Systematic Comparison of Hospital-Wide Standard and Model-Based Therapeutic Drug Monitoring of Vancomycin in Adults.
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ABSTRACT:
SUBMITTER: Gastmans H
PROVIDER: S-EPMC9320266 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background and objectiveDespite the availability of clinical practice guidelines (CPGs) for therapeutic drug monitoring (TDM) of vancomycin, vancomycin serum concentrations still do not reach therapeutic concentrations in many patients. Thus, we sought to systematically review the quality and consistency of recommendations for an international cohort of CPGs regarding vancomycin TDM.MethodsPubMed, Embase, guidelines' websites and Google were searched for CPGs for vancomycin TDM. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREEII) instrument and data were independently extracted.ResultsTwelve guidelines were evaluated and the overall quality of guidelines for vancomycin TDM was moderate. The highest score was recorded in the domain of clarity of presentation, and the lowest score was recorded in the domain of rigor of development and stakeholder involvement. The specific recommendations for vancomycin TDM were moderately consistent and guidelines varied in trough concentration monitoring, frequency of TDM, and serum concentration targets.ConclusionThe overall guideline quality for vancomycin TDM was not optimal and effort is needed to improve guideline quality, especially in the domain of rigor of development and stakeholder involvement.
| S-EPMC4059638 | biostudies-literature
Project description:Cost-effectiveness analysis has been widely used to assess and compare the costs and benefits of a clinical service. The cost-effectiveness of vancomycin therapeutic drug monitoring (TDM) has not been studied in the elderly, who are susceptible to vancomycin-induced adverse effects. This study was performed to evaluate if vancomycin TDM is cost-effective in elderly patients in the Republic of Korea. Using the electronic medical records at a tertiary university hospital, we performed a retrospective observational study to evaluate the cost-effectiveness of vancomycin TDM in 850 elderly patients who underwent vancomycin TDM with an appropriate, recommended dosing regimen and 1094 elderly patients who did not. Cost-effectiveness variables such as clinical outcomes and medical expenses were evaluated using univariate and multivariate analyses. The TDM group spent significantly less than the non-TDM group per patient for total medical expenses (by USD 841.40) and medication expenses (by USD 16.70). However, no significant difference was noted between the TDM and non-TDM groups in clinical outcomes such as microbiological cure, prevention of nephrotoxicity, or reduced mortality, irrespective of admission to the intensive care unit. Vancomycin TDM in elderly patients was associated with economic benefits, but not with better clinical outcomes.
| S-EPMC8875716 | biostudies-literature
Project description:Background and objectiveThe necessity of therapeutic drug monitoring (TDM) for vancomycin is controversial. The objective of the current review was to evaluate the available evidence for the necessity of TDM in patients given vancomycin to treat Gram-positive infections.MethodsMedline, Embase, Web of Sciences, the Cochrane Library and two Chinese literature databases (CNKI, CBM) were searched. Randomized controlled studies and observational studies that compared the clinical outcomes of TDM groups vs. non-TDM groups were included. Two reviewers independently extracted the data. The primary outcome was clinical efficacy of therapy. Secondary outcomes included vancomycin associated nephrotoxicity, duration of vancomycin therapy, length of hospital stay, and mortality. Meta-analysis was performed using the Mantel-Haenszel fixed effect method (FEM). Odds ratios (ORs) or weighted mean differences (WMD) with 95% confidence intervals (95%CIs) were calculated for categorical and continuous outcomes, respectively.ResultsOne randomized controlled trial (RCT) and five cohort studies were included in the meta-analysis. Compared with non-TDM groups, TDM groups had significantly higher rates of clinical efficacy (OR = 2.62, 95%CI 1.34-5.11 P = 0.005) and decreased rates of nephrotoxicity (OR = 0.25, 95%CI 0.13-0.48 P<0.0001). Subgroup analyses showed that TDM group had significantly higher rates of clinical efficacy in both cohort studies subgroup (OR = 3.04, 95%CI 1.34-6.90) and in Asian population subgroup (OR = 3.04, 95%CI 1.34-6.90). TDM group had significantly decreased rates of nephrotoxicity in all subgroup. There was no significant difference in duration of vancomycin therapy (WMD = -0.40, 95%CI -2.83-2.02 P = 0.74) or length of stay (WMD = -1.01, 95%CI -7.51-5.49 P = 0.76) between TDM and non-TDM groups. Subgroup analyses showed there were no differences in duration of vancomycin therapy. Only one study reported mortality rates.ConclusionsStudies to date show that TDM significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin.
