Vancomycin Monitoring Research Articles

1571. Evaluation of a Single Post First Dose Vancomycin Level to Achieve a Goal Vancomycin AUC

BackgroundThe 24-hour area under the serum concentration–time curve (AUC24) is the most defensible measure to predict the effectiveness and toxicity of vancomycin. The optimal method and time point to assess and optimize AUC24, however, have yet to be determined. Measuring a trough concentration at steady state has been the traditional method of monitoring vancomycin, but trough is unreliable at estimating AUC24. More accurate methods for estimating AUC24 are paired sample analysis, or a single optimally timed sample combined with population pharmacokinetics. We wished to optimize AUC24 prior to steady state for earlier goal attainment, thereby decreasing risk of treatment failure, resistance, and/or nephrotoxicity. A single optimally timed single post first dose level may be used to estimate drug clearance and thereby AUC. Based on the post first dose concentration and a population pharmacokinetic model, clearance is calculated, and the dosing regimen can be adjusted to achieve a desired AUC24. Our institution has enabled pharmacists to obtain post first dose vancomycin levels and make early dose adjustments. The aim of this project is to monitor the accuracy of this method and the outcomes of patients who have received post first dose vancomycin levels and subsequent dose assessment/adjustment.MethodsSingle-center cohort study via electronic chart review of patients with vancomycin therapeutic dose monitoring based on post first dose vancomycin levels obtained between January 2019 and April 2019.Results41 patients were dosed and monitored based on post first dose vancomycin levels. Fourteen patients (34%) required dose adjustments based on the post first dose level. Accuracy of assessment was determined in 15 patients (37%) via a steady-state level used to measure vancomycin clearance and AUC24. At steady-state following dose assessment 14/15 (93%) patients had desired targeted goal AUC24. Only two patients (5%) had greater than a 50% increase in baseline serum creatinine.ConclusionPost first dose-level analysis resulted in dose regimen modifications in one-third of patients. This consistently allowed the attainment of goal AUC24 at steady-state.Disclosures All authors: No reported disclosures.

Automating Vancomycin Monitoring to Improve Patient Safety

Intravenous vancomycin is a frequently used antibiotic and a common cause of medication-related harm because of its narrow therapeutic range. Improving monitoring of drug levels with automation in the electronic health record (EHR) may decrease this harm. After examining the existing state of vancomycin ordering, administration, and monitoring, an automated process was created in the EHR that, on initiation of a new vancomycin order, automatically ordered a vancomycin trough level 30 minutes before the fourth dose. In addition, a nursing alert was integrated into the bar coding medication administration process that, if no trough level had been drawn by the time of the administration of the fourth dose, prompted the nurse to draw a trough level. Data from a three-month, post-implementation period was compared to data from a preceding three-month period. The frequency of trough levels drawn between the third and fourth dose increased from 58.6% to 75.8% (p < 0.01). However, the percentage of trough levels drawn within one hour of the fourth dose remained unchanged, possibly because nursing staff waited for the result of the level prior to administering the next dose of vancomycin. A minority of patients in both groups had trough levels that were in range (difference between groups, p = 0.46). Automation of vancomycin monitoring was associated with improvement in the frequency of monitoring and only delayed medication dosing by six minutes. Because vancomycin is high risk, this type of process should be broadly implemented, and outcomes should be assessed to identify unexpected outcomes and necessary further refinements.

A Retrospective Review of the Efficiency of First-Dose Therapeutic Drug Monitoring of Gentamicin, Amikacin, and Vancomycin in the Pediatric Population.

Therapeutic drug monitoring (TDM) has become standard clinical practice for gentamicin, amikacin, and vancomycin to optimize efficacy and reduce toxicity. TDM after the first dose of antibiotic was adopted in our institution. This study aims to evaluate if target therapeutic drug concentrations could be achieved more rapidly in patients with TDM performed after the first dose of gentamicin, amikacin, or vancomycin compared to TDM at steady state. A single-center retrospective cohort study was conducted at KK Women's and Children's Hospital, Singapore. Patients aged 1 month to 18 years old who received amikacin, gentamicin, or vancomycin between October 2012 to March 2016 and had at least 2 serum drug concentrations done within the same dosing interval were included. The primary objective was to compare the time taken to achieve target serum drug concentrations between first-dose and steady-state TDM. A total of 334 patients on amikacin, 211 patients on gentamicin, and 140 patients on vancomycin were included. Using Kaplan-Meier analysis, the median number of days to optimize therapy was significantly shorter after first-dose TDM was performed for amikacin (first dose, 1.51 [95% confidence interval (CI), 1.44-1.89] days vs steady state, 2.85 [95%CI, 2.50-3.25] days; P < .01] and gentamicin (first dose, 1.66 [95%CI, 1.25-2.08] days vs steady state, 3.54 [95%CI, 2.40-4.75] days; P < .01] but not vancomycin (first dose, 1.34 [95%CI, 1.06-1.52] days vs steady state, 1.42 [95%CI, 1.26-1.59] days; P = .99]. First-dose TDM for gentamicin and amikacin resulted in faster attainment of target serum concentrations but did not for vancomycin. Further validation of its impact on actual clinical outcomes may be required.

