In Outpatients Receiving Parenteral Vancomycin, Dosing Adjustments Produced by Area Under the Curve-Based and Trough-Based Monitoring Differ Only at the Extremes of the Therapeutic Trough Range
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PROVIDER: S-EPMC9898881 | biostudies-literature | 2023 Jan
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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
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
Project description: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.
| S-EPMC5499344 | biostudies-other
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.
| S-EPMC5499355 | biostudies-other
Project description:Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ?400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.
| S-EPMC5700348 | biostudies-literature
Project description:The therapeutic drug monitoring (TDM) of vancomycin (VCM) in critically ill patients often results in the estimated area being under the concentration-time curve (AUC) values that deviate from individual observations. In this study, we investigated the factors influencing the achievement of the target AUC of VCM at steady-state in critically ill patients. We retrospectively collected data from patients treated with VCM in an intensive care unit (ICU). Multivariate analysis was used to adjust for significant factors with p < 0.05 and identify new factors affecting the achievement of the target AUC at steady-state for VCM. Among the 113 patients included in this study, 72 (64%) were in the 1-point group (trough only), whereas 41 (36%) were in the 2-point group (trough/peak). The percentage of patients achieving the target AUC at the follow-up TDM evaluation was significantly higher in the two-point group. Multivariate analysis showed that being in the 2-point group and those with a 20% or more increase (or decrease) in creatinine clearance (CCr) were both significantly associated with the success rate of achieving the target AUC at the follow-up TDM. Novel findings revealed that in patients admitted to the ICU, changes in renal function were a predictor of AUC deviation, with a 20% or more increase (or decrease) in CCr being an indicator. We believe the indicators obtained in this study are simple and can be applied clinically in many facilities. If changes in renal function are anticipated, we recommend an AUC evaluation of VCM with a two-point blood collection, close monitoring of renal function, and dose adjustment based on reanalyzing the serum concentrations of VCM.
| S-EPMC10376485 | biostudies-literature
Project description:To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97 times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.
| S-EPMC4636270 | biostudies-literature
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.
| S-EPMC3791841 | biostudies-literature
Project description:BackgroundCo-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy.MethodsWe enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48-72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI.ResultsA total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] μg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] μg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients.ConclusionsA high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.
| S-EPMC8789664 | biostudies-literature
Project description:ObjectiveMelatonin has been considered to have an essential role in the pathophysiology of Alzheimer's disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn't show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits.MethodsWe enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment.ResultsIn the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort.ConclusionThis study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies.
| S-EPMC7851471 | biostudies-literature