scholarly journals New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients

2016 ◽  
Vol 60 (8) ◽  
pp. 4750-4756 ◽  
Author(s):  
Stefano Cristallini ◽  
Maya Hites ◽  
Hakim Kabtouri ◽  
Jason A. Roberts ◽  
Marjorie Beumier ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Loading Dose ◽  
Dosing Regimen ◽  
Median Dose ◽  
New Agents ◽  
Gram Positive Bacteria ◽  
Gault Formula ◽  
Mixed Intensive Care Unit ◽  
Dosing Strategy

ABSTRACTDespite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment.

Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen

2005 ◽  
Vol 43 (08) ◽  
pp. 360-369 ◽  
Author(s):  
B. Georges ◽  
J.-M. Conil ◽  
P. Cougot ◽  
J.-F. Decun ◽  
M. Archambaud ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Dosing Regimen

scholarly journals Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Uwe Liebchen ◽  
Hanna Salletmeier ◽  
Simon Kallee ◽  
Christina Scharf ◽  
Lucas Huebner ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Extreme Values ◽  
Stochastic Simulations ◽  
Loading Dose ◽  
Case Scenario ◽  
Worst Case ◽  
Worst Case Scenario ◽  
Optimal Loading

AbstractThe aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients. A previously published and successfully evaluated pharmacokinetic model of critically ill patients was used for stochastic simulations of virtual patients. Maintenance doses administered as continuous infusion of 1.5–6 g/24 h with preceding loading doses (administered as 30 min infusion) of 0.15–2 g were investigated. In addition to the examination of the influence of individual covariates, a best-case and worst-case scenario were simulated. Dosing regimens were considered adequate if the 5th percentile of the concentration–time profile did not drop at any time below four times the S/I breakpoint (= 2 mg/L) of Pseudomonas aeruginosa according to the EUCAST definition. Low albumin concentrations, high body weight and high creatinine clearances increased the required loading dose. A maximum loading dose of 0.33 g resulted in sufficient plasma concentrations when only one covariate showed extreme values. If all three covariates showed extreme values (= worst-case scenario), a loading dose of 0.5 g was necessary. Higher loading doses did not lead to further improvements of target attainment. We recommend the administration of a loading dose of 0.5 g meropenem over 30 min immediately followed by continuous infusion.

836: Weight- Versus Non-Weight-Based Continuous-Infusion Fentanyl Dosing Regimen in Critically Ill Adults

2020 ◽  
Vol 49 (1) ◽  
pp. 415-415
Author(s):  
Sahar Matloub ◽  
Rachel Tendler ◽  
William Bender ◽  
Kelly Ouellette
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Dosing Regimen ◽  
Critically Ill Adults ◽  
Ill Adults

Population pharmacokinetics of ceftriaxone administered as continuous or intermittent infusion in critically ill patients

2020 ◽  
Vol 75 (6) ◽  
pp. 1554-1558 ◽  
Author(s):  
E Leegwater ◽  
B V C Kraaijenbrink ◽  
D J A R Moes ◽  
I M Purmer ◽  
E B Wilms
Keyword(s):  
Serum Albumin ◽  
Protein Binding ◽  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Intermittent Infusion ◽  
Albumin Concentration ◽  
Serum Albumin Concentration ◽  
Dosing Regimen ◽  
G 12

Abstract Objectives To describe the population pharmacokinetics and protein-binding characteristics of unbound ceftriaxone administered as continuous or intermittent infusion. Additionally, to determine the optimal dosing regimen in critically ill patients. Methods A pharmacokinetic study was performed in the ICU of a tertiary teaching hospital. Patients were treated with ceftriaxone as continuous or intermittent infusion. A population pharmacokinetic model was developed with non-linear mixed-effects analysis. Subsequently, the PTA of a 100% T>MIC was assessed for influential patient characteristics using Monte Carlo simulation. Results Fifty-five patients were included. The pharmacokinetics of ceftriaxone was best described by a one-compartment model with non-linear saturable protein binding including the following covariates: body weight, estimated CLCR, serum albumin concentration and mode of administration. For pathogens with an MIC of 1 mg/L, the simulation demonstrated that intermittent infusion of 2 g/24 h only resulted in a ≥90% PTA in patients with a reduced CLCR (0–60 mL/min). Intermittent infusion of 2 g/12 h led to sufficient exposure if CLCR was 0–90 mL/min and continuous infusion of 2 g/24 h led to a ≥90% PTA in all simulations (CLCR 0–180 mL/min). Conclusions In the critically ill, the clearance of unbound ceftriaxone is closely related to CLCR. Furthermore, ceftriaxone protein binding is saturable, variable and dependent on serum albumin concentration. Intermittent dosing of 2 g/24 h ceftriaxone leads to subtherapeutic exposure in patients with a normal or increased CLCR. Treating these patients with continuous infusion of 2 g/24 h is more effective than an intermittent dosing regimen of 2 g/12 h.

