A study to explore the appropriateness of dosing regimen of vancomycin in critically ill patients in a tertiary care unit of India

Belavagi, Devaraj; Bhandari, Ritika Kondel; Shafiq, Nusrat; Gota, Vikram; Patil, Anand; Pandey, Avaneesh Kumar; Mothsara, Chakrant; Gupta, Rajesh; Sahni, Neeru; Sharma, Navneet; Ray, P.; Kumar, Virendra; Sharma, Sunil; Malhotra, Samir

doi:10.18683/germs.2022.1326

Cited by 3 publications

(2 citation statements)

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“…These works include model averaging and selection algorithms to improve predictive performance ( Uster et al, 2021 ; Heus et al, 2022 ), the application of published models for prospective validation ( Ter Heine et al, 2020 ), continuous learning approaches in pediatric patients ( Hughes et al, 2021 ), clinical decision support tools for individualized dosing in pediatric patients ( Frymoyer et al, 2020 ), application in Japanese patients ( Matsumoto et al, 2022 ), and the importance of Bayesian approaches for faster and reliable monitoring ( Aljutayli et al, 2022 ). While there are works related to MIPD in vancomycin treatment for Asian patients other than Japanese populations ( Purwonugroho et al, 2012 ; Deng et al, 2013 ; Vu et al, 2019 ; Munir et al, 2021 ; Belavagi et al, 2022 ; Wei et al, 2022 ), in the Korean population, a study has been conducted in neonatal patients only ( Lee et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Model-informed precision dosing in vancomycin treatment

Yoon,

Guk,

Lee

et al. 2023

Front. Pharmacol.

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Introduction: While vancomycin remains a widely prescribed antibiotic, it can cause ototoxicity and nephrotoxicity, both of which are concentration-associated. Overtreatment can occur when the treatment lasts for an unnecessarily long time. Using a model-informed precision dosing scheme, this study aims to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model for vancomycin to determine the optimal dosage regimen and treatment duration in order to avoid drug-induced toxicity.Methods: The data were obtained from electronic medical records of 542 patients, including 40 children, and were analyzed using NONMEM software. For PK, vancomycin concentrations were described with a two-compartment model incorporating allometry scaling.Results and discussion: This revealed that systemic clearance decreased with creatinine and blood urea nitrogen levels, history of diabetes and renal diseases, and further decreased in women. On the other hand, the central volume of distribution increased with age. For PD, C-reactive protein (CRP) plasma concentrations were described by transit compartments and were found to decrease with the presence of pneumonia. Simulations demonstrated that, given the model informed optimal doses, peak and trough concentrations as well as the area under the concentration-time curve remained within the therapeutic range, even at doses smaller than routine doses, for most patients. Additionally, CRP levels decreased more rapidly with the higher dose starting from 10 days after treatment initiation. The developed R Shiny application efficiently visualized the time courses of vancomycin and CRP concentrations, indicating its applicability in designing optimal treatment schemes simply based on visual inspection.

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Section: Introductionmentioning

confidence: 99%

Model-informed precision dosing in vancomycin treatment

Yoon,

Guk,

Lee

et al. 2023

Front. Pharmacol.

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“…Recent evidence suggests that 2-hour urinary creatinine clearnce could be a suitable substitute of 24-hour urinary creatinine clearance [25,26]. A study by Belavagi D et al, exploring vancomycin dosing in critically ill patients also found that Cockcroft-Gault formula may signi cantly underestimate the GFR in patients who had ARC and overestimates the GFR in patients with normal or decreases 8-hour CrCl, making urinary CrCl a covariate in predicting drug concentration more accurately [27]. Cockcroft-Gault equation and MDRD although simple, is highly inadequate in calculating GFR in intensive care unit set up, as it does not take into account the constantly changing volume status and renal hemodynamics.…”

Section: Introductionmentioning

confidence: 99%

Clinical Pharmacokinetics and dose optimization of anti-infectives in critical care: A narrative review

Bhandari

Rohilla

Shafiq

et al. 2023

Preprint

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Critically ill patients with infections present with considerable challenges in antimicrobial use due to multiple reasons such as pathophysiological alterations, comorbidities, supportive treatment and the pathogenicity of implicated organism. Fluid shifts, hyperdynamic state, altered renal clearance are the rapid changes which are often not considered while administering antimicrobials. Vital organ dysfunction with or without Multi–Organ Dysfunction Syndrome (MODS) often necessitates use of supportive management in the form of Ventilatory Support or Renal Replacement Therapy (RRT) to Extracorpeal Membrane Oxygenation (ECMO) to name a few. These supportive measures may have implication on PK-PD of administered antimicrobials. Certain patient parameters such as age, weight, comorbid illnesses like cystic fibrosis, burns or immunocompromised state can be important determinants of pharmacokinetics and pharmacodynamics (PK-PD) of antimicrobials. Issues such as bioavailability of the antimicrobial at the primary focus of infection need to be taken into consideration while making choice of antimicrobial(s) and deciding a dose. The critical pharmacodynamic parameters that need to be taken into account consider are disease state, altered bacterial susceptibility, pathogenicity and localization of the organism and host immunity while making decisions about optimized antimicrobial treatment in a critically ill patient with infection. The current review delves on these nuances with a focus on PK-PD for optimized use of antimicrobials in a critically ill patient.

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