Journal article
Optimizing Vancomycin Dosing and Monitoring in Neonates and Infants Using Population Pharmacokinetic Modeling
Antimicrobial agents and chemotherapy, Vol.66(4), pp.e0189921-e0189921
04/19/2022
DOI: 10.1128/aac.01899-21
PMCID: PMC9046768
PMID: 35293782
Abstract
We determined optimal vancomycin starting dose regimens in infants ≤180 days of age to achieve the highest probability of target attainment with an area under the concentration-time curve for 24 h (AUC
) of ≥400 using population pharmacokinetic (PK) modeling. Secondarily, determination of the relationship between serum creatinine (SCR) and vancomycin clearance in neonates was done. A retrospective population PK study was designed and included pediatric patients ≤180 days old who had received vancomycin and had a serum vancomycin concentration sampled. A population PK model was developed using Pumas (v1.0.5). Simulation was performed with various dosing regimens to evaluate the probability of AUC
target attainment and probability of trough of ≤20 mg/liter, and comparison to published models was performed. Individual clearance estimates, obtained from the final model, were plotted against SCR and faceted by age quartiles to assess the relationship between SCR and vancomycin clearance. A total of 934 patients were included in the study (58.6% male; median age, 43.6 days [range of 0 to 184]; median number of concentration samples, 1 [range of 1 to 29]). A one-compartment model was developed with body weight (WT), SCR, and postmenstrual age (PMA) identified as significant covariates on clearance. Plotting vancomycin clearance versus SCR demonstrated no clear relationship between the two at <10 days postnatal age (PNA). Dosing regimens to attain AUC
and trough targets were stratified according to SCR for ≥10 days PNA and PMA for <10 days PNA. A vancomycin population PK model was developed for pediatric patients <180 days of age incorporating WT, SCR, and PMA. The relationship between vancomycin clearance and serum creatinine is not clear at <10 days PNA.
Details
- Title: Subtitle
- Optimizing Vancomycin Dosing and Monitoring in Neonates and Infants Using Population Pharmacokinetic Modeling
- Creators
- Praneeth Jarugula - University of Maryland, BaltimoreAyse Akcan-Arikan - Baylor College of MedicineFlor Munoz-Rivas - Baylor College of MedicineBrady S Moffett - Texas Children's HospitalVijay Ivaturi - University of Maryland, BaltimoreDanielle Rios - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.66(4), pp.e0189921-e0189921
- DOI
- 10.1128/aac.01899-21
- PMID
- 35293782
- PMCID
- PMC9046768
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Grant note
- T32 HD087969 / NICHD NIH HHS T32HD087969 / HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Language
- English
- Date published
- 04/19/2022
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9984353933002771
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