First‐Dose Vancomycin Pharmacokinetics Versus Empiric Dosing on Area‐Under‐the‐Curve Target Attainment in Critically Ill Patients

2020 ◽  
Vol 40 (12) ◽  
pp. 1210-1218
Author(s):  
Alexander H. Flannery ◽  
Natalie L. Delozier ◽  
Samuel A. Effoe ◽  
Katie L. Wallace ◽  
Aaron M. Cook ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Area Under The Curve ◽  
Target Attainment

scholarly journals Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured Versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 557
Author(s):  
Matthias Gijsen ◽  
Erwin Dreesen ◽  
Ruth Van Daele ◽  
Pieter Annaert ◽  
Yves Debaveye ◽  
...  
Keyword(s):  
Renal Function ◽  
Cohort Study ◽  
Protein Binding ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Observational Cohort Study ◽  
Target Attainment ◽  
Binding Model ◽  
Observational Cohort ◽  
The Impact

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.

scholarly journals Usefulness of sialic acid for diagnosis of sepsis in critically ill patients: a retrospective study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bo Yao ◽  
Wen-juan Liu ◽  
Di Liu ◽  
Jin-yan Xing ◽  
Li-juan Zhang
Keyword(s):  
Sialic Acid ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Incomplete Data ◽  
Acid Level ◽  
Operating Characteristic ◽  
Area Under The Curve ◽  
Diagnostic Efficacy ◽  
Receiver Operating Characteristic Curves ◽  
Sensitivity Specificity

Abstract Background Early diagnosis of sepsis is very important. It is necessary to find effective and adequate biomarkers in order to diagnose sepsis. In this study, we compared the value of sialic acid and procalcitonin for diagnosing sepsis. Methods Newly admitted intensive care unit patients were enrolled from January 2019 to June 2019. We retrospectively collected patient data, including presence of sepsis or not, procalcitonin level and sialic acid level. Receiver operating characteristic curves for the ability of sialic acid, procalcitonin and combination of sialic acid and procalcitonin to diagnose sepsis were carried out. Results A total of 644 patients were admitted to our department from January 2019 to June 2019. The incomplete data were found in 147 patients. Finally, 497 patients data were analyzed. The sensitivity, specificity and area under the curve for the diagnosis of sepsis with sialic acid, procalcitonin and combination of sialic acid and procalcitonin were 64.2, 78.3%, 0.763; 67.9, 84.0%, 0.816 and 75.2, 84.6%, 0.854. Moreover, sialic acid had good values for diagnosing septic patients with viral infection, with 87.5% sensitivity, 82.2% specificity, and 0.882 the area under the curve. Conclusions Compared to procalcitonin, sialic acid had a lower diagnostic efficacy for diagnosing sepsis in critically ill patients. However, the combination of sialic acid and procalcitonin had a higher diagnostic efficacy for sepsis. Moreover, sialic acid had good value for diagnosing virus-induced sepsis.

scholarly journals Population Pharmacokinetics and Probability of Target Attainment of Different Dosing Regimens of Ceftazidime in Critically Ill Patients with a Proven or Suspected Pseudomonas aeruginosa Infection

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 612
Author(s):  
Annabel Werumeus Buning ◽  
Caspar J. Hodiamont ◽  
Natalia M. Lechner ◽  
Margriet Schokkin ◽  
Paul W. G. Elbers ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Hematologic Malignancy ◽  
Compartment Model ◽  
Target Attainment ◽  
Worst Case ◽  
Optimal Dosing ◽  
Population Pk ◽  
Pseudomonas Aeruginosa Infection

Altered pharmacokinetics (PK) of hydrophilic antibiotics in critically ill patients is common, with possible consequences for efficacy and resistance. We aimed to describe ceftazidime population PK in critically ill patients with a proven or suspected Pseudomonas aeruginosa infection and to establish optimal dosing. Blood samples were collected for ceftazidime concentration measurement. A population PK model was constructed, and probability of target attainment (PTA) was assessed for targets 100% T > MIC and 100% T > 4 × MIC in the first 24 h. Ninety-six patients yielded 368 ceftazidime concentrations. In a one-compartment model, variability in ceftazidime clearance (CL) showed association with CVVH. For patients not receiving CVVH, variability in ceftazidime CL was 103.4% and showed positive associations with creatinine clearance and with the comorbidities hematologic malignancy, trauma or head injury, explaining 65.2% of variability. For patients treated for at least 24 h and assuming a worst-case MIC of 8 mg/L, PTA was 77% for 100% T > MIC and 14% for 100% T > 4 × MIC. Patients receiving loading doses before continuous infusion demonstrated higher PTA than patients who did not (100% T > MIC: 95% (n = 65) vs. 13% (n = 15); p < 0.001 and 100% T > 4 × MIC: 20% vs. 0%; p = 0.058). The considerable IIV in ceftazidime PK in ICU patients could largely be explained by renal function, CVVH use and several comorbidities. Critically ill patients are at risk for underexposure to ceftazidime when empirically aiming for the breakpoint MIC for P. aeruginosa. A loading dose is recommended.

