Vancomycin Population Pharmacokinetics in Critically Ill Adults During Sustained Low-Efficiency Dialysis.
Acute Kidney Injury
/ drug therapy
Aged
Aged, 80 and over
Anti-Bacterial Agents
/ administration & dosage
Chromatography, Liquid
/ methods
Critical Illness
/ therapy
Female
Humans
Hybrid Renal Replacement Therapy
/ adverse effects
Male
Mass Spectrometry
/ methods
Microbial Sensitivity Tests
/ statistics & numerical data
Middle Aged
Monte Carlo Method
Prospective Studies
Serum Albumin
/ analysis
Vancomycin
/ administration & dosage
Journal
Clinical pharmacokinetics
ISSN: 1179-1926
Titre abrégé: Clin Pharmacokinet
Pays: Switzerland
ID NLM: 7606849
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
pubmed:
1
9
2019
medline:
27
5
2021
entrez:
1
9
2019
Statut:
ppublish
Résumé
Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking. The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies. Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses. From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.
Sections du résumé
BACKGROUND
Sustained low-efficiency dialysis (SLED) is a hybrid form of dialysis that is increasingly used in critically ill patients with kidney injury and hemodynamic instability. Antimicrobial dosing for patients receiving SLED is informed by pharmacokinetic studies that describe the drug clearance. Studies available to assist in the dosing of vancomycin in the context of SLED are lacking.
OBJECTIVE
The objective of this prospective observational study was to describe the population pharmacokinetics of vancomycin in critically ill patients receiving SLED, and use simulation studies to propose dosing strategies.
METHODS
Serial serum samples were obtained from 31 critically ill patients prescribed vancomycin while receiving SLED. Vancomycin concentrations were quantified in plasma using a validated liquid chromatography mass spectrometry/mass spectrometry method. A population pharmacokinetic model was developed, and Monte Carlo simulation was used to determine the probability of target attainment at different doses.
RESULTS
From a total of 335 serum samples from 31 patients receiving 52 sessions of SLED therapy, a two-compartment linear model with zero-order input was developed. The mean (standard deviation) clearance of vancomycin on and off SLED was 5.97 (4.04) and 2.40 (1.46) L/h, respectively. Using pharmacodynamic targets for efficacy (area under the concentration-time curve from time zero to 24 h [AUC
CONCLUSIONS
In critically ill patients receiving SLED, vancomycin clearance is highly variable with a narrow therapeutic window. Empiric dosing is proposed but subsequent dosing should be guided by drug levels.
Identifiants
pubmed: 31471789
doi: 10.1007/s40262-019-00817-6
pii: 10.1007/s40262-019-00817-6
doi:
Substances chimiques
Anti-Bacterial Agents
0
Serum Albumin
0
Vancomycin
6Q205EH1VU
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
327-334Références
Intensive Care Med. 2009 May;35(5):871-81
pubmed: 19066848
Crit Care Med. 2009 Mar;37(3):840-51; quiz 859
pubmed: 19237886
J Pharmacokinet Pharmacodyn. 2013 Apr;40(2):189-99
pubmed: 23404393
Ther Drug Monit. 2012 Aug;34(4):467-76
pubmed: 22722776
Chemotherapy. 2012;58(4):308-12
pubmed: 23147106
Am J Kidney Dis. 2015 Aug;66(2):322-30
pubmed: 25843704
Nephron Clin Pract. 2009;112(4):c222-9
pubmed: 19546581
Crit Care Med. 2006 Jan;34(1):51-6
pubmed: 16374156
Crit Care Med. 2011 Mar;39(3):560-70
pubmed: 21221000
Clin Nephrol. 2009 Oct;72(4):286-91
pubmed: 19825334
Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S35-9
pubmed: 16323118
Kidney Int. 2006 Sep;70(5):963-8
pubmed: 16850023
Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98
pubmed: 19106348
Crit Care Med. 2011 Mar;39(3):602-3
pubmed: 21330868
JAMA. 2005 Aug 17;294(7):813-8
pubmed: 16106006
Crit Care. 2011 Jan 28;15(1):204
pubmed: 21345275
Nephrol Dial Transplant. 2006 Mar;21(3):690-6
pubmed: 16326743
J Antimicrob Chemother. 2014 May;69(5):1416-23
pubmed: 24443514
J Antimicrob Chemother. 2011 Feb;66(2):227-31
pubmed: 21118912
Crit Care Med. 2014 Jul;42(7):1640-50
pubmed: 24674926
J Pharmacokinet Pharmacodyn. 2006 Jun;33(3):345-67
pubmed: 16284919
Crit Care. 2007;11(3):R68
pubmed: 17588270
Int J Pharm Pract. 2013 Feb;21(1):55-61
pubmed: 23301534
Crit Care Med. 2010 May;38(5):1360-9
pubmed: 20308884
Antimicrob Agents Chemother. 2013 Apr;57(4):1654-63
pubmed: 23335735
Nephrology (Carlton). 2017 May;22(5):343-353
pubmed: 28128881
Crit Care Res Pract. 2013;2013:479730
pubmed: 23573420
Diagn Microbiol Infect Dis. 2015 May;82(1):92-103
pubmed: 25698632