scholarly journals P42 External validation of model-based dosing guidelines for vancomycin, gentamicin and tobramycin in critically ill children

2019 ◽  
Vol 104 (6) ◽  
pp. e34.2-e34
Author(s):  
S Hartman ◽  
S Zwaag ◽  
L Orriëns ◽  
T Poel ◽  
M de Hoop - Sommen ◽  
...  
Keyword(s):  
Critically Ill ◽  
Clinical Laboratory ◽  
External Validation ◽  
Interindividual Variation ◽  
Critically Ill Children ◽  
Target Range ◽  
Future Research ◽  
Target Attainment ◽  
Model Based ◽  
Trough Concentrations

BackgroundPharmacokinetic models are frequently used to simulate dosing strategies for special populations, including critically ill children. The Dutch Pediatric Formulary (DPF) partially bases its guidelines on these models. However, prospective validation of updated dosing regimens is rare. We aimed to identify target attainment and safety of vancomycin, gentamicin and tobramycin after a dose update in the DPF for critically ill neonates and children.MethodsRetropsective cohort study in PICU and NICU patients receiving vancomycin, gentamicin or tobramycin between January 2015 and March 2017 in 2 university hospitals. Demographic clinical laboratory and TDM-data were collected. Target (steady state) trough concentrations for vancomycin, gentamicin and tobramycin used were 10–15, ≤1 and ≤1 mg/l, respectively. Target gentamicin peak concentrations used were 8–12 mg/l.Results486 patients were included in total (165 vancomycin, 97 gentamicin and 224 tobramycin). Trough concentrations of vancomycin, gentamicin and tobramycin were within the target range in 37.5%, 85.3% and 77.2% of patients, respectively. Target attainment of gentamicin peak concentrations in NICU patients was 31%. Non-target trough concentrations were most prevalent in term NICU patients (vancomycin 70%, gentamicin 26% and tobramycin 36.8%). Gentamicin peak concentrations were subtherapeutic in 91% and 45.5% for term and preterm NICU patients, respectively. Creatinine concentrations correlated positively with antibiotic concentrations (correlation coefficient range 0.46–0.54, p≤0.01 in all cohorts).ConclusionDespite recent model-based dosing alterations, sub- and supratherapeutic concentrations of vancomycin, gentamicin and tobramycin are still frequent in critically ill children. Linear dose alterations did offer improvements in target attainment, but did not fully address all relevant covariates that contribute to the large interindividual variation in clearance and/or volume of distribution in these patients. Creatinine clearance was consistently correlated with concentrations of all 3 drugs, but future research is needed to identify whether including this parameter in dosing can improve target attainment and safety.Disclosure(s)Nothing to disclose

scholarly journals Pharmacodynamic Target Attainment for Meropenem and Piperacillin/Tazobactam Using a PK/PD-based Dosing Calculator in Critically Ill Patients

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S27-S27 ◽  
Author(s):  
Emily Heil ◽  
David P Nicolau ◽  
Gwen Robinson ◽  
Andras Farkas ◽  
Kerri Thom
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Future Research ◽  
Target Attainment ◽  
Research Support ◽  
Dosing Strategies ◽  
Trough Concentrations ◽  
Culture Positive ◽  
Antibiotic Dosing

Abstract Background Unbound plasma concentrations of β-lactam antibiotics vary widely and attainment of PK/PD targets is highly variable in critically ill patients, which may affect microbiologic cure or contribute to toxicity. PK/PD-based antibiotic dosing programs may provide more accurate doses that achieve predicted targets for a cultured organism. Methods This was a single center, prospective study of critically ill patients with culture positive gram-negative infections treated with meropenem (MEM) or piperacillin/tazobactam (TZP). A PK/PD-based antibiotic dosing app was used to select doses that had a probability of target attainment (PTA) of 90% or greater for time above MIC (fT>MIC) of at least 40% for MEM and 50% for TZP. Total meropenem, piperacillin and tazobactam mid-point and trough concentrations were obtained at steady-state and adjusted for protein binding, to assess target attainment. Results Thirty-six patients were enrolled; 20 received MEM and 16 TZP. Antibiotic concentrations varied widely amongst patients, particularly with TZP. MEM and TZP concentrations are displayed in Table 1 and Figure 1. Doses evaluated for >90% probability of target attainment in the dosing calculator differed from standard package labeled doses for 25% (5/20) of MEM and 18.8% (3/16) of TZP patients. All (20/20) MEM and 94% (15/16) TZP patients maintained fT>MIC for the entire dosing interval. Conclusion A PK/PD based antibiotic dosing calculator that provides individualized β-lactam doses can lead to altered doses that may increase probability of target attainment in critically ill patients. Future research is needed to review the relevance of PK/PD-based dose adjustments on clinical outcomes. Disclosures D. P. Nicolau, Shionogi & Co.: Research Contractor, Research support; A. Farkas, Optimum Dosing Strategies: Employee, Salary.