scholarly journals High-Dose Continuous Oxacillin Infusion Results in Achievement of Pharmacokinetics Targets in Critically Ill Patients with Deep Sternal Wound Infections following Cardiac Surgery

2014 ◽  
Vol 58 (9) ◽  
pp. 5448-5455 ◽  
Author(s):  
Nicolas Nesseler ◽  
Marie-Clémence Verdier ◽  
Yoann Launey ◽  
Alexandre Malherbe ◽  
Marine Dermu ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
High Dose ◽  
Loading Dose ◽  
Wound Infections ◽  
Sternal Wound Infections ◽  
Deep Sternal Wound Infections

ABSTRACTKnowledge regarding antimicrobial therapy strategies in deep sternal wound infections (DSWI) following cardiac surgery is limited. Therefore, we aimed to determine the steady-state plasma and mediastinal concentrations of oxacillin administered by continuous infusion in critically ill patients with DSWI and to compare these concentrations with the susceptibility of staphylococci recovered. A continuous infusion of oxacillin (150 to 200 mg/kg of body weight/24 h) was administered after a loading dose (50 mg/kg). Plasma and mediastinal concentrations of total and unbound oxacillin were determined 4 h after the loading dose (H4) and then at day 1 (H24) and day 2 (H48). Twelve patients were included. Nine patients exhibited bacteremia, 5 were in septic shock, 8 were positive forStaphylococcus aureus, and 4 were positive for coagulase-negative staphylococci. The median MIC (first to third interquartile range) was 0.25 (0.24 to 0.41) mg/liter. Median plasma concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 64.4 (41.4 to 78.5) and 20.4 (12.4 to 30.4) mg/liter, 56.9 (31.4 to 80.6) and 21.7 (6.5 to 27.3) mg/liter, and 57.5 (32.2 to 85.1) and 20 (14.3 to 35.7) mg/liter. The median mediastinal concentrations of total and unbound oxacillin at H4, H24, and H48 were, respectively, 2.3 (0.7 to 25.9) and 0.9 (<0.5 to 15) mg/liter, 29.1 (19.7 to 38.2) and 12.6 (5.9 to 19.8) mg/liter, and 31.6 (14.9 to 42.9) and 17.1 (6.7 to 26.7) mg/liter. High-dose oxacillin delivered by continuous infusion is a valuable strategy to achieve our pharmacokinetic target (4× MIC) at the site of action at H24. But concerns remain in cases of higher MICs, emphasizing the need for clinicians to obtain the MICs for the bacteria and to monitor oxacillin concentrations, especially the unbound forms, at the target site.

scholarly journals Vancomycin Dosing in Critically Ill Patients: Robust Methods for Improved Continuous-Infusion Regimens

2011 ◽  
Vol 55 (6) ◽  
pp. 2704-2709 ◽  
Author(s):  
Jason A. Roberts ◽  
Fabio Silvio Taccone ◽  
Andrew A. Udy ◽  
Jean-Louis Vincent ◽  
Frédérique Jacobs ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Large Population ◽  
Total Body Weight ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Time Data

ABSTRACTDespite the development of novel antibiotics active against Gram-positive bacteria, vancomycin generally remains the first treatment, although rapidly achieving concentrations associated with maximal efficacy provides an unresolved challenge. The objective of this study was to conduct a population pharmacokinetic analysis of vancomycin in a large population of critically ill patients. This was a retrospective data collection of 206 adult septic critically ill patients who were administered vancomycin as a loading dose followed by continuous infusion. The concentration-versus-time data for vancomycin in serum was analyzed by a nonlinear mixed-effects modeling approach using NONMEM. Monte Carlo simulations were performed using the final covariate model. We found that the best population pharmacokinetic model consisted of a one-compartment linear model with combined proportional and additive residual unknown variability. The volume of distribution of vancomycin (1.5 liters/kg) was described by total body weight and clearance (4.6 liters/h) by 24-hour urinary creatinine clearance (CrCl), normalized to body surface area. Simulation data showed that a 35-mg/kg loading dose was necessary to rapidly achieve vancomycin concentrations of 20 mg/liter. Daily vancomycin requirements were dependent on CrCl, such that a patient with a CrCl of 100 ml/min/1.73 m2would require at least 35 mg/kg per day by continuous infusion to maintain target concentrations. In conclusion, we have found that higher-than-recommended loading and daily doses of vancomycin seem to be necessary to rapidly achieve therapeutic serum concentrations in these patients.

