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Vancomycin use, dosing and serum trough concentrations in the pediatric population: a retrospective institutional review.

ABSTRACT: Vancomycin is used primarily for Gram-positive infections. Recommended dosage regimens and targeted therapeutic levels vary between institutions.This study aims to describe therapeutic levels according to initial vancomycin doses and patient's age. A secondary objective was to evaluate appropriateness of vancomycin use in our hospital.A retrospective chart review was conducted at the Children's Hospital of Eastern Ontario. Patients included in this study were classified by age (neonates, infants, children and adolescents) and categorized into those who received vancomycin ≤5 and >5 days. Initial vancomycin dosing regimens and corresponding initial trough levels obtained were evaluated. Initial trough levels drawn in relation to the third, fourth, or fifth doses corresponding to the first course of therapy were analyzed. Acceptable trough levels ranged from 5-20 mg/L.One-hundred-and-sixty-four patients who received intravenous vancomycin in 2013 were included. Of the 229 courses of vancomycin, 190 (83%) were used 5 days or less (mean 4.9 days). Sixteen infants (88.9%) and 21 adolescents (100%), who received vancomycin empiric dosing of 60 mg/kg/day, had initial trough levels >5mg/L. However, in the children's group 20 (37.7%) did not reach levels >5 mg/L. None of vancomycin minimum inhibitory concentration (MIC) values were >1mg/L for the four patients who had infections due to methicillin-resistant Staphylococcus aureus strains.In our institution, initial empiric vancomycin dosing of 60 mg/kg/day resulted in levels ≥5mg/L in most infants and adolescents. It remains unclear why some children aged 1-12 years did not achieve these levels.

SUBMITTER: Rajon K

PROVIDER: S-EPMC5499344 | biostudies-other | 2017 Apr-Jun

REPOSITORIES: biostudies-other

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Targeting Lower Serum Trough Concentrations: A New Gentamicin Dosing Strategy for Suspected Neonatal Early-Onset Sepsis.

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| S-EPMC9901316 | biostudies-literature

Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation.

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Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing.

Project description:We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of ?400, with a maximum AUC value of 800 mg · h/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were ?18 years old with ?1 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs (P < 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter (P = 0.005), with 36%, 7%, and 6% over 15 mg/liter (P < 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4; P = 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days; P = 0.03), and reduced nephrotoxicity (8%, 0%, and 2%; P = 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days (P = 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.).

| S-EPMC5786789 | biostudies-literature

Prospective trial of a novel nomogram to achieve updated vancomycin trough concentrations.

Project description:Purpose. To determine if the use of a novel vancomycin nomogram predicts dosing regimens that achieve target trough concentrations equal to or more accurate than dosing regimens calculated using traditional pharmacokinetic calculations, evaluate the incidence of subtherapeutic and supratherapeutic troughs, and assess pharmacist's impressions of the nomogram. Methods. Prospective, open-label study in 473 patients who had a new order for vancomycin and were >18 years of age and ?120?kg. Patients were randomized to the active group, dosed using the nomogram, or to the control group, dosed using traditional pharmacokinetic calculations already in place at our institution. Results. Patients dosed via nomogram were within the appropriate trough range in 44% of cases compared to 33% in the control group (P = 0.014). Vancomycin troughs less than 10?mcg/mL were significantly decreased with the use of nomogram (P = 0.032). Incidence of supratherapeutic troughs, greater than 20?mcg/mL, was not significantly different between groups (P = 0.706), and pharmacists agreed that the nomogram was easy to use and saved their time. Conclusions. A novel vancomycin nomogram was prospectively validated and found to be more effective than traditional pharmacokinetic dosing. The nomogram is being implemented as the standard dosing protocol at our institution.

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Effects of staff education and standardizing dosing and collection times on vancomycin trough appropriateness in ward patients.

