Cefazolin pharmacokinetics in premature infants

• Published in: Journal of perinatology 2019-09, Vol.39 (9), p.1213-1218
• Main Authors: Balevic, Stephen J., Smith, P. Brian, Testoni, Daniela, Wu, Huali, Brouwer, Kim L. R., Zimmerman, Kanecia O., Rivera-Chaparro, Nazario D., Benjamin, Daniel K., Cohen-Wolkowiez, Michael
• Format: Article
• Language: English
• Subjects: 692/700/1720; 692/700/565/1436/2774; Age; Analysis; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics; Bayesian analysis; Cefazolin; Cefazolin - administration & dosage; Cefazolin - pharmacokinetics; Computer simulation; Creatinine; Datasets as Topic; Dosage; Dosage and administration; Drug dosages; Drug therapy; Female; Gestation; Gestational Age; Health care facilities; Humans; Infant, Newborn; Infant, Premature - blood; Infant, Premature - metabolism; Infants; Infants (Premature); Intravenous administration; Male; Medicine; Medicine & Public Health; Methicillin; Models, Biological; Monte Carlo simulation; Nonlinear analysis; Pediatric Surgery; Pediatrics; Pharmacokinetics; Pharmacology; Population; Premature babies; Premature birth; Prospective Studies
• ISSN: 0743-8346; 1476-5543; 1476-5543
• DOI: 10.1038/s41372-019-0368-z

Objective Pharmacokinetic (PK) data to guide cefazolin dosing in premature infants are virtually non-existent. Therefore, we aimed to characterize cefazolin PK in infants aged ≤32 weeks of gestation at birth. Study Design We conducted a prospective, open-label PK and safety study of cefazolin in infants ≤32 weeks gestation from a University Medical Center. We administered intravenous cefazolin and collected both timed and scavenged blood samples. We analyzed data using non-linear mixed effect modeling and simulated several dosage regimens to achieve target concentrations against methicillin-susceptible Staphylococcus aureus . Results We analyzed 40 samples from nine infants and observed that premature infants had lower clearance and greater volume of distribution for cefazolin compared to older children. The median (range) individual Bayesian estimates were 0.03 L/h/kg (0.01–0.08) for clearance and 0.39 L/kg (0.31–0.52) for volume. Conclusion Simulations suggested reduced cefazolin dosing based on postmenstrual age achieve target concentrations and potentially reduce unnecessary exposure.