Performance of Automated Telemetry in Diagnosing QT Prolongation in Critically Ill Patients

2021 ◽  
Vol 30 (6) ◽  
pp. 466-470
Author(s):  
Enrique Calvo-Ayala ◽  
Vince Procopio ◽  
Hayk Papukhyan ◽  
Girish B. Nair
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Demographic Data ◽  
Area Under The Curve ◽  
Qt Prolongation ◽  
Altman Analysis ◽  
Poor Agreement ◽  
Bland Altman Analysis ◽  
Prolonged Qt ◽  
Definition Of

Background QT prolongation increases the risk of ventricular arrhythmia and is common among critically ill patients. The gold standard for QT measurement is electrocardiography. Automated measurement of corrected QT (QTc) by cardiac telemetry has been developed, but this method has not been compared with electrocardiography in critically ill patients. Objective To compare the diagnostic performance of QTc values obtained with cardiac telemetry versus electrocardiography. Methods This prospective observational study included patients admitted to intensive care who had an electrocardiogram ordered simultaneously with cardiac telemetry. Demographic data and QTc determined by electrocardiography and telemetry were recorded. Bland-Altman analysis was done, and correlation coefficient and receiver operating characteristic (ROC) coefficient were calculated. Results Fifty-one data points were obtained from 43 patients (65% men). Bland-Altman analysis revealed poor agreement between telemetry and electrocardiography and evidence of fixed and proportional bias. Area under the ROC curve for QTc determined by telemetry was 0.9 (P &lt; .001) for a definition of prolonged QT as QTc ≥ 450 milliseconds in electrocardiography (sensitivity, 88.89%; specificity, 83.33%; cutoff of 464 milliseconds used). Correlation between the 2 methods was only moderate (r = 0.6, P &lt; .001). Conclusions QTc determination by telemetry has poor agreement and moderate correlation with electrocardiography. However, telemetry has an acceptable area under the curve in ROC analysis with tolerable sensitivity and specificity depending on the cutoff used to define prolonged QT. Cardiac telemetry should be used with caution in critically ill patients.

scholarly journals Galectin-3 in Critically Ill Patients with Sepsis and/or Trauma: A Good Predictor of Outcome or Not?

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Jasna Jevdjic ◽  
Maja Surbatovic ◽  
Snezana Milosavljevic ◽  
Goran Rondovic ◽  
Ivan Stanojevic ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Good Predictor ◽  
Injury Severity ◽  
Area Under The Curve ◽  
University Hospital ◽  
Youden Index ◽  
Lethal Outcome ◽  
Galectin 3

Abstract Severe sepsis and/or trauma complicated with multiple organ dysfunction syndrome are leading causes of death in critically ill patients. The aim of this prospective, observational, single centre study was to assess the prognostic value of galectin-3 regarding outcome in critically ill patients with severe trauma and/or severe sepsis. The outcome measure was hospital mortality. In total, 75 critically ill patients who were admitted to the intensive care unit of the tertiary university hospital were enrolled in a prospective observational study. Blood samples were collected upon fulfilling Sepsis-3 criteria and for a traumatized Injury Severity Score > 25 points. Levels of galectin-3 were significantly higher in nonsurvivors on the day of enrolment - Day 1 (p<0.05). On Day 1, the area under the curve (AUC) for the galectin-3 for lethal outcome was 0.602. At a cut-off level of 262.82 ng/mL, the sensitivity was 53%, and the specificity was 69.7%, which was objectively determined by a Youden index of 0.20. The discriminative power of galectin-3 in predicting outcome was statistically significant. Galectin-3 on Day 1 is a fairly good predictor of lethal outcome.

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 Population Pharmacokinetics of Piperacillin following Continuous Infusion in Critically Ill Patients and Impact of Renal Function on Target Attainment

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Vibeke Klastrup ◽  
Anders Thorsted ◽  
Merete Storgaard ◽  
Steffen Christensen ◽  
Lena E. Friberg ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Bacterial Infections ◽  
Population Pharmacokinetic ◽  
Target Attainment ◽  
Content Type ◽  
Daily Dose ◽  
Linear Elimination ◽  
Severe Infections

ABSTRACT Pharmacokinetic changes are often seen in patients with severe infections. Administration by continuous infusion has been suggested to optimize antibiotic exposure and pharmacokinetic/pharmacodynamic (PK/PD) target attainment for β-lactams. In an observational study, unbound piperacillin concentrations (n = 196) were assessed in 78 critically ill patients following continuous infusion of piperacillin-tazobactam (ratio 8:1). The initial dose of 8, 12, or 16 g (piperacillin component) was determined by individual creatinine clearance (CRCL). Piperacillin concentrations were compared to the EUCAST clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter), and the following PK/PD targets were evaluated: 100% free time (fT) > 1× MIC and 100% fT > 4× MIC. A population pharmacokinetic model was developed using NONMEM 7.4.3 consisting of a one-compartment disposition model with linear elimination separated into nonrenal and renal (linearly increasing with patient CRCL) clearances. Target attainment was predicted and visualized for all individuals based on the utilized CRCL dosing algorithm. The target of 100% fT > 1× MIC was achieved for all patients based on the administered dose, but few patients achieved the target of 100% fT > 4× MIC. Probability of target attainment for a simulated cohort of patients showed that increasing the daily dose by 4-g increments (piperacillin component) did not result in substantially improved target attainment for the 100% fT > 4× MIC target. To conclude, in patients with high CRCL combined with high-MIC bacterial infections, even a continuous infusion (CI) regimen with a daily dose of 24 g may be insufficient to achieve therapeutic concentrations.

scholarly journals Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

2020 ◽  
Vol 76 (7) ◽  
pp. 957-967
Author(s):  
Alan Abdulla ◽  
Omar Rogouti ◽  
Nicole G. M. Hunfeld ◽  
Henrik Endeman ◽  
Annemieke Dijkstra ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Target Attainment

Early target attainment of continuous infusion piperacillin/tazobactam and meropenem in critically ill patients: A prospective observational study

2019 ◽  
Vol 52 ◽  
pp. 75-79 ◽  
Author(s):  
Sofie A.M. Dhaese ◽  
Alexander D.J. Thooft ◽  
Andras Farkas ◽  
Jeffrey Lipman ◽  
Alain G. Verstraete ◽  
...  
Keyword(s):  
Observational Study ◽  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Prospective Observational Study ◽  
Target Attainment
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