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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, Joshua S., 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.

Document type: Journal Article
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IRMA ID 81704288xPUB43
NHMRC Grant No. 519702
Title Meropenem Dosing in Critically Ill Patients with Sepsis Receiving High-Volume Continuous Venovenous Hemofiltration
Author Bilgrami, I.
Roberts, J. A.
Wallis, S. C.
Thomas, J.
Davis, Joshua S.
Fowler, S.
Goldrick, P. B.
Lipman, J.
Journal Name Antimicrobial Agents and Chemotherapy
Publication Date 2010
Volume Number 54
Issue Number 7
ISSN 0066-4804   (check CDU catalogue open catalogue search in new window)
Start Page 2974
End Page 2978
Total Pages 4
Place of Publication Washington, United States
Publisher American Society for Microbiology
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.

DOI http://dx.doi.org/10.1128/AAC.01582-09   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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