Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy

Carrié, C.; Delzor, Faustine; Roure, Stéphanie; Dubuisson, Vincent; Petit, Laurent; Molimard, Mathiéu; Breilh, Dominique; Biais, Matthieu

doi:10.1128/aac.02098-19

Cited by 14 publications

(26 citation statements)

References 35 publications

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“…Aminoglycosides are concentration-dependent agents and require a C max /MIC of 10 [ 61 ]. Two population pharmacokinetic studies focusing on amikacin concluded that ARC patients likely require increased dosing regimens [ 62 , 63 ]. Another pharmacokinetic modeling study in pediatric ICU patients who were administered tobramycin or gentamicin observed significantly lower median 24-h AUC (45.27 vs. 56.95 mg*h/L, p < 0.01) [ 64 ].…”

Section: Effects On Antibiotic Therapymentioning

confidence: 99%

Augmented Renal Clearance and How to Augment Antibiotic Dosing

Chen

Nicolau

2020

Antibiotics

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Augmented renal clearance (ARC) refers to the state of heightened renal filtration commonly observed in the critically ill. Its prevalence in this patient population is a consequence of the body’s natural response to serious disease, as well as the administration of fluids and pharmacologic therapies necessary to maintain sufficient blood pressure. ARC is objectively defined as a creatinine clearance of more than 130 mL/min/1.73 m2 and is thus a crucial condition to consider when administering antibiotics, many of which are cleared renally. Using conventional dosing regimens risks the possibility of subtherapeutic concentrations or clinical failure. Over the past decade, research has been conducted in patients with ARC who received a number of antibacterials frequently used in the critically ill, such as piperacillin-tazobactam or vancomycin. Strategies to contend with this condition have also been explored, though further investigations remain necessary.

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Section: Effects On Antibiotic Therapymentioning

confidence: 99%

Augmented Renal Clearance and How to Augment Antibiotic Dosing

Chen

Nicolau

2020

Antibiotics

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“…After assessing the articles for eligibility by applying the inclusion and exclusion criteria, 19 publications were selected. In total, 6, 11, and 5 PopPK models were analyzed for amikacin [16][17][18][19][20][21], gentamicin [21][22][23][24][25][26][27][28][29][30][31] and tobramycin [32][33][34], respectively (Figure 1).…”

Section: Study Selectionmentioning

confidence: 99%

“…Amikacin was mostly administered following a once-daily dosing regimen in six respective study protocols, except for one where it was unknown but it was mentioned that dosing regimen followed establishment's standards [18]. For amikacin, the actual doses administered to the study populations ranged from 23 mg/kg/day to 41 mg/kg/day.…”

Section: Study Designs and Protocolsmentioning

confidence: 99%

“…Across all aminoglycosides, the studies tested additive (n=2) [19,28], proportional (n=6) [18,22,27,[32][33][34] or mixed error (additive and proportional) (n=5) [20,[23][24][25][26] models in order to determine residual variability. As per Table S2 and Table S3 in the Supplementary Information, for amikacin, residual variability was estimated using a proportional model (n=1) [18], an additive model (n=1) [19] and a mixed model (n=1) [20]. As for gentamicin, the median (range) residual variability using a proportional model was 27.3% (20.8 -33.8) (n=2) [22, 27] [27], where as the 8 residual variability was estimated using an additive model in a single study where both gentamicin and tobramycin samples were used in the model development [28].…”

Section: Estimated Parametersmentioning

confidence: 99%

“…Other retained covariates for CL were glomerular filtration rate [24], sex, serum creatinine and age [34], usage of renal replacement therapy (intermittent hemodialysis [23] or continuous venovenous hemofiltration (CVVH) [22]) and the inverse of the final plasma creatinine concentration recorded in µmol/L before commencement of extended daily diafiltration (EDD-f) [27]. For the estimated Vd, most common retained covariates were related to weight and body size (body surface area (n=1) [16], adjusted bodyweight (n=1) [18], bodyweight (n=1) [24], ideal bodyweight (n=1) [22] and free fat mass (n=1) [34]). Other retained covariates for Vd were albumin [22] and sex [34],…”

Section: Inclusion Of Covariatesmentioning

confidence: 99%

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Aminoglycosides in the Intensive Care Unit: What's New in Population PK Modeling?