scholarly journals Effectiveness and Safety of Potassium Replacement in Critically Ill Patients: A Retrospective Cohort Study

2019 ◽  
Vol 39 (1) ◽  
pp. e13-e18
Author(s):  
Drayton A. Hammond ◽  
Jarrod King ◽  
Niranjan Kathe ◽  
Kristina Erbach ◽  
Jelena Stojakovic ◽  
...  
Keyword(s):  
Intensive Care ◽  
Critically Ill ◽  
Serum Potassium ◽  
Critically Ill Patients ◽  
Odds Ratio ◽  
Target Range ◽  
Target Attainment ◽  
Serum Potassium Concentration ◽  
Rule Of Thumb ◽  
Potassium Replacement

Background Rules of thumb for potassium replacement are used in intensive care units despite minimal empirical validation. Objective To evaluate the effectiveness and safety of rule-of-thumb potassium replacement in critically ill patients with mild and moderate hypokalemia. Methods A retrospective, observational study was done of patients with mild (potassium, 3-3.9 mEq/L) and moderate (potassium, 2-2.9 mEq/L) hypokalemia admitted to a medical intensive care unit who received potassium replacement. Expected and actual frequencies of replacement that achieved target potassium concentrations (≥ 4 mEq/L) were compared by using a χ2 test. Logistic regression analysis was used to assess whether rule-of-thumb administration affected the probability of target attainment within 24 hours of replacement. Results Serum potassium concentrations were checked within 24 hours after potassium replacement on 354 of 577 days (61.4%) when replacement was provided. Concentrations were within target range in 82 instances (23.2%). Of 62 episodes of replacement expected to achieve the target according to the rule-of-thumb estimation, 22 did (35%). Rule-of-thumb administration was associated with greater likelihood of target attainment (odds ratio, 2.12; 95% CI, 1.18-3.85; P = .01). This difference in likelihood remained significant after adjustment for covariates (odds ratio, 2.18; 95% CI, 1.04-4.56; P = .04). Conclusion In critically ill patients given potassium replacement without regard to a formal protocol, the target serum potassium concentration was achieved more often than expected according to the rule-of-thumb estimation but less than one-third of the time.

scholarly journals P43 Pharmacokinetics and target attainment of antibiotics in critically ill children – a systematic review of current literature

2019 ◽  
Vol 104 (6) ◽  
pp. e35.1-e35
Author(s):  
S Hartman ◽  
R Brüggemann ◽  
L Orriëns ◽  
N Dia ◽  
M Schreuder ◽  
...  
Keyword(s):  
Critically Ill ◽  
Patient Population ◽  
Current Knowledge ◽  
Volume Of Distribution ◽  
Critically Ill Children ◽  
Therapeutic Drug ◽  
Healthy Children ◽  
Target Attainment ◽  
Critically Ill Adults ◽  
Ill Adults

BackgroundPharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). To what extent this affects the PK of antibiotics in critically children is largely unknown. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.MethodsSystematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, trough concentrations, AUC, probability of target attainment, and elimination half-life.Results45 relevant articles were identified. Studies focusing on vancomycin were most prevalent (15/45). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a larger Vd and higher Cl than healthy children and critically ill adults. Reduced target attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 32/45 articles included information on both Vd and Cl, but a dosing advice was given in only 18 articles.ConclusionThe majority of studies focus on agents where therapeutic drug monitoring is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl that is observed in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.Disclosure(s)Nothing to disclose

scholarly journals External Validation of Model-Based Dosing Guidelines for Vancomycin, Gentamicin, and Tobramycin in Critically Ill Neonates and Children: A Pragmatic Two-Center Study