| S-EPMC3799644 | biostudies-literature
Project description:Background and objectivePharmacokinetic models can inform drug dosing of vancomycin in neonates to optimize therapy. However, the model selected needs to describe the intended population to provide appropriate dose recommendations. Our study aims to identify the population pharmacokinetic (PopPK) model(s) with the best performance to predict vancomycin exposure in neonates in our hospital.MethodsRelevant published PopPK models for vancomycin in neonates were selected based on demographics and vancomycin dosing strategy. The predictive performance of the models was evaluated in Tucuxi using a local cohort of 69 neonates. Mean absolute error (MAE), relative bias (rBias) and relative root mean square error (rRMSE) were used to quantify the accuracy and precision of the predictive performance of each model for three different approaches: a priori, a posteriori, and Bayesian forecasting for the next course of therapy based on the previous course predictions. A PopPK model was considered clinically acceptable if rBias was between ± 20 and 95% confidence intervals included zero.ResultsA total of 25 PopPK models were identified and nine were considered suitable for further evaluation. The model of De Cock et al. 2014 was the only clinically acceptable model based on a priori [MAE 0.35 mg/L, rBias 0.8 % (95% confidence interval (CI) - 7.5, 9.1%), and rRMSE 8.9%], a posteriori [MAE 0.037 mg/L, rBias - 0.23% (95% CI - 1.3, 0.88%), and rRMSE 6.02%] and Bayesian forecasting for the next courses [MAE 0.89 mg/L, rBias 5.45% (95% CI - 8.2, 19.1%), and rRMSE 38.3%) approaches.ConclusionsThe De Cock model was selected based on a comprehensive approach of model selection to individualize vancomycin dosing in our neonates.
| S-EPMC10954945 | biostudies-literature
Project description:Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ?18 years who received ?2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7?µg/mL (P?<?.001), which temporally coincided with recommendations published by the Infectious Disease Society of America that recommend targeting higher trough concentrations. Two or more abnormally low trough concentrations were accompanied by an increase in the dose 75% of the time. Similarly, ?2 abnormally high trough concentrations were followed by a decrease in the dose 35% of the time. In aggregate, these data suggest that vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen.
| S-EPMC5641452 | biostudies-literature
Project description:Bayesian therapeutic drug monitoring (TDM) software uses a reported pharmacokinetic (PK) model as prior information. Since its estimation is based on the Bayesian method, the estimation performance of TDM software can be improved using a PK model with characteristics similar to those of a patient. Therefore, we aimed to develop a classifier using machine learning (ML) to select a more suitable vancomycin PK model for TDM in a patient. In our study, nine vancomycin PK studies were selected, and a classifier was created to choose suitable models among them for patients. The classifier was trained using 900,000 virtual patients, and its performance was evaluated using 9000 and 4000 virtual patients for internal and external validation, respectively. The accuracy of the classifier ranged from 20.8% to 71.6% in the simulation scenarios. TDM using the ML classifier showed stable results compared with that using single models without the ML classifier. Based on these results, we have discussed further development of TDM using ML. In conclusion, we developed and evaluated a new method for selecting a PK model for TDM using ML. With more information, such as on additional PK model reporting and ML model improvement, this method can be further enhanced.
| S-EPMC9144093 | biostudies-literature
Project description:Late-onset sepsis in neonates can lead to significant morbidity and mortality, especially in preterm infants. Vancomycin is commonly prescribed for the treatment of Gram-positive organisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci, and ampicillin-resistant Enterococcus species in adult and pediatric patients. Currently, there is no consensus on optimal dosing and monitoring of vancomycin in neonates. Different vancomycin dosing regimens exist for neonates, but with many of these regimens, obtaining therapeutic trough concentrations can be difficult. In 2011, the Infectious Diseases Society of America recommended vancomycin trough concentrations of 15 to 20 mg/L or an AUC/MIC ratio of ≥400 for severe invasive diseases (e.g., MRSA) in adult and pediatric patients. Owing to recent reports of increased risk of nephrotoxicity associated with vancomycin trough concentrations of 15 to 20 mg/L and AUC/MIC of ≥400, a revised consensus guideline, recently published in 2020, no longer recommends monitoring vancomycin trough concentrations in adult patients. The guideline recommends an AUC/MIC of 400 to 600, which has been found to achieve clinical efficacy while reducing nephrotoxicity. However, these recommendations were derived solely from adult literature, as there are limited clinical outcomes data in pediatric and neonatal patients. Furthermore, owing to the variation of vancomycin pharmacokinetic parameters among the neonatal population, these recommendations for achieving vancomycin AUC/MIC of 400 to 600 in neonates require further investigation. This review will discuss the challenges of achieving optimal vancomycin dosing and monitoring in neonatal patients.
