@article{ScharfWeineltSchroederetal.2022,
  author    = {Scharf, Christina and Weinelt, Ferdinand Anton and Schroeder, Ines and Paal, Michael and Weigand, Michael and Zoller, Michael and Irlbeck, Michael and Kloft, Charlotte and Briegel, Josef and Liebchen, Uwe},
  title     = {Does the cytokine adsorber CytoSorb (R) reduce vancomycin exposure in critically ill patients with sepsis or septic shock?},
  series = {Annals of intensive care},
  volume    = {12},
  journal   = {Annals of intensive care},
  number    = {1},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {2110-5820},
  doi       = {10.1186/s13613-022-01017-5},
  pages     = {8},
  year      = {2022},
  abstract  = {Background: Hemadsorption of cytokines is used in critically ill patients with sepsis or septic shock. Concerns have been raised that the cytokine adsorber CytoSorb (R) unintentionally adsorbs vancomycin. This study aimed to quantify vancomycin elimination by CytoSorb (R) . Methods: Critically ill patients with sepsis or septic shock receiving continuous renal replacement therapy and CytoSorb (R) treatment during a prospective observational study were included in the analysis. Vancomycin pharmacokinetics was characterized using population pharmacokinetic modeling. Adsorption of vancomycin by the CytoSorb (R) was investigated as linear or saturable process. The final model was used to derive dosing recommendations based on stochastic simulations. Results: 20 CytoSorb (R) treatments in 7 patients (160 serum samples/24 during CytoSorb (R)-treatment, all continuous infusion) were included in the study. A classical one-compartment model, including effluent flow rate of the continuous hemodialysis as linear covariate on clearance, best described the measured concentrations (without CytoSorb (R)). Significant adsorption with a linear decrease during CytoSorb (R) treatment was identified (p <0.0001) and revealed a maximum increase in vancomycin clearance of 291\% (initially after CytoSorb (R) installation) and a maximum adsorption capacity of 572 mg. For a representative patient of our cohort a reduction of the area under the curve (AUC) by 93 mg/L*24 h during CytoSorb (R) treatment was observed. The additional administration of 500 mg vancomycin over 2 h during CytoSorb (R) attenuated the effect and revealed a negligible reduction of the AUC by 4 mg/L*24h. Conclusion: We recommend the infusion of 500 mg vancomycin over 2 h during CytoSorb (R) treatment to avoid subtherapeutic concentrations.},
  language  = {en}
}
@article{LiebchenWeineltScharfetal.2022,
  author    = {Liebchen, Uwe and Weinelt, Ferdinand and Scharf, Christina and Schr{\"o}der, Ines and Paal, Michael and Zoller, Michael and Kloft, Charlotte and Jung, Jette and Michelet, Robin},
  title     = {Combination of pharmacokinetic and pathogen susceptibility information to optimize meropenem treatment of Gram-negative infections in critically iII patients},
  series = {Antimicrobial Agents and Chemotherapy},
  volume    = {66},
  journal   = {Antimicrobial Agents and Chemotherapy},
  number    = {2},
  publisher = {American Society for Microbiology},
  address   = {Washington},
  issn      = {0066-4804},
  doi       = {10.1128/aac.01831-21},
  pages     = {12},
  year      = {2022},
  abstract  = {Meropenem is one of the most frequently used antibiotics to treat life-threatening infections in critically ill patients. This study aimed to develop a meropenem dosing algorithm for the treatment of Gram-negative infections based on intensive care unit (ICU)-specific resistance data. Antimicrobial susceptibility testing of Gram-negative bacteria obtained from critically ill patients was carried out from 2016 to 2020 at a tertiary care hospital. Based on the observed MIC distribution, stochastic simulations (n = 1,000) of an evaluated pharmacokinetic meropenem model, and a defined pharmacokinetic/pharmacodynamic target (100\%T->4xMIC while minimum concentrations were <44.5 mg/L), dosing recommendations for patients with varying renal function were derived. Pathogen-specific MIC distributions were used to calculate the cumulative fraction of response (CFR), and the overall MIC distribution was used to calculate the local pathogen-independent mean fraction of response (LPIFR) for the investigated dosing regimens. A CFR/LPIFR of >90\% was considered adequate. The observed MIC distribution significantly differed from the EUCAST database. Based on the 6,520 MIC values included, a three-level dosing algorithm was developed. If the pathogen causing the infection is unknown (level 1), known (level 2), known to be neither Pseudomonas aeruginosa nor Acinetobacrer baumannii, or classified as susceptible (level 3), a continuous infusion of 1.5 g daily reached sufficient target attainment independent of renal function. In all other cases, dosing needs to be adjusted based on renal function. ICU-specific susceptibility data should be assessed regularly and integrated into dosing decisions. The presented workflow may serve as a blueprint for other antimicrobial settings.},
  language  = {en}
}