In vitro evaluation of an intravenous microdialysis catheter for therapeutic drug monitoring of gentamicin and vancomycin.

A central venous catheter with a built‐in microdialysis membrane is available for continuous lactate and glucose monitoring in the intensive care unit (ICU). As this catheter might also be suitable for repeated measurements of unbound drug levels, we studied in vitro the feasibility of monitoring unbound antibiotic concentrations. The catheter was placed in various media at 37°C spiked with gentamicin or vancomycin. Dialysate fractions were repeatedly collected over 3 hours with a NaCl 0.9% perfusate flow of 5 μL/min. Total and unbound drug concentrations in medium and perfusate were measured by immunoassay. After 60 minutes stable recovery for both drugs was observed, with mean ±SD relative recoveries of vancomycin and gentamicin in human serum of 64% ±0.4% and 73% ±3%. The recoveries of the unbound concentrations were 91% ±3% and 91% ±4%. This intravenous microdialysis system may be a very useful platform for therapeutic drug monitoring in the ICU.

Probabilistic chemotherapy in knee and hip replacement infection: the place of linezolid.

Prosthetic joint infection (PJI) can occur with a wide range of microorganisms and clinical features. After replacement surgery of prosthetic joint, prescription of probabilistic broad-spectrum antimicrobial therapy is usual, while awaiting microbial culture results. The aim of our study was to describe the antibiotic susceptibility of microorganisms isolated from hip and knee PJI. The data were collected to determine the best alternative to the usual combination of piperacillin-tazobactam (TZP) or cefotaxime (CTX) and vancomycin (VAN). Based on a French prospective, multicenter study, we analyzed microbiological susceptibility to antibiotics of 183 strains isolated from patients with confirmed hip or knee PJI. In vitro susceptibility was evaluated: TZP+VAN, TZP+linezolid (LZD), CTX+VAN, and CTX+LZD. We also analyzed resistance to different antibiotics commonly used as oral alternatives. Among the 183 patients with PJI, 62 (34%) had a total knee prosthesis, and 121 (66%) a hip prosthesis. The main identified bacteria were Staphylococcus aureus (32.2% of isolates), coagulase-negative staphylococci (27.3%), Enterobacteriaceae (14.2%), and Streptococcus (13.7%). Infections were polymicrobial for 28 (15.3%) patients. All combinations were highly effective: CTX+VAN, CTX+LZD, TZP+VAN, and TZP+LZD (93.4%, 94%, 98.4%, and 98.9% of all cases respectively). Use of LZD instead of VAN in combination with a broad-spectrum beta-lactam covers almost all of the bacteria isolated in PJI. This association should be considered in probabilistic chemotherapy, as it is particularly easy to use (oral administration and no vancomycin monitoring).

Falsely Elevated Vancomycin Concentrations in a Patient Not Receiving Vancomycin

Therapeutic drug monitoring (TDM) of vancomycin is commonly performed using immunoassays. This case describes falsely elevated vancomycin serum concentrations, possibly secondary to endogenous protein interference. Vancomycin was prescribed for a patient with a suspected septic knee. A blood sample for TDM was inadvertently collected before the first dose. The reported concentration was 36.1mg/L using the Roche Modular P analyzer and remained high over the next 48hours and 8months later in the absence of vancomycin therapy. Vancomycin was undetectable in the patient sample by liquid chromatography-tandem mass spectrometry. The sample was subsequently investigated for endogenous protein interference. The responsible interference was removed by polyethylene glycol precipitation and heat inactivation. Four alternative immunoassays with varying test principles measured vancomycin concentrations ranging from undetectable to 108mg/L. A glucose-6-phosphate dehydrogenase detection method was common to the two immunoassays exhibiting the greatest interference. To our knowledge, this is the first report of falsely elevated vancomycin concentrations on the Roche Modular P analyzer. Immunoassays are generally robust in facilitating TDM but are susceptible to cross-reactivity. Assay interference should be considered and laboratory professionals contacted when vancomycin levels do not correlate with clinical expectations.