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Project description:The commercialization of CT-P13, an infliximab (IFX) biosimilar, has the potential to decrease health-related costs and enhance access to biological therapies. This study aimed to address the accuracy and inter-assay agreement of the CT-P13 quantification using four different assays initially developed to assess IFX.The four different methods, one in-house method and three commercially available kits, were used to quantify exogenously-spiked samples and the sera from 185 inflammatory bowel disease (IBD) patients on CT-P13 therapy.The quantification of the spiked samples unveiled a consistent and accurate behaviour of three of the tested methods, with average percentage recoveries of 90%, 102% and 109%. Results from the clinical samples demonstrated that these three assays were also highly correlated, both concerning Spearman's rank coefficients (range 0.890-0.947) and intraclass correlation coefficients (range 0.907-0.935). There were a few systematic deviations among them, but their impact in the clinical stratification of the patients using different cut-offs was minimal, particularly when these cut-offs were in the 3-4 µg/ml range, for which the strength of agreement (as assessed by the Kappa statistics that ranged from 0.732 to 0.902) was substantial to almost perfect.Our results indicate that three of the tested IFX quantification methods can be used to accurately quantify CT-P13 without any adjustments.
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Project description:The expanded availability of adalimumab products continues to widen patient access and reduce costs with substantial benefit to healthcare systems. However, the long-term success of these medicines is highly dependent on maintaining consistency in quality, safety and efficacy while minimizing any risk of divergence during life-cycle management. In recognition of this need and demand from global manufacturers, the World Health Organization (WHO) Expert Committee on Biological standardization established the WHO 1st International standard (IS) for Adalimumab (coded 17/236) in October 2019 with a defined unitage ascribed to each of the individual bioactivities evaluated in the study namely, TNF-α binding, TNF-α neutralization, complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity. For development of the IS, two candidate standards were manufactured as per WHO recommendations. Analysis of extensive datasets generated by testing of a common set of samples including the candidate standards by multiple stakeholders including regulatory agencies using their own qualified assays in a large international collaborative study showed comparable biological activity for the tested candidates for the different activities. Use of a common standard significantly decreased the variability of bioassays and improved agreement in potency estimates. Data from this study clearly supports the utility of the IS as an important tool for assuring analytical assay performance, for bioassay calibration and validation, for identifying and controlling changes in bioactivity during life-cycle management and for global harmonization of adalimumab products. In addition, in a separate multi-center study which included involvement of hospital and clinical diagnostic laboratories, the suitability of the adalimumab IS for therapeutic drug monitoring assays was examined by analysis of data from testing of a common blind coded panel of adalimumab spiked serum samples representative of the clinical scenario along with the IS and in-house standards in diverse immunoassays/platforms. Both commercially available and in-house assays that are routinely used for assessing adalimumab trough levels were included. Excellent agreement in estimates for adalimumab content in the spiked samples was observed regardless of the standard or the method with inter-laboratory variability also similar regardless of the standard employed. This data, for the first time, provides support for the extended applicability of the IS in assays in use for therapeutic drug monitoring based on the mass content of the IS. The adalimumab IS, in fulfilling clinical demand, can help toward standardizing and harmonizing clinical monitoring assays for informed clinical decisions and/or personalized treatment strategies for better patient outcomes. Collectively, a significant role for the adalimumab IS in assuring the quality, safety and efficacy of adalimumab products globally is envisaged.
| S-EPMC8082443 | biostudies-literature
Project description:The review includes studies dated 2011-2021 presenting the newest information on voriconazole (VCZ), mycophenolic acid (MPA), and vancomycin (VAN) therapeutic drug monitoring (TDM) in children. The need of TDM in pediatric patients has been emphasized by providing the information on the differences in the drugs pharmacokinetics. TDM of VCZ should be mandatory for all pediatric patients with invasive fungal infections (IFIs). Wide inter- and intrapatient variability in VCZ pharmacokinetics cause achieving and maintaining therapeutic concentration during therapy challenging in this population. Demonstrated studies showed, in most cases, VCZ plasma concentrations to be subtherapeutic, despite the updated dosages recommendations. Only repeated TDM can predict drug exposure and individualizing dosing in antifungal therapy in children. In children treated with mycophenolate mofetil (MMF), similarly as in adult patients, the role of TDM for MMF active form, MPA, has not been well established and is undergoing continued debate. Studies on the MPA TDM have been carried out in children after renal transplantation, other organ transplantation such as heart, liver, or intestine, in children after hematopoietic stem cell transplantation or cord blood transplantation, and in children with lupus, nephrotic syndrome, Henoch-Schönlein purpura, and other autoimmune diseases. MPA TDM is based on the area under the concentration-time curve; however, the proposed values differ according to the treatment indication, and other approaches such as pharmacodynamic and pharmacogenetic biomarkers have been proposed. VAN is a bactericidal agent that requires TDM to prevent an acute kidney disease. The particular group of patients is the pediatric one. For this group, the general recommendations of the dosing may not be valid due to the change of the elimination rate and volume of distribution between the subjects. The other factor is the variability among patients that concerns the free fraction of the drug. It may be caused by both the patients' population and sample preconditioning. Although VCZ, MMF, and VAN have been applied in pediatric patients for many years, there are still few issues to be solve regarding TDM of these drugs to ensure safe and effective treatment. Except for pharmacokinetic approach, pharmacodynamics and pharmacogenetics have been more often proposed for TDM.
| S-EPMC8707246 | biostudies-literature