Papers by Veronique Stove
Pediatric Critical Care Medicine
OBJECTIVES In critically ill children, severely altered pharmacokinetics may result in subtherape... more OBJECTIVES In critically ill children, severely altered pharmacokinetics may result in subtherapeutic β-lactam antibiotic concentrations when standard pediatric dosing regimens are applied. However, it remains unclear how to recognize patients most at risk for suboptimal exposure and their outcome. This study aimed to: 1) describe target attainment for β-lactam antibiotics in critically ill children, 2) identify risk factors for suboptimal exposure, and 3) study the association between target nonattainment and clinical outcome. DESIGN Post hoc analysis of the "Antibiotic Dosing in Pediatric Intensive Care" study (NCT02456974, 2012-2019). Steady-state trough plasma concentrations were classified as therapeutic if greater than or equal to the minimum inhibitory concentration of the (suspected) pathogen. Factors associated with subtherapeutic concentrations and clinical outcome were identified by logistic regression analysis. SETTING The pediatric and cardiac surgery ICU of a Belgian tertiary-care hospital. PATIENTS One hundred fifty-seven patients (aged 1 mo to 15 yr) treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam, or meropenem. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Three hundred eighty-two trough concentrations were obtained from 157 patients (median age, 1.25 yr; interquartile range, 0.4-4.2 yr). Subtherapeutic concentrations were measured in 39 of 60 (65%), 43 of 48 (90%), and 35 of 49 (71%) of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam, and meropenem, respectively. Estimates of glomerular filtration rate (eGFR; 54% increase in odds for each sd increase in value, 95% CI, 0.287-0.736; p = 0.001) and the absence of vasopressor treatment (2.8-fold greater odds, 95% CI, 1.079-7.253; p = 0.034) were independently associated with target nonattainment. We failed to identify an association between antibiotic concentrations and clinical failure. CONCLUSIONS Subtherapeutic β-lactam concentrations are common in critically ill children and correlate with renal function. eGFR equations may be helpful in identifying patients who may require higher dosing. Future studies should focus on the impact of subtherapeutic concentrations on clinical outcome.
Annual Update in Intensive Care and Emergency Medicine 2013, 2013
Journal of Thoracic Oncology, 2009
Acta Clinica Belgica, 2015
Tijdschrift Voor Geneeskunde, 2016
Anti-K-antistoffen kunnen leiden tot ernstige hemolytische ziekte bij de foetus en de neonaat (HZ... more Anti-K-antistoffen kunnen leiden tot ernstige hemolytische ziekte bij de foetus en de neonaat (HZF/N). Het feit dat naast immuunafbraak van rode bloedcellen (RBC) ook onderdrukking van de foetale erytropoese een rol speelt in de pathogenese, maakt de diagnose, de aanpak en de opvolging bij anti-K-alloantistoffen enigszins afwijkend in vergelijking met andere onregelmatige antistoffen. Een 36-jarige zwangere vrouw werd verwezen naar een tertiair ziekenhuis wegens foetale cardiomegalie en ascites. Een analyse van het maternale bloed toonde de aanwezigheid van anti-K-antistoffen. Een uitgebreid echografisch onderzoek, waaronder een dopplermeting van de pieksystolische snelheid ter hoogte van de arteria cerebri media (MCA-PSV), wees op hydrops foetalis als gevolg van ernstige foetale anemie. De foetus kreeg vier intra-uteriene transfusies (IUT’s). Bij de geboorte was er geen anemie. Het postnatale verloop leek onverwikkeld. Een laboratoriumanalyse toonde aanvankelijk enkel uitgesproken ...
Therapeutic Drug Monitoring, 2011
Background: Meropenem and piperacillin are beta-lactam antibiotics that are widely used to treat ... more Background: Meropenem and piperacillin are beta-lactam antibiotics that are widely used to treat severe infections in the intensive care unit. Various chromatographic methods with UV detection have been were developed to measure total plasma concentrations of these antibiotics. The objective of this work was to develop a rapid method for the simultaneous detection of these drugs in human plasma. Materials and Methods: After blood collection in lithium heparin tubes, samples were quickly centrifuged and plasma was frozen at -20°C until analysis. Plasma samples were spiked with oxacillin as an internal standard and deproteinised using acetonitrile. The supernatant was analysed using ultraperformance-liquid chromatography tandem mass spectrometry (UPLCMS/MS). The compounds were chromatographically separated on a Waters Acquity UPLC system with a BEH C18 column (1.7 μm, 100 mm × 2.1 mm) kept at 50°C and a gradient elution of water and acetonitrile, both containing 0.1% formic acid. Comp...