A rapid and simple UPLC method for serum vancomycin determination in pediatric patients undergoing continuous infusion or intermittent infusion of vancomycin

Vancomycin is a glycopeptide antibiotic widely used against Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus. Several studies have found that in adults, continuous infusions of vancomycin showed earlier attainment of desired target drug concentrations and reduced nephrotoxicity relative to intermittent infusion. In the pediatric population, there is no consensus on the best vancomycin infusion method. The present study developed and validated a simple and cost-effective UPLC method to determine serum vancomycin levels in pediatric patients and applied it to the therapeutic drug monitoring of vancomycin in children who were treated with either continuous infusion or intermittent infusion of vancomycin. The sample preparation procedure involves only protein precipitation and filtration, and the UPLC method takes 5 min/sample. The assay was linear from 5 mg/L to 100 mg/L (R2 = 0.999). The precision and accuracy were determined at 4 concentration levels. The intraday variability (%CV) ranged from 1.23% to 6.01% (n = 6), and the interday variability ranged from 3.02% to 9.75% (n = 18). The accuracies were good and ranged from 91.21% to 112.63%. Serum vancomycin was stable at room temperature for 12 h or for 3 freeze/thaw cycles, and the processed sample was stable in an autosampler within 15.5 h.

Readiness to implement vancomycin monitoring based on area under the concentration-time curve: A cross-sectional survey of a national health consortium.

The purpose of this study was to (1) determine whether academic medical centers implemented area under the concentration-time curve (AUC)-based monitoring for vancomycin and (2) characterize perceived barriers to implementation and challenges experienced during the implementation process. A multicenter, cross-sectional electronic survey was distributed to pharmacy representatives from 124 academic medical centers within the Vizient University Health System Consortium Pharmacy Network. Seventy-eight institutions completed the survey, representing a 62.9% response rate. Most institutions were approximately 500-1,000 beds (68/78, 87.2%), and pharmacists were primarily responsible for vancomycin therapeutic drug monitoring (66/78, 84.6%) using pharmacist-driven protocols (57/78, 73.1%). Less than one fourth (18/78, 23.1%) of responding academic medical centers performed AUC-based vancomycin monitoring, and the majority (12/18, 66.7%) used 2-point pharmacokinetics, with a smaller fraction using either Bayesian software or population-based pharmacokinetics. Of the responding institutions that only perform trough-based therapeutic drug monitoring (60/78, 76.9%), most (53/60, 88.3%) did not plan to or were unsure about transitioning to AUC-based monitoring within the next year. Both the most common challenge encountered (13/18, 72.2%) for institutions performing AUC-based monitoring and the most common barrier (44/60, 73.3%) to implementation of this monitoring strategy were pharmacist and/or provider unfamiliarity. The majority of surveyed academic medical centers have not yet implemented AUC-based vancomycin monitoring, and most institutions did not plan to adopt or were unsure about adopting this monitoring strategy within the next year.

Pharmacokinetic Monitoring of Vancomycin in Cystic Fibrosis

A correlation between vancomycin (VAN) trough concentrations (VTC) and area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) has not been established in children/adolescents with cystic fibrosis (CF). The primary objective of this study was to determine the correlation between measured VTCs and AUC/MIC using population-based pharmacokinetics. A retrospective cohort study of children/adolescents diagnosed with CF, 6 to <18 years of age, treated with VAN for methicillin-resistant Staphylococcus aureus infection was conducted. The relationship between final VTCs and calculated AUC/MIC was assessed using Pearson and Spearman correlations. All tests were 2-tailed with alpha set at 0.05. Thirty children/adolescents, 7 to 17 years of age (median age 15 year; interquartile range: 9-17 years), were included. The mean final VAN dose was 58.03 ± 18.58 mg/kg/d, and the median final VTC was 12.6 (11-13.6) mg/L. The mean AUC/MIC was 355.34 ± 138.46 (Le model) versus 426.79 ± 178.92 (Stockmann model; P = 0.089). No correlation existed between VTCs and AUC/MIC using either the model by Le (r = 0.140; P = 0.461) or Stockmann (r = 0.115; P = 0.564). Using the Stockmann model, VAN dose (mg/kg/dose) was found to have a strong positive correlation with AUC (r = 0.8874; P < 0.0001) and AUC/MIC (r = 0.7877; P < 0.0001). VTCs did not correlate with AUC or AUC/MIC. Further research is needed to determine which estimate of VAN treatment efficacy is most appropriate for children and adolescents with CF infected with methicillin-resistant Staphylococcus aureus.

