Table of contentsP001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP effluxR. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. EllisP002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez GallegoP003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsisF. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. TuzunP004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopeniaR. Riff, O. Naamani, A. DouvdevaniP005 - Analysis of neutrophil by hyper spectral imaging - A preliminary reportR. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. ShimazuP006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgeryS. Ono, T. Kubo, S. Suda, T. Ueno, T. IkedaP007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational studyT. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. ShimazuP008 - Comparison of bacteremia and sepsis on sepsis related biomarkersT. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. OnoP009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purificationT. Taniguchi, M. OP010 - Validation of a new sensitive point of care device for rapid measurement of procalcitoninC. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. LottP011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive proteinM. M. Meili, P. S. SchuetzP012 - Do we need a lower procalcitonin cut off?H. Hawa, M. Sharshir, M. Aburageila, N. SalahuddinP013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteriaV. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. MichaloudisP014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiberA. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. ImaizumiP015 - Diagnostic usefullness of combination biomarkers on ICU admissionM. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-AlcantaraP016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patientsN. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. NeeP017 - Extracellular histone H3 levels are in...

Dosing of vancomycin is often guided by therapeutic drug monitoring and population pharmacokinetic models in the intensive care unit (ICU). The validity of these models is crucial, as ICU patients have marked pharmacokinetic variability. Therefore, we set out to evaluate the predictive performance of published population pharmacokinetic models of vancomycin in ICU patients. The PubMed database was used to search for population pharmacokinetic models of vancomycin in adult ICU patients. The identified models were evaluated in two independent data sets which were collected from two large hospitals in the Netherlands (Amsterdam UMC, Location VUmc, and OLVG Oost). We also tested a one-compartment model with fixed values for clearance and volume of distribution, in which a clinical standard dosage regimen (SDR) was mimicked to assess its predictive performance. Prediction error was calculated to assess the predictive performance of the models. Six models plus the SDR model were evaluated. The model of Roberts et al. (J. A. Roberts, F. S. Taccone, A. A. Udy, J.-L. Vincent, F. Jacobs, and J. Lipman, Antimicrob Agents Chemother 55:2704–2709, 2011, https://doi.org/10.1128/AAC.01708-10) performed satisfactorily, with mean and median values of prediction error of 5.1% and −7.5%, respectively, for Amsterdam UMC, Location VUmc, patients, and −12.6% and −17.2% respectively, for OLVG Oost patients. The other models, including the SDR model, yielded high mean values (−49.7% to 87.7%) and median values (−56.1% to 66.1%) for both populations. In conclusion, only the model of Roberts et al. was able to validly predict the concentrations of vancomycin for our data, whereas other models and standard dosing were largely inadequate. Extensive evaluation should precede the adoption of any model in clinical practice for ICU patients.

Use of an antibiotic checklist resulted in a significant increase in appropriateness of antibiotic use, but not in a reduction of LOS. Low overall checklist completion rates and discordance between checklist-answers and actual provided care might have attenuated the impact of the checklist.

Background Initial appropriate anti-infective therapy is associated with improved outcomes in patients with severe infections. In critically ill patients, altered pharmacokinetic (PK) behaviour is common and known to influence the achievement of PK/pharmacodynamic targets. Objectives To describe population PK and optimized dosing regimens for flucloxacillin in critically ill patients. Methods First, we developed a population PK model, estimated between-patient variability (BPV) and identified covariates that could explain BPV through non-linear mixed-effects analysis, using total and unbound concentrations obtained from 35 adult critically ill patients treated with intermittent flucloxacillin. Second, we validated the model using external datasets from two different countries. Finally, frequently prescribed dosing regimens were evaluated using Monte Carlo simulations. Results A two-compartment model with non-linear protein binding was developed and validated. BPV of the maximum binding capacity decreased from 42.2% to 30.4% and BPV of unbound clearance decreased from 88.1% to 71.6% upon inclusion of serum albumin concentrations and estimated glomerular filtration rate (eGFR; by CKD-EPI equation), respectively. PTA (target of 100%fT>MIC) was 91% for patients with eGFR of 33 mL/min and 1 g q6h, 87% for patients with eGFR of 96 mL/min and 2 g q4h and 71% for patients with eGFR of 153 mL/min and 2 g q4h. Conclusions For patients with high creatinine clearance who are infected with moderately susceptible pathogens, therapeutic drug monitoring is advised since there is a risk of underexposure to flucloxacillin. Due to the non-linear protein binding of flucloxacillin and the high prevalence of hypoalbuminaemia in critically ill patients, dose adjustments should be based on unbound concentrations.