Acta Clinica Belgica, 2013
Therapeutic Drug Monitoring, 2013
Therapeutic Drug Monitoring, 2021
Supplemental Digital Content is Available in the Text. Background: Therapeutic drug monitoring (T... more Supplemental Digital Content is Available in the Text. Background: Therapeutic drug monitoring (TDM) of busulfan is recommended for hematopoietic stem cell transplant recipients. Timely reporting of these TDM results is essential given the short administration period and the planned dose adjustments on day 2. The authors evaluated the performance of a new nanoparticle-based competitive immunoassay on two routine clinical chemistry analyzers and compared its performance to that of an in-house high-resolution mass spectrometry (HRMS) method. Methods: The MyCare Oncology Busulfan Assay Kit (Saladax Biomedical) was applied on two routine clinical chemistry analyzers (Abbott Architect c8000 and Roche Cobas c502) with a linearity range of 187–2000 ng/mL. The study evaluation measured imprecision and accuracy, sample probe carry-over, and dilution integrity. Method comparison with liquid chromatography (LC)-HRMS was performed using samples from patients undergoing busulfan treatment. Results: Within- and between-run coefficient of variations for both analyzers were ≤5.23% and ≤8.45%, respectively, across the busulfan concentration range. The obtained biases were ≤10.3%. Both analyzers met the acceptance criteria for sample probe carry-over and dilution integrity. Agreement between the immunoassay and LC-HRMS was high: 92% and 89% of the samples measured on Architect and Cobas, respectively, were within the ±15% limit compared to the corresponding LC-HRMS results. Conclusions: Overall, good analytical performance and high agreement with LC-HRMS results were obtained for the immunoassay installed on both routine clinical chemistry analyzers. Therefore, this assay could be implemented as a valid alternative for LC methods in clinical laboratories on different open-channel clinical chemistry analyzers, resulting in shorter turn-around times for reporting busulfan TDM results with subsequent faster dosage adjustments.
International Journal of Laboratory Hematology, 2020
Dear Editors, Clinical laboratories are responsible for the reference intervals reported on their... more Dear Editors, Clinical laboratories are responsible for the reference intervals reported on their laboratory reports, as specified by the International Organization for Standardization standard 15 189. Although required by the directive on in vitro diagnostic medical devices in the European Union (98/79/EC), manufacturers' information about the
Journal of Critical Care, 2019
Clinical Chemistry and Laboratory Medicine (CCLM), 2019
In 2016, Vogel et al. reported about the non-linearity within the primary measurement range of li... more In 2016, Vogel et al. reported about the non-linearity within the primary measurement range of lipase assays, in which a discontinuity of results between 300 and 400 U/L was described [1]. The remarkable data were ascribed to a non-linearity of the Roche colorimetric lipase assay. To overcome this non-linearity, Roche Diagnostics changed their lipase application. In a first attempt, they changed the dilution from 1:10 to 1:2 for lipase activities >300 U/L. More recently, sample volume and assay points were adapted, together with a backswitch to a 1:10 dilution in decreased mode, because of improved linearity in the higher measuring range (see Table 1) [2]. In line with the paper by Vogel et al., we investigated the cumulative frequency of all lipase results in our lab information system (inpatients and outpatients), filtered on the result range of interest for this study (200–900 U/L for Roche assays). Results obtained with the most recent Roche Cobas 8000 c502 lipase application (in the period 01/05/2018–25/01/2019) are presented in Figure 1E.
Journal of Critical Care, 2019
Increased renal elimination is the leading cause for subtherapeutic concentrations of renally cle... more Increased renal elimination is the leading cause for subtherapeutic concentrations of renally cleared antibiotics and it has been hypothesized that brain damaged patients in the intensive care unit (ICU) are particularly at risk. The objective of this study is to determine the prevalence of subtherapeutic piperacillin concentrations in neurocritical patients and to investigate if having a neurocritical diagnosis is a risk factor for this. Materials and Methods: Single center retrospective analysis of a prospective cohort study of adult ICU patients receiving continuous infusion piperacillin/tazobactam. Patients were categorized as either having a neurocritical diagnosis or not. An unbound piperacillin concentration >4x the epidemiologic cutoff value (ECOFF) of Pseudomonas aeruginosa was selected as the PKPD target of choice. Multivariable logistic regression was performed to identify risk factors for subtherapeutic piperacillin concentrations. Results: 356 patients had a measured creatinine clearance (mCrCl) and matched piperacillin concentration, 52 of which had a neurocritical diagnosis. Subtherapeutic piperacillin concentrations
International Journal of Antimicrobial Agents, 2019
Journal of Critical Care, 2019
Purpose Standard dosing and intermittent bolus application (IB) are important risk factors for ph... more Purpose Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. Methods This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2-4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. Results PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CL PIP): no RRT CL PIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CL PIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CL PIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m 2 significantly increased CL PIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p < 0.0005), whereas high CrCL led to non-target attainment (p < 0.0005). Patients with target attainment (33-64 mg/L) within the first 24 h exhibited the lowest hospital mortality rates (13.9% [n = 23/166], p < 0.005). Those with target non-attainment demonstrated higher mortality rates (≤ 32 mg/L; 20.8% [n = 10/49] ≥ 64 mg/L; 29.4% [n = 79/269]). Conclusion TDM-guided CI of PIP is safe in critically ill patients and improves PK-target attainment. Exposure to defined PK-targets impacts patient mortality while lower and higher than intended SCs may influence the outcome of critically ill patients. Renal function and renal replacement therapy are main determinants of PK-target attainment. These results are only valid for CI of PIP and not for prolonged or intermittent bolus administration of PIP.
