Efficacy of Standard Piperacillin Dosing in Children on Continuous Kidney Replacement Therapy

Among critically ill children with acute kidney injury (AKI) receiving continuous kidney replacement therapy (CKRT), standard dosing of piperacillin did not provide adequate systemic exposure, however, prolonged and continuous infusions may be beneficial, according to results of a study in Clinical Microbiology and Infection.

Investigators sought to characterize the population pharmacokinetics (PK) of piperacillin among children (N=32) with AKI in the pediatric intensive care unit. Of these patients, 19 were and 13 were not receiving CKRT. The investigators constructed a two-compartment PK model using 429 piperacillin measurements, and the population approach was used to analyze plasma, prefilter, postfilter, effluent, and urine concentrations. Three routes of piperacillin elimination were assessed, including renal, nonrenal, and extracorporeal.

Among patients in the CKRT and nonCKRT groups, no statistically significant group differences were observed for age, weight, and height, and all patients received a 10-day course of piperacillin/tazobactam 100 mg/kg/8h. Patients in the CKRT group, however, received treatment every 12 hours following the fourth dose. The PK target attainment was the percentage of patients who achieved minimum inhibitory concentrations (MICs) above 4, 8, 16, and 32 mg/L for more than 9 days.

Analysis of covariates showed that body weight was significantly correlated with the volumetric distribution of both the central and peripheral compartments and nonrenal clearance (P < .01). No significant correlations, however, were observed for renal clearance (CL_R) or intercompartmental (distribution) clearance (P >.05). Among patients in the nonCKRT group, estimated glomerular filtration rate and height had a significant effect on CL_R (P <.01), and the surface area of the hemofilter was significantly correlated with clearance among those receiving CKRT (P <.01).

Among patients in the CKRT and nonCKRT groups, 7 (37%) and 7 (54%) achieved the PK target attainment, respectively. Of note, none of the patients achieved the target attainment for the entirety of the treatment course.

Analysis of alternative dosing schedules suggested that a continuous infusion of 200 and 300 mg/kg/24h among the CKRT and nonCKRT groups, respectively, would result in PK target attainment across all MICs assessed.

Study limitations included the single-center design, small sample size, and absence of an external validation cohort.

According to the investigators, “the population model developed in this study can be used to individualize dosing and maximize antibiotic efficacy, thus overcoming the significant proportion of underexposed critically ill children observed with the standard dosing schedules.”

Reference

Butragueño-Laiseca L, Marco-Ariño N, Troconiz IF, et al. Population pharmacokinetics of piperacillin in critically ill children including those undergoing continuous kidney replacement therapy. Clin Microbiol Infect. Published online April 4, 2022. doi: 10.1016/j.cmi.2022.03.031