Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization

Sime, Fekade Bruck; Udy, Andrew; Roberts, Jason A.

doi:10.1016/j.coph.2015.06.002

Cited by 115 publications

(131 citation statements)

References 36 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…clearance (ARC) of antibiotics leading to subtherapeutic concentrations has been extensively described. 43 Despite increasing appreciation of this phenomenon, scarce data are available in children receiving β-lactam antibiotics. 14,40,44 In our study population clearance values higher than expected were observed in some patients with observed individual piperacillin clearances up to 0.35 L/h/kg.…”

Section: Discussionmentioning

confidence: 99%

Dose optimization of piperacillin/tazobactam in critically ill children

Cock¹,

Dijkman

Jaeger

et al. 2017

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

Running title: Paediatric piperacillin/tazobactam dose rationale SynopsisObjectives. The aim of this study was to characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.Patients and Methods. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg q6h based on piperacillin). Piperacillin/tazobactam concentrations were measured by a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic data was analysed using nonlinear mixed effects modelling.Results. Piperacillin and tazobactam blood samples were collected from 47 patients (median age: 2.83 years; range: 2 months -15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model which included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 L/h and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) q4h over 2 hours, 100 mg/kg q4h given over 1 hour or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24h were minimally required to achieve the therapeutic targets for piperacillin (60 % fT>MIC>16 mg/L). Conclusion. Standard intermittent dosing regimens do not ensure optimalpiperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.

show abstract

Section: Discussionmentioning

confidence: 99%

Dose optimization of piperacillin/tazobactam in critically ill children

Cock¹,

Dijkman

Jaeger

et al. 2017

Journal of Antimicrobial Chemotherapy

View full text Add to dashboard Cite

show abstract

“…It is noteworthy that the infusion of doripenem over 4 h in patients with augmented renal function led to more optimal antibiotic exposure in this study. Although there are conflicting results regarding the association between low or undetectable blood ␤-lactam levels and poor clinical outcomes in infected patients (27,28), the increased glomerular filtration and drug elimination caused by augmented renal function is known to predict subtherapeutic ␤-lactam concentrations (20,29). Limited data evaluating doripenem PK in patients with augmented renal function indicate a decreased PTA in such patients, which favors the use of extended infusions (16,21).…”

Section: Discussionmentioning

confidence: 99%

“…infusion over 1 h. The infusion of 500 mg every 8 h by i.v. infusion for 1 h was inappropriate for patients with augmented renal clearance (130 ml/min Յ CL CR Ͻ 170 ml/min) (20), whereas the infusion of 500 mg every 8 h by i.v. infusion over 4 h was appropriate.…”

Section: Residual Variability Was Best Explained By a Poisson Error Mmentioning

confidence: 99%

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

Lee

Kim

Jin

et al. 2017

Antimicrob Agents Chemother

View full text Add to dashboard Cite

We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n ϭ 37) with a creatinine clearance (CL CR ) of 20 to 50 ml/min or Ͼ50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CL CR . The proposed equation to estimate doripenem CL in Korean patients was CL/WT ϭ 0.109 ϫ WT ϫ (CL CR /57) 0.688 , where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was Յ1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.

show abstract

“…In septic AKI patients, renal function was reported not to decline as low as expected, which could lead to underestimation of glomerular filtration rate and insufficient drug dosing [10]. This phenomenon is termed aug- mented renal clearance in which renal function for solution clearance is elevated more than expected by visible laboratory data in critically ill patients [11,12]. Therefore, more sensitive biomarkers such as the measured creatinine clearance are needed.…”

Section: Discussionmentioning

confidence: 99%

Increased Creatinine Clearance in Acute Kidney Injury due to Heat Stroke

Urabe¹,

Kotani²,

Tsujimoto³

2018

J Med Cases

View full text Add to dashboard Cite

Acute kidney injury (AKI) is associated with increased mortality and risk of chronic kidney disease (CKD). Whereas AKI is well known to occur frequently in patients with heat stroke, creatinine clearance levels of these patients have not been evaluated in literature. In this report, we present the case of a patient with increased creatinine clearance who developed AKI due to heat stroke. A 40-year-old male with no past medical history was admitted to the intensive care unit of our hospital due to AKI from heat stroke. Although he was diagnosed with stage 3 AKI at admission, his creatinine clearance, measured by a 12-h urine collection, was highly elevated to 230 mL/min/1.73 m 2 . His serum creatinine was decreased to the baseline level 12 h after admission, with fluid resuscitation. This case can suggest that creatinine clearance might be underestimated, although serum creatinine levels are elevated in AKI due to heat stroke.

show abstract

Augmented renal clearance in critically ill patients: etiology, definition and implications for beta-lactam dose optimization

Cited by 115 publications

References 36 publications

Dose optimization of piperacillin/tazobactam in critically ill children

Dose optimization of piperacillin/tazobactam in critically ill children

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

Increased Creatinine Clearance in Acute Kidney Injury due to Heat Stroke

Contact Info

Product

Resources

About