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


CONCLUSIONS
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. .
Kuti
Joseph L
JL
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06102-5037, USA.
Nicolau
David P
DP
D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006440:Hemofiltration; D006801:Humans; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008962:Models, Theoretical; D009010:Monte Carlo Method; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology
D013845:Thienamycins; D000077731:Meropenem