Klin Farmakol Farm. 2011;25(3):116-121

Dosage of vancomycin during continuous renal replacement therapy

Jana Zahálková^1,2, Jan Strojil³, Naděžda Petejová⁴, Karel Urbánek³, Milan Grundmann⁵, Ivana Kacířová⁵

¹ III. interní klinika LF UP a FN Olomouc

² Hemodialyzační oddělení nemocnice Šternberk, Středomoravská nemocniční a.s.

³ Ústav farmakologie LF UP a FN Olomouc

⁴ Interní klinika FN a LF OU Ostrava

⁵ Oddělení klinické farmakologie FN a LF OU Ostrava

The aim of the study: To analyze the influence of continuous venovenous hemofiltration (CVVH) on efficacy of vancomycin dosage in

critically ill septic patients (pts). Using pharmacokinetic modelling we tried to find an individual dosing regimen for the first day and to

optimize pts´ chance of achieving sufficient AUC/MIC90 values.

Method: We investigated 15 septic pts with acute renal injury on CVVH,

who were treated with vancomycin either 1.0 g every 12 hours (stage I – injury, n = 9) or 1.0 every 24 hours (stage F – failure, n = 6).

CVVH was performed with high-flux polysulfone membrane, filtration rate 45 ml/kg b.w./h. and pre- postdilution mode of substitution

(50 %/50 %). Using serum vancomycin concentration measurements at hour 1., 6. and at the end of dosing interval, we analyzed the

achieved AUCs in relationship to MIC90 of identified causative pathogens. Pharmacokinetic modelling in MW Pharm 4.0 was performed.

Two boosted dosing regimens were modelled: shortening the dosing interval and increasing the first loading dose.

Results: Only 4 pts

(27 %) maintained trough levels above the recommended minimum of 10 mg/l at the end of the first day (1 stage I, 3 stage F), however,

12 of 15 (80 %) pts achieved sufficient AUC/MIC90 ≥ 400 for their identified pathogen. Stage F pts were more likely to reach trough levels

(50 % vs. 11 %) and AUC/MIC90 (100 % vs. 67 %). When an MIC90 of 1.0 mg/l was considered, only 4 pts (27 %) would achieve effective AUC/

MIC90 on the first day. For MIC90 of ≥ 2.0 mg/l, none of the pts would attain sufficient AUC/MIC90. Shortening the dosing interval from 12

to 8 hours and from 24 to 12 hours increased chances of achieving sufficient AUC/MIC90 from 27 % to 87 % for MIC90 of 1.0 mg/l. Increasing

the loading dose by an extra 0.5 g had the same effect. Neither boosted dosing was sufficient for MIC90 ≥ 2.0 mg/l in any of the pts.

Conclusions: Current vancomycin dosing recommendations for critically ill patients on CVVH fail to achieve target trough levels on Day

1. The resulting AUC/MIC90 is sufficient only for pathogens with low MIC90. Boosted loading dose can increase efficacy for MIC90 = 1.0

but fails if it is ≥ 2.0 mg/l. More aggressive loading doses should be used in critically ill septic patients on CVVH to achieve adequate

therapeutic exposure during this critical time period.

Keywords: vancomycin, therapeutic drug monitoring, sepsis, acute kidney injury, continuous renal replacement therapy

Published: December 1, 2011  Show citation