Single-dose linezolid pharmacokinetics in critically ill patients with impaired renal function especially chronic hemodialysis patients

2014 ◽  
Vol 35 (7) ◽  
pp. 405-416 ◽  
Author(s):  
Mona I. El-Assal ◽  
Sally A. Helmy
Keyword(s):  
Renal Function ◽  
Single Dose ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Impaired Renal Function ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis

scholarly journals Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Phillip J. Bergen ◽  
Jürgen B. Bulitta ◽  
Carl M. J. Kirkpatrick ◽  
Kate E. Rogers ◽  
Megan J. McGregor ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Hollow Fiber ◽  
Critically Ill Patients ◽  
Impaired Renal Function ◽  
Infection Model ◽  
Bacterial Killing ◽  
Renal Functions ◽  
Dosing Regimens ◽  
Susceptible Populations

ABSTRACT Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A Pseudomonas aeruginosa isolate (MICmeropenem 0.25 mg/liter) was studied in the hollow-fiber infection model (inoculum ∼107.5 CFU/ml; 10 days). Pharmacokinetic profiles representing critically ill patients with augmented renal clearance (ARC), normal, or impaired renal function (creatinine clearances of 285, 120, or ∼10 ml/min, respectively) were generated for three meropenem regimens (2, 1, and 0.5 g administered as 8-hourly 30-min infusions), plus 1 g given 12 hourly with impaired renal function. The time course of total and less-susceptible populations and MICs were determined. Mechanism-based modeling (MBM) was performed using S-ADAPT. All dosing regimens across all renal functions produced similar initial bacterial killing (≤∼2.5 log10). For all regimens subjected to ARC, regrowth occurred after 7 h. For normal and impaired renal function, bacterial killing continued until 23 to 47 h; regrowth then occurred with 0.5- and 1-g regimens with normal renal function (fT >5×MIC = 56 and 69%, fC min/MIC < 2); the emergence of less-susceptible populations (≥32-fold increases in MIC) accompanied all regrowth. Bacterial counts remained suppressed across 10 days with normal (2-g 8-hourly regimen) and impaired (all regimens) renal function (fT >5×MIC ≥ 82%, fC min/MIC ≥ 2). The MBM successfully described bacterial killing and regrowth for all renal functions and regimens simultaneously. Optimized dosing regimens, including extended infusions and/or combinations, supported by MBM and Monte Carlo simulations, should be evaluated in the context of ARC to maximize bacterial killing and suppress resistance emergence.

scholarly journals Impact of administration of vancomycin or linezolid to critically ill patients with impaired renal function

2011 ◽  
Vol 30 (5) ◽  
pp. 635-643 ◽  
Author(s):  
O. Rodriguez Colomo ◽  
◽  
F. Álvarez Lerma ◽  
M.I. González Pérez ◽  
J-M. Sirvent ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Impaired Renal Function

Impact of Intravenous Administration of Voriconazole in Critically Ill Patients with Impaired Renal Function

2008 ◽  
Vol 20 (1) ◽  
pp. 93-100 ◽  
Author(s):  
F. Álvarez-Lerma ◽  
A. Allepuz-Palau ◽  
M.P. Gracia ◽  
M. Ágeles León ◽  
A. Navarro ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Intravenous Administration ◽  
Critically Ill Patients ◽  
Impaired Renal Function

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.

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