, California, May 2004. This information is available in abstract form (abstract 233) in the April 2004 Pediatric Research Supplement.
References
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