This study suggests that a fixed dose of 1040 IU of F IX may be an effective way to rapidly counteract VKA therapy in our patient population and provides a basis for future research.

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Background: The pharmacokinetic (PK) data of ganciclovir (GCV), a first-line antiviral treatment for cytomegalovirus infections, in critically ill patients are limited. This study aimed at characterizing GCV population PK and interindividual variability (IIV) in intensive care unit (ICU) patients. Secondary objectives were to identify patient characteristics responsible for IIV and simulate GCV exposure for different dosing regimens. Method: In this retrospective observational study, clinical data and serum GCV levels were collected from ICU patients on intravenous GCV. PK modeling, covariate analyses, and explorative Monte Carlo dosing simulations (MCS) were performed using nonlinear mixed-effects modeling. Bootstrap and visual predictive checks were used to determine model adequacy. Results: In total, 128 GCV measurements were obtained from 34 patients. GCV PK conformed to a 1-compartment model with first-order elimination. After multivariate analyses, only the estimated glomerular filtration rate calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (P < 0.001) was included as a covariate. In the final model, the estimated clearance (CL) and volume of distribution (V1) were 2.3 L/h and 42 L, respectively, for a patient with the median CKD-EPI of the population (65 mL/min per 1.73 m2). The association between CKD-EPI and CL decreased the residual variability from 0.56 to 0.43 and V1-IIV from 114% to 80%, whereas CL-IIV changed from 43% to 47%. MCS revealed that a substantial number of patients may not achieve the GCV PK/pharmacodynamic target trough level (>1.5 mg/L) when administering the label-recommended dose reductions for patients with CKD-EPI <50 mL/min. Conclusions: A large IIV was observed in GCV PK among ICU patients. CKD-EPI could partially explain the IIV, although a large part of the variability remains unclear. MCS suggested that recommended dose reductions for CKD-EPI <50 mL/min may lead to subtherapeutic plasma GCV levels in these patients.

IntroductionHaemophilia A is an inherited bleeding disorder characterised by factor VIII (FVIII) deficiency. In patients with non-severe haemophilia A, surgery and bleeding are the main indications for treatment with FVIII concentrate. A recent study reported that standard dosing frequently results in FVIII levels (FVIII:C) below or above FVIII target ranges, leading to respectively a bleeding risk or excessive costs. In addition, FVIII concentrate treatment carries a risk of development of neutralising antibodies. An alternative is desmopressin, which releases endogenous FVIII and von Willebrand factor. In most patients with non-severe haemophilia A, desmopressin alone is not enough to achieve FVIII target levels during surgery or bleeding. We hypothesise that combined pharmacokinetic (PK)-guided administration of desmopressin and FVIII concentrate may improve dosing accuracy and reduces FVIII concentrate consumption.Methods and analysisIn the DAVID study, 50 patients with non-severe haemophilia A (FVIII:C ≥0.01 IU/mL) with a bleeding episode or undergoing surgery will receive desmopressin and FVIII concentrate combination treatment. The necessary dose of FVIII concentrate to reach FVIII target levels after desmopressin administration will be calculated with a population PK model. The primary endpoint is the proportion of patients reaching FVIII target levels during the first 72 hours after start of the combination treatment. This approach was successfully tested in one pilot patient who received perioperative combination treatment.Ethics and disseminationThe DAVID study was approved by the medical ethics committee of the Erasmus MC. Results of the study will be communicated trough publication in international scientific journals and presentation at (inter)national conferences.Trial registration numberNTR5383; Pre-results.