Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration

Bilgrami, I., Roberts, J. A., Wallis, S. C., Thomas, J., Davis, J., Fowler, S., Goldrick, P. B. and Lipman, J. (2010) Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration. Antimicrobial Agents and Chemotherapy, 54 7: 2974-2978. doi:10.1128/AAC.01582-09

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Author Bilgrami, I.
Roberts, J. A.
Wallis, S. C.
Thomas, J.
Davis, J.
Fowler, S.
Goldrick, P. B.
Lipman, J.
Title Meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2010-07
Sub-type Article (original research)
DOI 10.1128/AAC.01582-09
Open Access Status File (Publisher version)
Volume 54
Issue 7
Start page 2974
End page 2978
Total pages 5
Editor Louis B. Rice
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2011
Language eng
Formatted abstract
Use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (CVVHF) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. The objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume CVVHF with high-volume exchanges (≥4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] every 8 h) are sufficient for treatment of less susceptible organisms such as Burkholderia pseudomallei (MIC, 4 mg/liter); and, finally, to compare the clearances observed in this study with data from previous studies using lower-volume exchanges (1 to 2 liters/h). We recruited 10 eligible patients and collected serial pre- and postfilter blood samples and ultrafiltrate and urine samples. A noncompartmental method was used to determine meropenem pharmacokinetics. The cohort had a median age of 56.6 years, a median weight of 70 kg, and a median APACHE II (acute physiology and chronic health evaluation) score of 25. The median (interquartile range) values for meropenem were as follows: terminal elimination half-life, 4.3 h (2.9 to 6.0); terminal volume of distribution, 0.2 liters/kg (0.2 to 0.3); trough concentration, 7.7 mg/liter (6.2 to 12.9); total clearance, 6.0 liters/h (5.2 to 6.2); hemofiltration clearance, 3.5 liters/h (3.4 to 3.9). In comparing the meropenem clearance here with those in previous studies, ultrafiltration flow rate was found to be the parameter that accounted for the differences in clearance of meropenem (R2 = 0.89). In conclusion, high-volume CVVHF causes significant clearance of meropenem, necessitating steady-state doses of 1,000 mg every 8 h to maintain sufficient concentrations to treat less susceptible organisms such as B. pseudomallei
Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Keyword Acute-renal-failure
Intensive-care
Replacement therapy
Pharmacokinetics
Hemodiafiltration
Pharmacodynamics
Melioidosis
Antibiotics
Elimination
Drug
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Sun, 04 Jul 2010, 00:07:23 EST