Dataset Information

Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

ABSTRACT: This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for the evaluated amikacin dosing guidelines together with a significant impact of albumin concentrations on efficacy and safety. For all recommended dosages evaluated, efficacy and safety criteria of amikacin dosage proposed were not achieved simultaneously in most of the clinical scenarios evaluated. Furthermore, a significant impact of albumin was identified: The higher is the albumin, (i) the higher will be the PTA for maximum concentration/minimum inhibitory concentration (Cmax/MIC), (ii) the lower will be the PTA for the time period with drug concentration exceeding MIC (T_>MIC) and (iii) the lower will be the PTA for toxicity (minimum concentration). Thus, accounting for albumin effect might be of interest for future amikacin dosing guidelines updates. In addition, AMKnom, an amikacin nomogram builder based on PKPD criteria, has been developed and is freely available to help evaluating dosing recommendations.

SUBMITTER: Perez-Blanco JS

PROVIDER: S-EPMC7919491 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

Pérez-Blanco Jonás Samuel JS Sáez Fernández Eva María EM Calvo María Victoria MV Lanao José M JM Martín-Suárez Ana A

Pharmaceutics 20210215 2

This study aimed to evaluate the potential efficacy and safety of the amikacin dosage proposed by the main guidelines and to develop an interactive nomogram, especially focused on the potential impact of albumin on initial dosage recommendation. The probability of target attainment (PTA) for each of the different dosing recommendations was calculated through stochastic simulations based on pharmacokinetic/pharmacodynamic (PKPD) criteria. Large efficacy and safety differences were observed for th ...[more]

PMID: 33672057

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Project description:ObjectivesContinuous renal replacement therapy (CRRT) is commonly employed in critically ill children and is known to affect antimicrobial pharmacokinetics. There is a lack of readily available, evidence-based antimicrobial dosing recommendations in pediatric CRRT. This study aims to quantify commonly used antimicrobial drugs in pediatric CRRT and identify gaps between contemporary literature-based dosing recommendations and those presented in a frequently used dosing reference.MethodsThe Pediatric Health Information System (PHIS) database was queried from July 1, 2018 through June 30, 2021 to identify admissions in which antimicrobials were billed on the same day as CRRT. Drugs of interest were selected if at least 10% of admission involved administration on at least one CRRT day, with additional clinically important antimicrobials selected by the authors. A comprehensive literature search was performed to identify antimicrobial pharmacokinetic (PK) studies in children for each selected drug. For identified articles, dosing recommendations were extracted and compared to those in a popular tertiary dosing reference (Lexi-Comp Online database). The level of agreement of the dosing recommendations was assessed.Results77 unique antimicrobial agents were identified amongst 812 admissions from 20 different PHIS hospitals. Fifteen antimicrobials were billed on the same day as CRRT in ≥10% of admissions, with 4 additional drugs deemed clinically relevant by the authors. Twenty PK studies were identified for these 19 drugs, and dosing recommendations were included in 8 (42.1%) of them. Seventeen agents (89.5%) had some type of CRRT-specific dosing guidance in Lexi-Comp, with only 1 directly based on a pediatric CRRT study. For the 8 agents with PK data available, Lexi-Comp recommendations matched primary literature dosing guidance in 3 (37.5%). Two (25%) lacked agreement between the Lexi-Comp and primary literature, and the remaining 3 (37.5%) had partial agreement with multiple dosing regimens suggested in the primary literature and at least one of these regimens recommended by Lexi-Comp.ConclusionSignificant gaps exist in the data supporting antimicrobial dosing recommendations for children receiving CRRT. Future studies should focus on antimicrobial dosing in pediatric CRRT, emphasizing provision of robust data from which dosing recommendations can be promptly incorporated into tertiary dosing references.

Project description:BackgroundDrug therapy in pediatric patients is a complex process. Children are subject to continuous growth and variation in drug-metabolizing enzyme activity, requiring continuous adaption of dosages. In Germany, currently no publicly available database exists that provides evidence-based information on drug dosages in pediatrics. For local drug dosing support, a prototype database has been developed within the Children's Hospital, Erlangen. A user-centered development process was initiated to establish an online platform for evidence-based dosing recommendations, as well as pharmacological and pharmaceutical drug information in pediatrics.ObjectivesThe objectives of the study were to survey the demand for such a platform and to assess the usability of the different versions of the developed system.MethodsThe developed prototype was evaluated in a pluralistic walkthrough with prospective end users. After a redesign, the second prototype of the online platform underwent an online usability testing based on a tailored questionnaire and the System Usability Scale (SUS) (n = 12).ResultsEleven of 12 participants expressed a demand for an online platform for pediatric dosing recommendations. The majority of the participants requested the integration of extended features, such as drug-drug interaction alerts, or information on adverse effects, pharmacokinetics, and pharmacodynamics. Particularly noteworthy is the demand for an online calculator; 5 of a total of 15 participants explicitly requested a calculator for dosages (based on age, weight, body surface) and glomerular filtration rate. The usability of the second prototype was rated "good to excellent" with a median SUS of 81.25.ConclusionLocal domain experts demand an online platform for pediatric dosing recommendations. The application of the user-centered design approach enabled the development of a prototype suitable for practical use. Multiple additional required functionalities have been identified, whereby the importance of an online calculator for patient-individual dosing recommendations was particularly emphasized.

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Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

Publications

Evaluation of Current Amikacin Dosing Recommendations and Development of an Interactive Nomogram: The Role of Albumin.

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