Implication of Haemodiafiltration Flow Rate on Amikacin Pharmacokinetic Parameters in Critically Ill Patients

Ruiz-Ramos, Jesús; Villarreal, Esther; Gordón, Mónica; Martin-Cerezula, María; Porcar, Manel; Marqués, María Remedios; Poveda, José Luís; Castellanos-Ortega, Álvaro; Ramírez, Paula

doi:10.1159/000478969

Cited by 3 publications

(2 citation statements)

References 36 publications

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“…Cmax/MIC values of $8-10 has been suggested as clinical PK/PD targets for efficacy. [172][173][174][175] Cmin of .5 mg/L for amikacin and 0.5 mg/L for gentamicin, netilmicin, and tobramycin is considered a predictor of nephrotoxicity. 172 Once daily administration is recommended to best accommodate both efficacy and safety targets.…”

Section: Aminoglycosidesmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

Matusik

Boidin

Friggeri

et al. 2022

Therapeutic Drug Monitoring

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Purpose: Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM.Methods: Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines.Results: In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes.Conclusions: Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.

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Section: Aminoglycosidesmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

Matusik

Boidin

Friggeri

et al. 2022

Therapeutic Drug Monitoring

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“…CRRT can contribute to alteration of antimicrobial PK in critically ill patients, and the amount of change should be addressed with specific studies [ 84 , 85 , 86 , 87 ]. There are different modalities of CRRT and there is not one sole indication that should be adopted to optimize antibiotic dosing.…”

Section: What Can Be Done For Icu Septic Patients In Order To Applmentioning

confidence: 99%

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

2020

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The containment of the phenomenon of resistance towards antimicrobials is a priority, especially in preserving molecules acting against Gram-negative pathogens, which represent the isolates more frequently found in the fragile population of patients admitted to Intensive Care Units. Antimicrobial therapy aims to prevent resistance through several actions, which are collectively known as “antimicrobial stewardship”, to be taken together, including the application of pharmacokinetic/pharmacodynamic (PK/PD) principles. PK/PD application has been shown to prevent the emergence of resistance in numerous experimental studies, although a straight translation to the clinical setting is not possible. Individualized antibiotic dosing and duration should be pursued in all patients, and even more especially when treating intensive care unit (ICU) septic patients in whom optimal exposure is both difficult to achieve and necessary. In this review, we report on the available data that support the application of PK/PD parameters to contain the development of resistance and we give some practical suggestions that can help to translate the benefit of PK/PD application to the bedside.

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Population pharmacokinetic/pharmacodynamic evaluations of amikacin dosing in critically ill patients undergoing continuous venovenous hemodiafiltration

Zhu

Xie

2023

Journal of Pharmacy and Pharmacology

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Objectives The pharmacokinetics/pharmacodynamics (PK/PD) of amikacin in critically ill patients undergoing continuous venovenous hemodiafiltration (CVVHDF) are poorly described, and appropriate dosing is unclear in this patient population. This study aimed to develop a population PK model of amikacin and to provide systemic PK/PD evaluations for different dosing regimens in CVVHDF patients. Methods One hundred and sixty-one amikacin concentration observations from thirty-three CVVHDF patients were pooled to develop the population PK model. Monte Carlo simulations were performed to assess the PK/PD index-based efficacy (Cmax/minimal inhibitory concentration (MIC) > 8 and AUC/MIC > 58.3), nonrisk of drug resistance (T>MIC > 60%) and risk of toxicity (trough concentration > 5 mg/l) for different dosing regimens. Key findings A two-compartment model adequately described the concentration data of amikacin. A loading dose of at least 25 mg/kg amikacin is needed to reach the efficacy targets in CVVHDF patients for an MIC of 4 mg/l, and the studied doses could not provide adequate drug exposure and T>MIC > 60% for an MIC ≥ 8 mg/l. The risk of toxicity for amikacin was unacceptably high for the patient population with low clearance. Conclusions Our study demonstrated that a loading dose of 25–30 mg/kg amikacin is needed to provide adequate PK/PD target attainment in CVVHDF patients for an MIC ≤ 4 mg/l.

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Implication of Haemodiafiltration Flow Rate on Amikacin Pharmacokinetic Parameters in Critically Ill Patients

Cited by 3 publications

References 36 publications

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review

Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting—Focus on ICU Patients and Gram-Negative Strains

Population pharmacokinetic/pharmacodynamic evaluations of amikacin dosing in critically ill patients undergoing continuous venovenous hemodiafiltration

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