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Intraperitoneal vancomycin for peritoneal dialysis-associated peritonitis in children: Evaluation of loading dose
Kathleen Hennessy1, Edmund V Capparelli1,2, Gale Romanowski3
1Skaggs School of Pharmacy and Pharmaceutical Sciences, 8784University of California San Diego, La Jolla, CA, USA.
Insights
Current pediatric guidelines for vancomycin dosing in peritoneal dialysis (PD)-associated peritonitis may lead to excessively high drug levels in children. A reduced intraperitoneal (IP) vancomycin loading dose of 500 mg/L appears more appropriate and warrants further investigation.
Area of Science:
- Pediatric Nephrology
- Pharmacokinetics
- Infectious Diseases
Background:
- Current pediatric guidelines recommend intraperitoneal (IP) vancomycin dosing of 1000 mg/L for peritoneal dialysis (PD)-associated peritonitis, based on adult data.
- This dosing strategy may result in supra-therapeutic vancomycin exposure in pediatric patients due to differences in dialysate volume normalization.
- High vancomycin levels can potentially lead to adverse effects in children.
Purpose of the Study:
- To evaluate if the current 1000 mg/L IP vancomycin loading dose causes elevated drug levels in pediatric patients undergoing PD.
- To develop PK modeling-based dosing recommendations for vancomycin in pediatric PD-associated peritonitis.
Main Methods:
- Retrospective analysis of vancomycin levels from pediatric patients treated with IP vancomycin for PD-associated peritonitis.
- Population pharmacokinetic (PK) modeling using NONMEM to estimate vancomycin PK parameters and peak levels.
- Simulation of vancomycin peaks in virtual pediatric patients (3-70 kg) under various dosing scenarios.
Main Results:
- Analysis of six peritonitis episodes in three patients revealed high vancomycin levels with the 1000 mg/L loading dose (e.g., 95.6 ug/mL at 3h post-dose).
- Lower vancomycin levels were observed with a 500 mg/L loading dose (e.g., 33.2 ug/mL at 11h post-dose).
- PK modeling indicated that 1000 mg/L loading dose results in peaks >50 mg/L in patients <35 kg and >60 mg/L in patients <15 kg, with levels remaining >20 mg/L for over 2 days.
Conclusions:
- The current 1000 mg/L IP vancomycin loading dose is associated with higher-than-desired vancomycin levels in pediatric patients.
- A reduced loading dose of 500 mg/L is suggested as a potentially more appropriate alternative.
- Further studies are needed to validate the efficacy and safety of the 500 mg/L vancomycin loading dose.
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.
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