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Antimicrobial Agents and Chemotherapy, July 2005, p. 2760-2766, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2760-2766.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetics of Cefepime in the Neonate

Edmund Capparelli,^1* Christine Hochwald,² Maynard Rasmussen,^3,4 Amy Parham,² John Bradley,^3,4 and Fernando Moya^2,5

Pediatric Pharmacology Research Unit,¹ Department of Pediatrics, University of California, San Diego,⁴ Sharp Mary Birch Hospital for Women and Children, San Diego, California,³ Memorial Hermann Children's Hospital,² Department of Pediatrics, University of Texas Health Science Center, Houston, Texas⁵

Received 21 September 2004/ Returned for modification 6 December 2004/ Accepted 15 March 2005

Newborn infants cared for in neonatal intensive care units may develop nosocomial infections. Cefepime, a "fourth-generation" cephalosporin (i.e., with activity against virtually all of the chromosomal-beta-lactamase-producing and many extended-spectrum-beta-lactamase-producing organisms), provides excellent activity against many gram-negative pathogens resistant to expanded-spectrum cephalosporins currently used to treat neonatal infections. The purpose of this study was to determine the pharmacokinetics of cefepime in this population to optimize dosing and minimize potential adverse events. Premature and term infants <4 months of age hospitalized in two neonatal intensive care units were studied. Limited pharmacokinetic (PK) sampling occurred following a dose of cefepime at 50 mg/kg of body weight infused over 30 min. Population pharmacokinetic parameters were determined using the program NONMEM. Fifty-five infants were enrolled. Their average (± standard deviation) gestational age at birth was 30.5 ± 5.3 weeks, and their average postnatal age at PK evaluation was 14.5 ± 14.7 days. In the final PK model, cefepime clearance (CL) was strongly associated with serum creatinine (SCr) (CL [ml/min/kg] = 0.26 + 0.59/SCr). The volume of distribution for infants with a postconceptional age of <30 weeks was larger than that for infants with a postconceptional age of >30 weeks (0.51 versus 0.39 liter/kg, respectively). The Bayesian analysis-predicted cefepime trough concentration at a dose of 50 mg/kg every 12 h for infants 14 days of age was 29.9 ± 16.6 µg/ml. Cefepime, dosed at 30 mg/kg/dose every 12 h for infants less than 14 days of age, regardless of gestational age, should provide antibiotic exposure equivalent to or greater than 50 mg/kg every 8 h in older infants and children.

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* Corresponding author. Mailing address: UCSD Pediatric Pharmacology Research Unit, 4094 4th Avenue, Suite 201, San Diego, CA 92103. Phone: (619) 497-2100. Fax: (619) 497-2101. E-mail: ecapparelli{at}ucsd.edu.

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Antimicrobial Agents and Chemotherapy, July 2005, p. 2760-2766, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2760-2766.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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