Format

Send to

Choose Destination
J Antimicrob Chemother. 2019 Jan 1;74(1):130-134. doi: 10.1093/jac/dky371.

Optimizing vancomycin dosage regimens in relation to high-flux haemodialysis.

Author information

1
Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia.
2
d3 Medicine, A Certara Company, Parsippany, NJ, USA.
3
Department of Pharmacy, Royal Melbourne Hospital, Parkville, VIC, Australia.
4
Department of Nephrology, Western Health, St Albans, VIC, Australia.
5
Western Health Chronic Disease Alliance, Western Centre for Health Research and Education, Western Health, St Albans, VIC, Australia.
6
Department of Medicine, University of Melbourne, St Albans, VIC, Australia.
7
National Centre for Antimicrobial Stewardship, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
8
Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
9
Department of Nephrology, Royal Melbourne Hospital, Parkville, VIC, Australia.
10
Department of Clinical Trials and Medical Innovation, Epworth Health, Richmond, VIC, Australia.

Abstract

Objectives:

To develop a population pharmacokinetic (PK) model for vancomycin in adults receiving high-flux haemodialysis (HFHD) in an effort to optimize vancomycin dosing in this population.

Methods:

A population PK model using NONMEM was developed using retrospective data collected from 48 vancomycin courses administered to patients (n = 37) receiving HFHD. Fixed-dose [1.5 g loading dose (LD), 1 g maintenance dose (MD)], literature-adapted weight-based (WBL; 20 mg/kg LD, 10 mg/kg MD) and hospital-adapted weight-based (WBH; 25-30 mg/kg LD, 20-25 mg/kg MD) dosage regimens were then simulated using the Monte Carlo method. The PTA was an AUC24/MIC ≥400 with success being a PTA ≥90%.

Results:

The data were best described using a two-compartment model. It was observed that fixed-dose and WBL dosage regimens resulted in a PTA ≤90% for most days. The WBH dosing achieved a PTA ≥90% on most days, but there were supratherapeutic concentrations with repeated dosing of vancomycin. If HFHD was delayed by 48-72 h after the LD, the PTA would fall below 90%. A dose-optimized regimen was developed: 30 mg/kg LD and 10 mg/kg MD given on HFHD days. An additional dose of 500 mg or 1 g was administered 24 h after the LD if HFHD occurred 48-72 h post-LD. This dose-optimized regimen afforded a PTA ≥90% on all days of therapy and achieved clinically acceptable pre-haemodialysis concentrations.

Conclusions:

Current vancomycin dosage regimens used clinically do not achieve a PTA ≥90% for most days of therapy for people receiving HFHD. A dose-optimized regimen was developed, which could be implemented in clinical practice.

PMID:
30215721
DOI:
10.1093/jac/dky371

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center