Derivation of meropenem dosage in patients receiving continuous veno-venous hemofiltration based on pharmacodynamic target attainment.

Abstract:

BACKGROUND:Dosage recommendations for antibiotics in patients receiving continuous veno-venous hemofiltration (CVVH) should be based on pharmacodynamic requirements. For meropenem, this would be achieving appropriate time above the minimum inhibitory concentration (T > MIC). We employed Monte Carlo simulation to calculate the bactericidal target attainment for various dosing regimens of meropenem against Pseudomonas aeruginosa and Acinetobacter species. METHODS:Target attainment at 40% T > MIC was calculated for 5,000 simulated subjects receiving meropenem 1,000 mg every 12 and 8 h, and 500 mg every 12, 8 and 6 h. Pharmacokinetics were extrapolated from primary literature sources utilizing similar methods of CVVH. MIC data for P. aeruginosa and Acinetobacter species were derived from the US 2003 MYSTIC study. Target attainment at the breakpoint of 4 microg/ml was also calculated. RESULTS:Only regimens of 1,000 mg every 8 h and 500 mg every 6 h essentially achieve 100% target attainment at the breakpoint. However, due to higher peak concentrations, 1,000 mg every 8 h is able to attain improved target attainment against more resistant populations of P. aeruginosa and Acinetobacter species, thus providing the greatest probability of bactericidal exposure. CONCLUSION:Meropenem 1,000 mg every 8 h optimizes the pharmacodynamic profile in patients undergoing CVVH. Lower doses or increased dosing intervals should not be advocated for inpatients receiving this renal replacement technique. .

journal_name

Chemotherapy

journal_title

Chemotherapy

authors

Kuti JL,Nicolau DP

doi

10.1159/000086598

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

211-6

issue

4

eissn

0009-3157

issn

1421-9794

pii

86598

journal_volume

51

pub_type

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