Duong¹,

Simard²,

Wang³

et al. 2021

Preprint

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Background Although aminoglycosides are often used as treatment for Gram-Negative infections, optimal dosing regimens remains unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycosides’ pharmacokinetics in this population. Objective The review provides comprehensive data on the pharmacokinetics of aminoglycosides in patients hospitalized in ICU by summarizing all published PopPK models in ICU patients for amikacin, gentamicin, and tobramycin. The objective was to determine the presence of a consensus on the structural model used, significant covariates included, and therapeutic targets considered during dosing regimen simulations. Methods A literature search was conducted from the Medline/PubMed database, using the terms: ‘amikacin’, ’gentamicin’, ’tobramycin’, ‘pharmacokinetic(s)’, nonlinear mixed effect’, population’, ‘intensive care’ and ‘critically ill’. Results Nineteen articles were retained where amikacin, gentamicin and tobramycin pharmacokinetics were described in six, eleven and five models, respectively. Two-compartment model best described amikacin and tobramycin pharmacokinetics, whereas one-compartment model majorly described gentamicin pharmacokinetics. The most recurrent significant covariates were renal clearance and bodyweight. Across all aminoglycosides, mean interindividual variability in clearance and volume of distribution were 41.6% and 22.0%, respectively. A common consensus for an optimal dosing regimen for each aminoglycoside was not reached. Conclusion This review showed models developed for amikacin, from 2015 until now and for gentamicin and tobramycin from the past decades. Despite growing challenges of external evaluation, the latter should be more considered during model development. Further research including new covariates, additional simulated dosing regimens and external validation should be considered to better understand aminoglycosides pharmacokinetics in ICU patients.

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What is New in Augmented Renal Clearance in Septic Patients?

Baptista,

Moura,

Silva

et al. 2023

Curr Infect Dis Rep

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Purpose of Review In this narrative review encompassing relevant scientific publications regarding critically ill patients in the last 5 years, we discuss key questions regarding the concept, pathophysiology, identification, epidemiology, and implications of augmented renal clearance (ARC) in the treatment of sepsis. Recent Findings Mathematical estimates of renal function show low accuracy when evaluating renal function in the intensive care unit, jeopardizing the correct dosing of antimicrobials. The description of ARC in critically ill patients in several, distant geographical areas worldwide reveals that this condition is more frequent than anticipated. Several new risk factors have been recently reported, needing future confirmation. Pathophysiology is still largely unknown; however, intact kidney physiology, inflammatory mediators, and tubular secretion seem to play a role. Several studies have demonstrated the association between ARC and subtherapeutic levels of several β-lactams, vancomycin, and fluconazole. Lately, there have been recommendations of dosage regimen adjustments for patients with ARC, namely, through increases in total daily dose or prolonged infusion for various antimicrobials. Literature is scarce describing the influence of ARC on clinical outcomes of patients receiving antibiotics, and results are contradictory. Summary Growing body of evidence supports that measured creatinine clearance based on time-defined urine output is strongly recommended for the identification of ARC and for reliable evaluation of its prevalence and risk factors. Clinicians should be alert for the need to use off-label dosing of antimicrobials in septic patients showing ARC. Concise recommendations for antibiotic dosage regimens, based on clinical data, are still needed.

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Population Pharmacokinetic Study of the Suitability of Standard Dosing Regimens of Amikacin in Critically Ill Patients with Open-Abdomen and Negative-Pressure Wound Therapy

Cited by 14 publications

References 35 publications

Augmented Renal Clearance and How to Augment Antibiotic Dosing

Augmented Renal Clearance and How to Augment Antibiotic Dosing

Aminoglycosides in the Intensive Care Unit: What's New in Population PK Modeling?

What is New in Augmented Renal Clearance in Septic Patients?

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