Project description:Many institutions have guidelines for initiation and monitoring, but not timing, of vancomycin.Our objective was to evaluate vancomycin trough collection appropriateness before and after an initiative to change the dosing and trough collection times in ward patients.A retrospective cohort study of ward patients from May 2014-16 who received scheduled intravenous vancomycin was performed. Nurse managers and pharmacists provided staff education. Differences between pre- and post-intervention groups were compared using student's t-test for continuous data and chi-square test for categorical data.Baseline characteristics were similar between the pre-intervention (n=124) and post-intervention (n=122) groups except for weight-based maintenance dose (15.3 mg/kg vs. 16.5 mg/kg, p=0.03) and percentage of troughs collected with morning labs (14% vs. 87%, p<0.001). Patients in the pre- and post-intervention groups received a similar frequency of loading doses (14.5% vs. 16%, p=0.68). There was no significant difference in percentage of vancomycin troughs collected appropriately at 30 (40% vs. 42%, p=0.72), 60 (57% vs. 63%, p=0.35), or 75 (60% vs. 68%, p=0.22) minutes from the scheduled time of the next dose.Staff education and standardizing collection of vancomycin troughs with morning blood collections did not affect the percentage of appropriately collected vancomycin troughs.

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Continuous Learning in Model-Informed Precision Dosing: A Case Study in Pediatric Dosing of Vancomycin.

Project description:Model-informed precision dosing (MIPD) leverages pharmacokinetic (PK) models to tailor dosing to an individual patient's needs, improving attainment of therapeutic drug exposure targets and thus potentially improving drug efficacy or reducing adverse events. However, selection of an appropriate model for supporting clinical decision making is not trivial. Error or bias in dose selection may arise if the selected model was developed in a population not fully representative of the intended MIPD population. One previously proposed approach is continuous learning, in which an initial model is used in MIPD and then updated as additional data becomes available. In this case study of pediatric vancomycin MIPD, the potential benefits of the continuous learning approach are investigated. Five previously published models were evaluated and found to perform adequately in a data set of 273 pediatric patients in the intensive care unit. Additionally, two predefined simple PK models were fitted on separate populations of 50-350 patients in an approach mimicking clinical implementation of automated continuous learning. With these continuous learning models, prediction error using population PK parameters could be reduced by 2-13% compared with previously published models. Sample sizes of at least 200 patients were found suitable for capturing the interindividual variability in vancomycin at this institution, with limited benefits of larger data sets. Although comprised mostly of trough samples, these sparsely sampled routine clinical data allowed for reasonable estimation of simulated area under the curve (AUC). Together, these findings lay the foundations for a continuous learning MIPD approach.

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Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study.

Project description:IntroductionSerum cystatin C can improve glomerular filtration rate (GFR) estimation over creatinine alone, but whether this translates into clinically relevant improvements in drug dosing is unclear.MethodsThis prospective cohort study enrolled adults receiving scheduled intravenous vancomycin while hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight, serum creatinine with the Cockcroft-Gault equation, and clinical judgment. Cystatin C was later assayed from the stored serum used for the creatinine-based dosing. Vancomycin trough prediction models were developed by using factors available at therapy initiation. Residuals from each model were used to predict the proportion of patients who would have achieved the target trough with the model compared with that observed with usual care.ResultsOf 173 patients enrolled, only 35 (20%) had a trough vancomycin level within their target range (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted vancomycin troughs than models based upon serum creatinine alone, although both were an improvement over usual care. The optimal model used estimated GFR by the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence interval 45% to 61%) target trough attainment (P <0.001 compared with the 20% with usual care).ConclusionsVancomycin dosing based on standard care with Cockcroft-Gault creatinine clearance yielded poor trough achievement. The developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could yield a 2.5-fold increase in target trough achievement compared with current clinical practice. Although this study is promising, prospective validation of this or similar cystatin C-inclusive dosing models is warranted.

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The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing.

Project description:BackgroundThis systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.MethodsWe conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).ResultsAdult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15-20 μg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality.ConclusionsWe identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

| S-EPMC7866743 | biostudies-literature

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| S-EPMC6496060 | biostudies-literature

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