Optimization of anti-infective dosing regimens during online haemodiafiltration

Jager, Nynke G L; Zandvliet, Anthe S.; Touw, Daan; Penne, E. Lars

doi:10.1093/ckj/sfx009

Cited by 10 publications

(18 citation statements)

References 46 publications

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“…The key requirements for an HDF programme and protocols for how to implement HDF at a sufficient dose are logical and not terribly difficult to implement and are described in detail elsewhere [ 42–44 ]. In a recent paper, dosing adjustments of anti-infectious agents were summarized [ 45 ]. Indeed, starting up an HDF programme may mean extra investments in machinery and in the training of personnel.…”

Section: Haemodiafiltration and Survivalmentioning

confidence: 99%

Clinical evidence on haemodiafiltration

Grooteman

Nubé

Bots

2018

Nephrology Dialysis Transplantation

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Haemodiafiltration (HDF) combines diffusive and convective solute removal in a single treatment session. HDF provides a greater removal of higher molecular weight uraemic retention solutes than conventional high-flux haemodialysis (HD). Recently completed randomized clinical trials suggest better patient survival with online HDF. The treatment is mainly used in Europe and Japan. This review gives a brief overview of the presently available evidence of the effects of HDF on clinical end points, it speculates on possible mechanisms of a beneficial effect of HDF as compared with standard HD and ends with some perspectives for the future.

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Section: Haemodiafiltration and Survivalmentioning

confidence: 99%

Clinical evidence on haemodiafiltration

Grooteman

Nubé

Bots

2018

Nephrology Dialysis Transplantation

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“…Some studies have focus in behavior of antibiotics with high‐flux intermittent hemodialysis. However, despite more frequent use of OL‐HDF in ESRD patients, few studies explain how this therapy affects the pharmacokinetic of antibiotics and specific dose adjustments .…”

Section: Discussionmentioning

confidence: 99%

Vancomycin hemodialysis: Clearance differences between high‐flux hemodialysis and on‐line hemodiafiltration

et al. 2018

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The aim of this study was to analyze the differences between vancomycin clearance (Kd) with high‐flux hemodialysis (HFHD) and on‐line hemodiafiltration (OL‐HDF). The OL‐HDF therapy combined the diffusion and convective transport of solutes. To compare the Kd, a vancomycin loading dose of 1 g was administered intravenously post‐dialysis to 11 chronic and anuric (<100 mL/24 h) hemodialysis patients, undergoing HFHD and post‐dilutional OL‐HDF in consecutive therapies. Additional doses of 0.5 g were administered after 45 minutes at the end of each dialysis therapy during antibiotic treatment. Blood samples were drawn from arterial and venous lines at the start of hemodialysis sessions and at the first, second, third, and fourth hours. Additional samples were drawn at 15, 30, and 45 minutes after the end of dialysis therapy. Vancomycin plasma concentration, blood urea nitrogen (BUN), creatinine, and β2‐microglobulin were measured. The patients’ hydration status was evaluated by bioimpedance analysis. The mean of vancomycin dialyzer clearance (Kddc) calculated was 110.8 ± 15 mL/min with HFHD and 146.8 ± 13.8 mL/min with OL‐HDF (P = 0.025). Significant differences were also obtained for β2‐microglobulin clearance, Kddc 72.6 ± 15.4 mL/min with HFHD and 113.4 ± 24.2 mL/min with OL‐HDF (P = 0.012), whereas no differences were found for BUN or creatinine. Additionally, to analyze differences between HFHD and OL‐HDF, a variable volume dual pool mathematical model was developed to estimate the body clearance (Kdbc), extraction mass (Me), and inter‐compartment mass‐transfer coefficient (K12) of each molecule. A higher vancomycin Kddc with OL‐HDF produced by convection improved removal of antibiotic; this can compromise achieving a therapeutic concentration target. We recommended evaluating increased loading doses of vancomycin and avoiding administration during OL‐HDF to assure adequate treatment.

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“…The efficacy of vancomycin is associated with the area under the serum concentration—time curve (AUC)[3]. Reviews suggests that the AUC divided by the Minimum Inhibitory Concentration (MIC) best correlates with a successful outcome[4].…”

Section: Introductionmentioning

confidence: 99%

“…Adequate AUC/MIC ratios are important to prevent selection of resistant organisms and to improve the efficacy[5]. Therapeutic Drug Monitoring (TDM) aiming at a target AUC 24h /MIC ≥400 mg*h/L is generally used for designing and optimizing dosing regimens in patients treated with vancomycin[3]. In clinical practice vancomycin is used up till a MIC of 1mg/L so clinicians aim at an AUC 24h ≥400 mg*h/L.…”

Section: Introductionmentioning

confidence: 99%

“…The vancomycin clearance of the dialyzer is substantial and was reported to vary between 9.6 and 130.7 ml/min for low- and high-flux hemodialysis patients[7]. A dialysis patient is also prone to altered pharmacokinetic parameters like distribution, metabolism and other elimination processes which underlines the use of serum concentrations to enable adequate therapy[3].…”

Section: Introductionmentioning

confidence: 99%

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Vancomycin pharmacokinetic model development in patients on intermittent online hemodiafiltration

et al. 2019

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Background Vancomycin is frequently used in hemodialysis (HD) and in hemodiafiltration (HDF) patients and is usually administered in the last 30 or 60 minutes of a dialysis session. Vancomycin pharmacokinetics are not well described in HDF patients. The aim of this study is to develop a population pharmacokinetic (PPK) model and dosing regimen for vancomycin in HDF patients and to evaluate its applicability in low-flux (LF-HD) patients. Methods Two-compartment PPK models were developed using data from HDF patients (n = 17), and was parameterized as follows: non-renal clearance (CLm), renal clearance as a fraction of creatinine clearance (fr), central volume of distribution (V1), intercompartmental clearance (CL12), peripheral volume of distribution (V2) and extracorporeal extraction ratio (Eec). We evaluated the final model in a cohort of LF-HD patients (n = 21). Dosing schemes were developed for a vancomycin 24-h AUC of 400 mg*h/L. Results Model parameters (± SD) were: CLm = 0.473 (0.271) L/h, fr = 0.1 (fixed value), V1 = 0.278 (0.092) L/kgLBMc, CL12 = 9.96 L/h (fixed value), V2 = 0.686 (0.335) L/kgLBMc and Eec = 0.212 (0.069). The model reliably predicted serum levels of vancomycin in both HDF and LF-HD patients during and between dialysis sessions. The median of the prediction error (MDPE) as a measure of bias is -0.7% (95% CI: -3.4%-1.7%) and the median of the absolute values of the prediction errors (MDAPE) as a measure of precision is 7.9% (95% CI: 6.0%-9.8%). In both HDF and LF-HD, the optimal vancomycin loading dose for a typical patient weighing 70 kg is 1700 mg when administered during the last 60 minutes of the hemodialysis session. Maintenance dose is 700 mg if administered during the last 30 or 60 minutes of the hemodialysis session. Conclusion The developed PPK model for HDF is also capable of predicting serum levels of vancomycin in patients on LF-HD. A dosing regimen was developed for the use of vancomycin in HDF and LF-HD.

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Optimization of anti-infective dosing regimens during online haemodiafiltration

Cited by 10 publications

References 46 publications

Clinical evidence on haemodiafiltration

Clinical evidence on haemodiafiltration

Vancomycin hemodialysis: Clearance differences between high‐flux hemodialysis and on‐line hemodiafiltration

Vancomycin pharmacokinetic model development in patients on intermittent online hemodiafiltration

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