Are We Dosing Correctly? Population Pharmacokinetics of Piperacillin in Critically Ill Pediatric Patients

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ID: 327266
2026
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Abstract
Abstract Background Dosing guidelines of piperacillin are well defined in healthy pediatric and adult populations but have not been extensively studied in critically ill pediatric patients who often have significant alterations in antibiotic pharmacokinetics (PK) and pharmacodynamics (PD). Since critically ill pediatric patients are likely to receive multiple courses of antimicrobials, optimization of drug dosing and delivery is critically important for individual patient outcomes. This study will test the hypothesis that the PK of piperacillin is substantially altered in critically ill pediatric patients. Methods We prospectively enrolled patients in VUMC pediatric ICUs receiving piperacillin. Plasma samples were collected at opportune timepoints. Piperacillin plasma concentrations were measured by LC-MS/MS. Monolix was used to fit population PK models using one and two-compartment models with a proportional error model. Covariate modeling was performed with a priori selected covariates: ECMO, CRRT, sex, race, ethnicity, gestational age, and creatinine clearance (CrCl). The final covariate model was used to perform probability of target attainment (PTA) analysis using Monte Carlo simulation, including 3 weight categories and 2 CrCl categories. PTA was calculated over a grid of possible MIC values based on three targets, 65% fT>MIC, 100% fT>MIC, and 100% fT>4×MIC. Results Data from 19 pediatric participants receiving piperacillin were analyzed. An average of 3 samples were collected per participant. A one compartment with proportional error model was selected as the base model. Population PK parameter estimates for the base model, base model with weight, and final covariate model were calculated. Individual inclusion of creatinine clearance, race, and ethnicity significantly improved the model fit, but their inclusion in the model did not provide evidence of being significantly better than the model with only weight and CrCl. The results from the PTA analysis are seen in Figure 1. We observed an overall ordering of PTA by dosing regimen across all three targets, with continuous and 4-hour infusions having the highest PTA and 30-minute infusions having the lowest PTA. Increased CrCl led to reduced PTA and as weight increased, PTA also increased. Conclusion This study will be among the first to characterize piperacillin PK in the critically ill pediatric population. Given the variability observed in this population, clinicians should incorporate popPK models into their local antibiograms to determine optimal dosing. The use of extended infusions may be beneficial for PK/PD target achievement, particularly for resistant pathogens. Since clinical covariates affect PK parameters, this population may also benefit from therapeutic drug monitoring.
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Authors Stephanie Rolsma, Marisa Blackman, Cole Beck, Ahmad Dbouk, Foday Morovia, Faith Glover, Gabriella Ess, Katelyn Dohler, Brian Bridges, Leena Choi, C Buddy Creech, Mph
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Journal journal of the pediatric infectious diseases society
Year 2026
DOI
10.1093/jpids/piag070/piag070.001
URL
https://academic.oup.com/jpids/article-pdf/15/Supplement_2/S1/70833113/piag070.001.pdf
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