Clinical chemistry and laboratory medicine, Jan 27, 2018
Recently, urine test strip readers have become available for automated test strip analysis. We ex... more Recently, urine test strip readers have become available for automated test strip analysis. We explored the possibilities of the Sysmex UC-3500 automated urine chemistry analyzer based on complementary metal oxide semiconductor (CMOS) sensor technology with regard to accuracy of leukocyte esterase and hemoglobin peroxidase results. We studied the influence of possible confounders on these measurements. Reflectance data of leukocyte esterase and hemoglobin peroxidase were measured using CMOS technology on the Sysmex UC-3500 automated urine chemistry analyzer. Analytical performance (imprecision, LOQ) as well as the correlation with white blood cell (WBC) and red blood cell (RBC) counts (Sysmex UF-5000) were studied. Furthermore, the influence of urinary dilution, haptoglobin, pH and ascorbic acid as confounders was determined. Within- and between-run imprecision (reflectance signal) ranged from 1.1% to 3.6% and 0.9% to 4.2% for peroxidase and 0.4% to 2.5% and 0.4% to 3.3% for leukocy...
Journal of Antimicrobial Chemotherapy, 2018
Background: Several population pharmacokinetic (PopPK) models for meropenem dosing in ICU patient... more Background: Several population pharmacokinetic (PopPK) models for meropenem dosing in ICU patients are available. It is not known to what extent these models can predict meropenem concentrations in an independent validation dataset when meropenem is infused continuously. Patients and methods: A PopPK model was developed with concentration-time data collected from routine care of 21 ICU patients (38 samples) receiving continuous infusion meropenem. The predictability of this model and seven other published PopPK models was studied using an independent dataset that consisted of 47 ICU patients (161 samples) receiving continuous infusion meropenem. A statistical comparison of imprecision (mean square prediction error) and bias (mean prediction error) was conducted. Results: A one-compartment model with linear elimination and creatinine clearance as a covariate of clearance best described our data. The mean + SD parameter estimate for CL was 9.89+3.71 L/h. The estimated volume of distribution was 48.1 L. The different PopPK models showed a bias in predicting serum concentrations from the validation dataset that ranged from #8.76 to 7.06 mg/L. Imprecision ranged from 9.90 to 42.1 mg/L. Conclusions: Published PopPK models for meropenem vary considerably in their predictive performance when validated in an external dataset of ICU patients receiving continuous infusion meropenem. It is necessary to validate PopPK models in a target population before implementing them in a therapeutic drug monitoring program aimed at optimizing meropenem dosing.
Clinical Biochemistry, 2018
Background: Point-of-care blood gas test results may benefit therapeutic decision making by their... more Background: Point-of-care blood gas test results may benefit therapeutic decision making by their immediate impact on patient care. We evaluated the (pre-)analytical performance of a novel cartridge-type blood gas analyzer, the GEM Premier 5000 (Werfen), for the determination of pH, partial carbon dioxide pressure (pCO 2), partial oxygen pressure (pO 2), sodium (Na +), potassium (K +), chloride (Cl −), ionized calcium (i Ca 2 +), glucose, lactate, and total hemoglobin (tHb). Methods: Total imprecision was estimated according to the CLSI EP5-A2 protocol. The estimated total error was calculated based on the mean of the range claimed by the manufacturer. Based on the CLSI EP9-A2 evaluation protocol, a method comparison with the Siemens RapidPoint 500 and Abbott i-STAT CG8 + was performed. Obtained data were compared against preset quality specifications. Interference of potential pre-analytical confounders on co-oximetry and electrolyte concentrations were studied. Results: The analytical performance was acceptable for all parameters tested. Method comparison demonstrated good agreement to the RapidPoint 500 and i-STAT CG8 +, except for some parameters (RapidPoint 500: pCO 2 , K + , lactate and tHb; i-STAT CG8 +: pO 2 , Na + , i Ca 2 + and tHb) for which significant differences between analyzers were recorded. No interference of lipemia or methylene blue on CO-oximetry results was found. On the contrary, significant interference for benzalkonium and hemolysis on electrolyte measurements were found, for which the user is notified by an interferent specific flag. Conclusion: Identification of sample errors from pre-analytical sources, such as interferences and automatic corrective actions, along with the analytical performance, ease of use and low maintenance time of the instrument, makes the evaluated instrument a suitable blood gas analyzer for both POCT and laboratory use.
Uploads
Papers by Veronique Stove