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Wednesday, 05/28/2014 11:38:58 AM

Wednesday, May 28, 2014 11:38:58 AM

Post# of 27409
Interesting poster about Cytosorb clearing antibiotics at the Barcelona ESCMID conference 2 weeks ago
P1689
Poster Session VI
PK/PD of antifungals and miscellaneous antibacterials
COMPLETE IN-VITRO ADSORPTION OF ANTI-INFECTIVE DRUGS TO AN EXTRACORPOREAL
CYTOKINE FILTER
C. Kˆnig1, A.C. Rˆhr2, O.R. Frey2, A. Kˆberer3, A. Nierhaus4, C. Langebrake1, S. Kluge4, A. Brinkmann3
1Department of Pharmacy, University Hospital Hamburg-Eppendorf, Hamburg, Germany ; 2Department
of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany ; 3Department of Anaesthesia
and Intensive Care Medicine, General Hospital of Heidenheim, Heidenheim, Germany ; 4Department of
Intensive Care, University Hospital Hamburg-Eppendorf, Hamburg, Germany
Objectives: The purpose of the presented study was to examine the adsorptive capacity of a novel
extracorporeal cytokine filter with respect to the elimination of anti-infective drugs in an experimental invitro
set-up.
Methods:To investigate the filtrability of ceftazidime (80 mg/l), ciprofloxacin (15 mg/l), flucloxacillin (80
mg/l), fluconazole (40 mg/l), gentamicin (20 mg/l), linezolid (20 mg/l), meropenem (20 mg/l),
metronidazole (20 mg/l), piperacillin (80 mg/l), vancomycin (40 mg/l), voriconazole (10 mg/l) in NaCl 0,9
%, 1000 ml an extracorporeal cytokine filter (CytoSorb®, CytoSorbents) and a saline drip (Infusomat
space®, B.Braun) in circuit were used. Prior to sampling, 300 ml of solution were discarded to ensure
complete filling of the filter system. During a filtration time of 120 min. at a flow rate of 1,2 l/h samples of
the solution as well as post and pre- filter samples were retrieved and stored at -70 °C until analysis.
The quantification was performed by high performance liquid chromatography with UV-detection and
fluorescence polarization immunoassay.
Results: No drug was detectable in post filter samples at any time. Observed drug clearances were
(l/h): ceftazidime 1,27; ciprofloxacin 1,31; flucloxacillin 1,17; fluconazole 1,28; gentamicin 1,13; linezolid
1,26; meropenem 1,38; metronidazole 1,27; piperacillin 1,29; vancomycin 1,19; voriconazole 1,36.
Mean drug clearance was 1,26 ± 0,07 l/h and corresponded to the adjusted blood flow, mean half-life of
the examined substances was 23,10 ± 1,4 min. The decrease in concentration of the entire solution
followed first order kinetics.
Conclusion: In the presented in-vitro model, all tested substances were completely adsorbed by the
filter. Using a blood flow of 6 l/h, as it is standard during continuous renal replacement therapy in the
clinical setting and assuming a complete adsorption of the non-proteinbound fraction without saturation
effects at the binding sites, considerable elimination of antibiotics seems likely. For example, an
additional elimination of up to 1500 mg meropenem, 3000 mg ceftazidime or 4500 mg piperacillin may
occur. Further studies are needed to investigate the performance of the filter in the presence of blood
components regarding adsorption and possible saturation effects at the binding sites as well as to
quantify these effects to substantiate adequate dosing recommendations. In the meantime it appears
advisable to use maximum approved dosages e.g. meropenem 6g/24h, piperacilline 16g/24h or
ceftazidime 9g/24h in patients without renal failure. The application of therapeutic drug monitoring to
avoid the risk of treatment failure is highly recommended.
Tuesday - May 13, 2014
P1689
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