2020 ◽  
Vol 22 (4) ◽  
pp. 433-444 ◽  
Author(s):  
Stan J. F. Hartman ◽  
Lynn B. Orriëns ◽  
Samanta M. Zwaag ◽  
Tim Poel ◽  
Marika de Hoop ◽  
...  
Keyword(s):  
Critically Ill ◽  
External Validation ◽  
Model Based ◽  
Critically Ill Neonates ◽  
Center Study

scholarly journals Pediatric Fibrinogen PART II—Overview of Indications for Fibrinogen Use in Critically Ill Children

2021 ◽  
Vol 9 ◽  
Author(s):  
Gemma Louise Crighton ◽  
Elise J. Huisman
Keyword(s):  
Critically Ill ◽  
Current Knowledge ◽  
Coagulation Factor ◽  
Critically Ill Children ◽  
Future Research ◽  
Considerable Variability ◽  
Disseminated Intravascular Coagulopathy ◽  
Clinical Indications ◽  
Replacement Product ◽  
Intravascular Coagulopathy

Bleeding is frequently seen in critically ill children and is associated with increased morbidity and mortality. Fibrinogen is an essential coagulation factor for hemostasis and hypofibrinogenemia is an important risk factor for bleeding in pediatric and adult settings. Cryoprecipitate and fibrinogen concentrate are often given to critically ill children to prevent bleeding and improve fibrinogen levels, especially in the setting of surgery, trauma, leukemia, disseminated intravascular coagulopathy, and liver failure. The theoretical benefit of fibrinogen supplementation to treat hypofibrinogenemia appears obvious, yet the evidence to support fibrinogen supplementation in children is sparce and clinical indications are poorly defined. In addition, it is unknown what the optimal fibrinogen replacement product is in children and neonates or what the targets of treatment should be. As a result, there is considerable variability in practice. In this article we will review the current pediatric and applicable adult literature with regard to the use of fibrinogen replacement in different pediatric critical care contexts. We will discuss the clinical indications for fibrinogen supplementation in critically ill children and the evidence to support their use. We summarize by highlighting current knowledge gaps and areas for future research.

scholarly journals Impact of vancomycin protein binding on target attainment in critically ill children: back to the drawing board?

2016 ◽  
pp. dkw495 ◽  
Author(s):  
Pieter A. J. G. De Cock ◽  
Sarah Desmet ◽  
Annick De Jaeger ◽  
Dominique Biarent ◽  
Evelyn Dhont ◽  
...  
Keyword(s):  
Protein Binding ◽  
Critically Ill ◽  
Critically Ill Children ◽  
Target Attainment ◽  
Drawing Board

scholarly journals Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients

2021 ◽  
Vol 9 (10) ◽  
pp. 2068
Author(s):  
Ruth Van Daele ◽  
Joost Wauters ◽  
Katrien Lagrou ◽  
Raphaël Denooz ◽  
Marie-Pierre Hayette ◽  
...  
Keyword(s):  
Critically Ill ◽  
Trough Concentration ◽  
Critically Ill Patients ◽  
Inhibitory Concentration ◽  
Antifungal Drugs ◽  
Target Attainment ◽  
Augmented Renal Clearance ◽  
Time Curve ◽  
Concentration Time ◽  
Trough Concentrations

Background: Fluconazole is one of the oldest antifungal drugs. Previous studies have raised concerns considering variability in exposure and inadequate target attainment in critically ill patients. The current study aims to define variability and target attainment for fluconazole exposure in a large group of critically ill patients. Methods: In this pharmacokinetic study, daily plasma trough samples and, if possible, 24 h urine samples were collected to determine fluconazole concentration. A minimum target trough concentration of 10–15 mg/L was selected, corresponding to a free area under the concentration–time curve above the minimum inhibitory concentration (fAUC/MIC) of at least 100 for an MIC of 4 mg/L. Covariates that significantly influenced fluconazole exposure were identified. Results: In total, 288 plasma samples from 43 patients, with a median age of 66 years, were included. The median fluconazole trough concentration was 22.9 mg/L. A notable component of the measured concentrations was below the target trough concentrations (13% <10 mg/L and 27% <15 mg/L). The intra- and intersubject variability were 28.3% and 50.5%, respectively. The main covariates determining fluconazole exposure were the administered dose (mg/kg), augmented renal clearance, and renal replacement therapy. Conclusions: Fluconazole trough concentrations are variable in critically ill patients and a considerable number of these concentrations was below the predefined target trough concentrations.

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