Therapeutic drug monitoring of vancomycin by AUCτ-MIC ratio in patients with chronic kidney disease.

In this study which was conducted in Alzahra University Hospital (Isfahan, I.R. Iran), the therapeutic drug monitoring of vancomycin focused on determining area under the concentration-time curve at dosing interval (τ) at steady state/minimum inhibitory concentration (AUCτ/MIC) was carried out in chronic kidney disease (CKD) patients. The study population was selected from patients with the history of CKD (stages 3 or 4) treated by intravenous vancomycin. To determine vancomycin AUCτ, blood samples were taken at four different occasions (trough-1, peak, random, trough-2) between the fourth and fifth doses of vancomycin. Drug concentration was determined by fluorescence polarization technique, and the E-TEST technique was used to determine the MIC. Nineteen patients were included. For 8 (42%), 7 (37%), and 4 (21%) patients, trough concentration levels were found to be less than 10 mg/L, 10-20 mg/L, and more than 20 mg/L, respectively. The mean value of AUCτ for studied patients was 470.7 ± 228.3 mg.h/L and the mean MIC values was 1.04 ± 0.43 mg/L. Ten patients (53%) and 9 patients (47%) had the AUCτ/MIC ratios above 400 and below 400, respectively, with the average of 519.4 ± 391.3 h. Vancomycin dosing based on patient glomerular filtration rate (GFR), as a traditional method, is not accurate enough to gain the most desired vancomycin concentration in patients with decreased or changing kidney function. Measuring drug concentration and observing its therapeutic effects accordingly is inevitable in susceptible populations receiving vital drugs such as vancomycin.

AUC-Based Monitoring of Vancomycin: Closing the Therapeutic Window.

Therapeutic drug monitoring for vancomycin is in the midst of a paradigm shift from targeting trough concentrations to area under the concentration–time curve (AUC)2. The 2009 consensus review of vancomycin therapeutic drug monitoring recommended targeting trough concentrations of 15–20 mg/L to “improve tissue penetration, increase probability of obtaining optimal target serum concentrations, and improve clinical outcomes” (1). This was a level IIIB recommendation based almost entirely on expert opinion, as previous studies had demonstrated that troughs were not associated with efficacy (2). However, studies had demonstrated that trough concentrations, especially those ≥15 mg/L, were a reliable marker of increased risk of vancomycin-associated nephrotoxicity (2, 3). Conversely, AUC values and AUC/minimum inhibitory concentration (MIC) ratios had been associated with clinical efficacy (4), but no definitive upper threshold for nephrotoxicity had been established. This discordance between guideline recommendations and current literature caused a clinical dilemma, as it was known that trough concentrations have …

Prospective evaluation of vancomycin therapeutic usage and trough levels monitoring.

Vancomycin is the cornerstone of parenteral therapy for serious methicillin resistant Staphylococcus aureus infections. Optimal dosing of vancomycin is patient specific due to its narrow therapeutic window. The objective of this study is to evaluate the appropriate use of vancomycin focusing on the indication, dose, and therapeutic level monitoring. A prospective observational study was conducted in a tertiary care hospital over a 3- month period. A data collection form was used to gather information on 93 patients receiving vancomycin. Study outcomes were assessment of the appropriateness of vancomycin indication, dose, and therapeutic trough level. The use of vancomycin both empirically and after culture results was appropriate in 78.5 % of the patients. More than half of the patients (51.6 %) were given an inappropriate dose of vancomycin per actual body weight, creatinine clearance, and indication. Regarding therapeutic vancomycin monitoring, 69.0 % had inappropriate trough level monitoring. Only 15.7 % of the 166 measured troughs were within the target therapeutic level for the corresponding indication. This study demonstrates the high level of inappropriate use of vancomycin. This is mainly attributed to inappropriate dose and trough level monitoring. Interventions to improve vancomycin prescribing and monitoring practices are needed. The presence of an interdisciplinary team may improve the appropriate use of medications with a narrow therapeutic index such as vancomycin.

