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

2019 ◽  
Vol 50 ◽  
pp. 69-76 ◽  
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

scholarly journals Antibiotic Dosing for Critically Ill Adult Patients Receiving Intermittent Hemodialysis, Prolonged Intermittent Renal Replacement Therapy, and Continuous Renal Replacement Therapy: An Update

2019 ◽  
Vol 54 (1) ◽  
pp. 43-55 ◽  
Author(s):  
Brian M. Hoff ◽  
Jenana H. Maker ◽  
William E. Dager ◽  
Brett H. Heintz
Keyword(s):  
Renal Function ◽  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Response To Therapy ◽  
Intermittent Hemodialysis ◽  
Intermittent Renal Replacement Therapy ◽  
Antibiotic Dosing

Objective: To summarize current antibiotic dosing recommendations in critically ill patients receiving intermittent hemodialysis (IHD), prolonged intermittent renal replacement therapy (PIRRT), and continuous renal replacement therapy (CRRT), including considerations for individualizing therapy. Data Sources: A literature search of PubMed from January 2008 to May 2019 was performed to identify English-language literature in which dosing recommendations were proposed for antibiotics commonly used in critically ill patients receiving IHD, PIRRT, or CRRT. Study Selection and Data Extraction: All pertinent reviews, selected studies, and references were evaluated to ensure appropriateness for inclusion. Data Synthesis: Updated empirical dosing considerations are proposed for antibiotics in critically ill patients receiving IHD, PIRRT, and CRRT with recommendations for individualizing therapy. Relevance to Patient Care and Clinical Practice: This review defines principles for assessing renal function, identifies RRT system properties affecting drug clearance and drug properties affecting clearance during RRT, outlines pharmacokinetic and pharmacodynamic dosing considerations, reviews pertinent updates in the literature, develops updated empirical dosing recommendations, and highlights important factors for individualizing therapy in critically ill patients. Conclusions: Appropriate antimicrobial selection and dosing are vital to improve clinical outcomes. Dosing recommendations should be applied cautiously with efforts to consider local epidemiology and resistance patterns, antibiotic dosing and infusion strategies, renal replacement modalities, patient-specific considerations, severity of illness, residual renal function, comorbidities, and patient response to therapy. Recommendations provided herein are intended to serve as a guide in developing and revising therapy plans individualized to meet a patient’s needs.

Population pharmacokinetics and dosing considerations of daptomycin in critically ill patients undergoing continuous renal replacement therapy

2020 ◽  
Vol 75 (6) ◽  
pp. 1559-1566
Author(s):  
Feifan Xie ◽  
Sanwang Li ◽  
Zeneng Cheng
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
High Probability ◽  
Population Pharmacokinetic ◽  
Target Attainment ◽  
Concentration Data ◽  
Concentration Threshold

Abstract Objectives The dosing regimen of daptomycin for critically ill patients undergoing continuous renal replacement therapy (CRRT) remains controversial. The goal of this study was to provide guidance for optimal daptomycin therapy in CRRT patients with Staphylococcus aureus infections. Methods Individual concentration data of 32 CRRT subjects pooled from previously published studies were used to construct the population pharmacokinetic model for daptomycin. Model-based simulations were performed to evaluate the efficacy and risk of toxicity for daptomycin doses of 4, 6 and 8 mg/kg, q24h or q48h, under CRRT doses of 25, 30 and 35 mL/h/kg. Efficacy was assessed by the bacteriostatic and bactericidal AUC/MIC targets and drug exposure-based efficacy references. Toxicity was estimated by safety exposure references and the trough concentration threshold. Results A two-compartment model adequately described the pharmacokinetics of daptomycin. Efficacy analysis demonstrated that q48h dosing is associated with an extremely low probability of bactericidal target attainment on every second day after dosing and q24h dosing is preferred for a high probability of bactericidal target attainment. Toxicity evaluation showed that 8 mg/kg q24h has a high probability for reaching the toxicity-related concentration threshold, while 6 mg/kg q24h gives a satisfactory risk–benefit balance. The studied CRRT doses had a limited impact on efficacy and a CRRT dose of 30–35 mL/h/kg may lower the risk of toxicity. Conclusions The model predicted that the combination of 6 mg/kg q24h daptomycin dose and CRRT dose of 30–35 mL/h/kg would achieve the best balance of efficacy and safety.

scholarly journals Size Matters: The Influence of Patient Size on Antibiotics Exposure Profiles in Critically Ill Patients on Continuous Renal Replacement Therapy

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1390
Author(s):  
Soo-Min Jang ◽  
Alex R. Shaw ◽  
Bruce A. Mueller
Keyword(s):  
Monte Carlo ◽  
Renal Replacement Therapy ◽  
Monte Carlo Simulations ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Target Attainment ◽  
Patient Size ◽  
Patient Weight

(1) Purpose of this study: To determine whether patient weight influences the probability of target attainment (PTA) over 72 h of initial therapy with beta-lactam (cefepime, ceftazidime, piperacillin/tazobactam) and carbapenem (imipenem, ertapenem, meropenem) antibiotics in the critical care setting. This is the first paper to address the question of whether patient size affects antibiotic PTA in the ICU. (2) Methods: We performed a post hoc analysis of Monte Carlo simulations conducted in virtual critically ill patients receiving antibiotics and continuous renal replacement therapy. The PTA was calculated for each antibiotic on the following pharmacodynamic (PD) targets: (a) were above the target organism’s minimum inhibitory concentration (≥%fT≥1×MIC), (b) were above four times the MIC (≥%fT≥4×MIC), and (c) were always above the MIC (≥100%fT≥MIC) for the first 72 h of antibiotic therapy. The PTA was analyzed in patient weight quartiles [Q1 (lightest)-Q4 (heaviest)]. Optimal doses were defined as the lowest dose achieving ≥90% PTA. (3) Results: The PTA for fT≥1×MIC led to similarly high rates regardless of weight quartiles. Yet, patient weight influenced the PTA for higher PD targets (100%fT≥MIC and fT≥4×MIC) with commonly used beta-lactams and carbapenems. Reaching the optimal PTA was more difficult with a PD target of 100%fT≥MIC compared to fT≥4×MIC. (4) Conclusions: The Monte Carlo simulations showed patients in lower weight quartiles tended to achieve higher antibiotic pharmacodynamic target attainment compared to heavier patients.

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