scholarly journals The Effect of Intraoperative Magnesium Sulphate Infusion on Emergence Agitation after Ambulatory Ophthalmic Surgery in Children

2020 ◽  
Vol 9 (12) ◽  
pp. 4126
Author(s):  
Yea-Ji Lee ◽  
Bo-Young Kim ◽  
Jae-Hee Park ◽  
Sae-Yeon Kim ◽  
Hee-Yeon Park ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Continuous Infusion ◽  
Magnesium Sulphate ◽  
Odds Ratio ◽  
Isotonic Saline ◽  
Control Group ◽  
Loading Dose ◽  
Emergence Agitation ◽  
Ophthalmic Surgery ◽  
Paediatric Patients

This study investigated whether intraoperative infusion of magnesium sulphate reduces the incidence of emergence agitation (EA) in paediatric patients who undergo ambulatory ophthalmic surgery using the Paediatric Anaesthesia Emergence Delirium (PAED) scale. Ninety-two paediatric patients who were scheduled for elective ophthalmic surgery were randomly allocated to two groups: control or magnesium. In the magnesium group, patients received an initial intravenous loading dose of 30 mg/kg of 10% solution of magnesium sulphate over 10 min and then a continuous infusion of 10 mg/kg×h during the surgery. In the control group, an equal volume of 0.9% isotonic saline was administered in the same way as in the magnesium group. The PAED scale was assessed at 15-min intervals until the PAED score reached below 10 at the postanaesthetic care unit. EA was defined as a PAED score of 10 or higher. Of the 86 patients recruited, 44 and 42 were allocated to the control and magnesium groups, respectively. The incidence of EA was 77.3% in the control group and 57.1% in the magnesium group (odds ratio, 0.392; 95% confidence interval, 0.154 to 0.997; p = 0.046). The intraoperative infusion of magnesium sulphate significantly reduced the incidence of EA.

scholarly journals Influence of Mechanical Ventilation on the Pharmacokinetics of Vancomycin Administered by Continuous Infusion in Critically Ill Patients

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Susanna Edith Medellín-Garibay ◽  
Silvia Romano-Moreno ◽  
Pilar Tejedor-Prado ◽  
Noelia Rubio-Álvaro ◽  
Aida Rueda-Naharro ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Creatinine Clearance ◽  
Continuous Infusion ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Stochastic Simulations ◽  
Population Pharmacokinetic

ABSTRACT Pathophysiological changes involved in drug disposition in critically ill patients should be considered in order to optimize the dosing of vancomycin administered by continuous infusion, and certain strategies must be applied to reach therapeutic targets on the first day of treatment. The aim of this study was to develop a population pharmacokinetic model of vancomycin to determine clinical covariates, including mechanical ventilation, that influence the wide variability of this antimicrobial. Plasma vancomycin concentrations from 54 critically ill patients were analyzed simultaneously by a population pharmacokinetic approach. A nomogram for dosing recommendations was developed and was internally evaluated through stochastic simulations. The plasma vancomycin concentration-versus-time data were best described by a one-compartment open model with exponential interindividual variability associated with vancomycin clearance and the volume of distribution. Residual error followed a homoscedastic trend. Creatinine clearance and body weight significantly dropped the objective function value, showing their influence on vancomycin clearance and the volume of distribution, respectively. Characterization based on the presence of mechanical ventilation demonstrated a 20% decrease in vancomycin clearance. External validation (n = 18) was performed to evaluate the predictive ability of the model; median bias and precision values were 0.7 mg/liter (95% confidence interval [CI], −0.4, 1.7) and 5.9 mg/liter (95% CI, 5.4, 6.4), respectively. A population pharmacokinetic model was developed for the administration of vancomycin by continuous infusion to critically ill patients, demonstrating the influence of creatinine clearance and mechanical ventilation on vancomycin clearance, as well as the implications for targeting dosing rates to reach the therapeutic range (20 to 30 mg/liter).

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