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. 2023 Sep 14;24(1):270.
doi: 10.1186/s12882-023-03314-y.

Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation

Susan J Lewis  1   2 , Soo Min Jang  3 , Bruce A Mueller  4
Affiliations

Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation

Susan J Lewis et al. BMC Nephrol. .

Abstract

Background: Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen.

Methods: Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses.

Results: HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets.

Conclusions: Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.

Keywords: Daptomycin; Home hemodialysis; Monte Carlo simulation; Pharmacodynamics; Pharmacokinetics; Renal disease; Vancomycin.

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Conflict of interest statement

Dr. Mueller received grant funding from NxStage/Fresenius Medical Care AG & Co. to support this study. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Simulated Home Hemodialysis Schedules
Fig. 2
Fig. 2
One Week of Predicted AUC24h IQR with Model-recommended Daptomycin Regimens in Ten Home Hemodialysis Settings
Fig. 3
Fig. 3
Frequency of Mean Vancomycin AUC24h Before and After Virtual TDM
See this image and copyright information in PMC

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