Intraperitoneal vancomycin for peritoneal dialysis-associated peritonitis in children: Evaluation of loading dose guidelines

Abstract

Background: Current pediatric International Society for Peritoneal Dialysis guidelines for initial treatment of peritoneal dialysis (PD)-associated peritonitis suggest either monotherapy with cefepime or double therapy with first-generation cephalosporin or glycopeptide and ceftazidime or aminoglycoside. When using vancomycin, the intraperitoneal (IP) recommended pediatric loading dosage is 1000 mg/L of dialysate. This is based on adult pharmacokinetic (PK) studies and roughly translates to the adult recommendation where 30 mg/kg in 2 L is approximately 1000 mg/L. However, since the dialysate volume in pediatric patients is normalized to body surface area and not weight, the current recommended dosing can result in high vancomycin exposure in children. Vancomycin can potentially cause adverse effects. We aimed to determine if the IP vancomycin dosing of 1000 mg/L was causing elevated vancomycin levels and to offer possible dosing recommendations based on PK modeling and simulation. Methods: Retrospective review of pediatric patients who had been treated with IP vancomycin for PD-associated peritonitis. Vancomycin levels obtained for clinical monitoring were analyzed using NONMEM to generate population and individual (empiric Bayesian) estimates of vancomycin PK parameters and estimated peak levels. Predicted vancomycin peaks were also simulated from virtual pediatrics patients 3–70 kg following various dosing strategies. Results: Six episodes of peritonitis in three patients were analyzed. In the two episodes treated with 1000 mg/L, the first vancomycin levels (h post) were 95.6 ug/mL (3) and 49 (33) and following 500 mg/L were 33.2 (11), 30.2 (11), 23.6 (24), and 22.1 (11). All patients were cured of their peritonitis without the need for catheter removal. Based on our population PK model, a 1000 mg/L IP vancomycin loading dose will typically result in peak > 50 mg/L in patients weighing <35 kg and >60 mg/L in patients <15 kg. Vancomycin levels will remain above 20 mg/L for over 2 days without additional vancomycin dosing. Conclusion: The data suggest that a loading dose of vancomycin 1000 mg/L leads to higher than desired vancomycin levels and should be lowered. A 500 mg/L loading dosing appears more appropriate and needs further study.

Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring

“… Better prior probability was reported in a population PK model based on rich sampling (full data set: e.g., at the end of infusion, at 60, 120, and 300 min following the infusion, and immediately before the next dose) than that based on limited sampling (e.g., trough and peak concentrations) [ 66 , 67 , 68 , 69 , 70 , 71 ]. Population properties (i.e., age, body weight, kidney function, other potential covariates) for establishing a population PK model should be considered to determine the reasonable candidates for the MIPD software to increase the accuracy of dosing [ 53 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. The Bayesian prior information has been accumulated in special populations of obesity, paediatrics, and renal replacement therapy (RRT).…”

“…Population properties (i.e., age, body weight, kidney function, other potential covariates) for establishing a population PK model should be considered to determine the reasonable candidates for the MIPD software to increase the accuracy of dosing [ 53 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ].…”

Peritoneal dialysis in children: Reaching milestones but room for growth

“…Extrapolating adult PD research findings to the paediatric population may not always be appropriate. As an example, in this issue of PDI, Hennessy et al discuss dosing recommendations for the use of intraperitoneal vancomycin based on pharmacokinetic modelling, 9 pointing out that current dosing recommendations 10 that are based on adult practice may lead to toxic vancomycin levels among children.…”