ABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Cefazolin/pharmacokinetics , Infant, Premature/metabolism , Anti-Bacterial Agents/administration & dosage , Cefazolin/administration & dosage , Datasets as Topic , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature/blood , Male , Models, Biological , Prospective StudiesABSTRACT
Micafungin is used off-label in the United States to treat invasive candidiasis in neonates. We used an established pharmacokinetic model to determine micafungin exposures for 46 courses in 39 hospitalized infants. In this small cohort of infants, micafungin exposure was not associated with laboratory markers of liver toxicity, death or failure of microbiologic clearance.
Subject(s)
Antifungal Agents/pharmacokinetics , Electronic Health Records , Micafungin/pharmacokinetics , Antifungal Agents/therapeutic use , Candidiasis/drug therapy , Female , Hospitalization , Humans , Infant , Male , Micafungin/therapeutic useABSTRACT
Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.
