Meropenem Target Attainment and Population Pharmacokinetics in Critically Ill Septic Patients with Preserved or Increased Renal Function

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.

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Pharmacokinetics of linezolid in critically ill patients on continuous renal replacement therapy: Influence of residual renal function on PK/PD target attainment

Journal of Critical Care ◽

10.1016/j.jcrc.2018.11.016 ◽

2019 ◽

Vol 50 ◽

pp. 69-76 ◽

Cited By ~ 2

Author(s):

Helena Barrasa ◽

Amaia Soraluce ◽

Arantxazu Isla ◽

Alejandro Martín ◽

Javier Maynar ◽

...

Keyword(s):

Renal Function ◽

Renal Replacement Therapy ◽

Continuous Renal Replacement Therapy ◽

Replacement Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Residual Renal Function ◽

Target Attainment

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Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-020-02873-5 ◽

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

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Therapeutic Drug Monitoring of Meropenem and Piperacillin in Critical Illness—Experience and Recommendations from One Year in Routine Clinical Practice

Antibiotics ◽

10.3390/antibiotics9030131 ◽

2020 ◽

Vol 9 (3) ◽

pp. 131

Author(s):

Christina Scharf ◽

Michael Paal ◽

Ines Schroeder ◽

Michael Vogeser ◽

Rika Draenert ◽

...

Keyword(s):

Renal Function ◽

Clinical Practice ◽

Therapeutic Drug Monitoring ◽

Critically Ill ◽

Drug Monitoring ◽

Critically Ill Patients ◽

Therapeutic Drug ◽

Beta Lactam ◽

Target Attainment ◽

Number Of Patients

Various studies have reported insufficient beta-lactam concentrations in critically ill patients. The extent to which therapeutic drug monitoring (TDM) in clinical practice can reduce insufficient antibiotic concentrations is an ongoing matter of investigation. We retrospectively evaluated routine meropenem and piperacillin measurements in critically ill patients who received antibiotics as short infusions in the first year after initiating a beta-lactam TDM program. Total trough concentrations above 8.0 mg/L for meropenem and above 22.5 mg/L for piperacillin were defined as the breakpoints for target attainment. We included 1832 meropenem samples and 636 piperacillin samples. We found that 39.3% of meropenem and 33.6% of piperacillin samples did not reach the target concentrations. We observed a clear correlation between renal function and antibiotic concentration (meropenem, r = 0.53; piperacillin, r = 0.63). Patients with renal replacement therapy or creatinine clearance (CrCl) of <70 mL/min had high rates of target attainment with the standard dosing regimens. There was a low number of patients with a CrCl >100 mL/min that achieved the target concentrations with the maximum recommended dosage. Patients with impaired renal function only required TDM if toxic side effects were noted. In contrast, patients with normal renal function required different dosage regimens and TDM-guided therapy to reach the breakpoints of target attainment.

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Population pharmacokinetics and probability of target attainment of meropenem in critically ill patients

European Journal of Clinical Pharmacology ◽

10.1007/s00228-016-2053-x ◽

2016 ◽

Vol 72 (7) ◽

pp. 839-848 ◽

Cited By ~ 23

Author(s):

Francesca Mattioli ◽

Carmen Fucile ◽

Valerio Del Bono ◽

Valeria Marini ◽

Andrea Parisini ◽

...

Keyword(s):

Population Pharmacokinetics ◽

Critically Ill ◽

Critically Ill Patients ◽

Target Attainment

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Meropenem Pharmacokinetics and Target Attainment in Critically Ill Patients Are Not Affected by Extracorporeal Membrane Oxygenation: A Matched Cohort Analysis

Microorganisms ◽

10.3390/microorganisms9061310 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1310

Author(s):

Matthias Gijsen ◽

Erwin Dreesen ◽

Pieter Annaert ◽

Johan Nicolai ◽

Yves Debaveye ◽

...

Keyword(s):

Renal Function ◽

Body Weight ◽

Extracorporeal Membrane Oxygenation ◽

Critically Ill ◽

Critically Ill Patients ◽

Matched Cohort ◽

Target Attainment ◽

Membrane Oxygenation ◽

Population Pk ◽

Dosing Intervals

Existing evidence is inconclusive whether meropenem dosing should be adjusted in patients receiving extracorporeal membrane oxygenation (ECMO). Therefore, the aim of this observational matched cohort study was to evaluate the effect of ECMO on pharmacokinetic (PK) variability and target attainment (TA) of meropenem. Patients admitted to the intensive care unit (ICU) simultaneously treated with meropenem and ECMO were eligible. Patients were matched 1:1, based on renal function and body weight, with non-ECMO ICU patients. Meropenem blood sampling was performed over one or two dosing intervals. Population PK modelling was performed using NONMEM7.5. TA was defined as free meropenem concentrations >2 or 8 mg/L (i.e., 1 or 4× minimal inhibitory concentration, respectively) throughout the whole dosing interval. In total, 25 patients were included, contributing 27 dosing intervals. The overall TA was 56% and 26% for the 2 mg/L and 8 mg/L target, respectively. Population PK modelling identified estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology equation and body weight, but not ECMO, as significant predictors. In conclusion, TA of meropenem was confirmed to be poor under standard dosing in critically ill patients but was not found to be influenced by ECMO. Future studies should focus on applying dose optimisation strategies for meropenem based on renal function, regardless of ECMO.

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