1391. Vancomycin Area Under the Curve (AUC) to Predict Nephrotoxicity: A Systematic Review and Meta-Analysis of Observational Studies

BackgroundRecent studies have proposed monitoring vancomycin area under the curve (AUC) as a more precise method of attaining goal exposures compared with trough monitoring. Different dosing methods and different exposure-toxicity thresholds have been proposed. Therefore, we aimed to analyze the relationship between vancomycin AUC and nephrotoxicity reported across recent studies.MethodsA systematic review of Pubmed, Medline, Scopus and compiled references was conducted. We included randomized, cohorts and case–control studies that reported vancomycin AUCs and risk of nephrotoxicity from (January 1, 1990 to January 31, 2018). The primary outcome was nephrotoxicity, defined as an increase in serum creatinine of ≥0.5 mg/L or a 50% increase from baseline on two or more consecutive measurements. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Subset analyses were conducted when possible on the impact of AUC0-24 hours and AUC24-48 hoursr exposures and AUC vs. trough guided dosing on the outcome of nephrotoxicity. AUC nephrotoxicity thresholds ranged between 550 and 700 mg hour/L. We grouped values according to lower (i.e., <650) or higher average AUC, with a threshold value of ≥650 mg hour/L defining higher AUC based on a recent prospective trial.ResultsWe identified eight eligible observational studies with a total of 2,491 patients. Of those, five studies reported AUC0-24 associated with nephrotoxicity, two studies reported AUC24-48, and two studies reported nephrotoxicity associated with AUC vs. trough-guided dosing. No RCTs were identified. Lower AUC0-24 values were associated with significantly reduced risk of nephrotoxicity (OR 0.36, 95% CI 0.23–0.56). In a sub-analysis of two studies, AUC24-48<650 mg hour/L was associated with significantly lower risk of nephrotoxicity (OR 0.45, 95% CI 0.27–0.75). Nephrotoxicity associated with AUC-guided dosing was significantly lower than trough-guided dosing (OR 0.68, 95% CI 0.46–0.99).ConclusionThis meta-analysis suggests that AUC0-24 lower than 650 mg hour/L may result in a decreased risk of nephrotoxicity. AUC-guided vancomycin dosing may result in less vancomycin-associated nephrotoxicity. Additional investigations into the benefit of AUC-guided dosing are warranted. Disclosures All authors: No reported disclosures.

The Benefit of Therapeutic Drug Monitoring of Vancomycin in a Respiratory ICU; A Patient with Acute Kidney Injury: A Case Report

Introduction: Vancomycin damage to the kidney is one of the severe adverse reactions. The primary objective of this study was to discuss how the clinical pharmacists should deal with the results of therapeutic drug monitoring (TDM) for Vancomycin. Case Presentation: A case of severe acute kidney injury in a 60-year-old woman receiving Vancomycin as empirical therapy is reported here. The patient was admitted to the respiratory intensive care unit (RICU) of the First Affiliated Hospital of Bengbu Medical College, China, on 15 Oct 2015. On Day 7, the steady-state serum trough concentration and peak concentration of Vancomycin were 102.2 and 111.9 μg/mL, respectively. Clinical pharmacists immediately contacted the clinicians and advised them to discontinue Vancomycin therapy as soon as possible, and the proposal was adopted. On Day 8, serum creatinine (SCr) increased to 719 μmol/L, and creatinine clearance rate (CrCl) decreased to 6 mL/min; then, the patient was given dialysis treatment. After she underwent dialysis treatment, SCr decreased to 330 μmol/L and CrCl increased to 14 mL/min on Day 19; then, the patient was discharged after she accepted the doctor’s advice to start a home-dialysis program outside the hospital. Conclusions: In this case, clinical pharmacists contacted the doctor to avoid further aggravated renal damage timely when they found a significant increase in Vancomycin concentrations. It indicates that the Vancomycin level can be used as an indirect marker of renal function as increased Vancomycin level results from and contributes to acute kidney injury.

Interventions targeting the prescribing and monitoring of vancomycin for hospitalized patients: a systematic review with meta-analysis.

PurposeVancomycin prescribing requires individualized dosing and monitoring to ensure efficacy, limit toxicity, and minimize resistance. Although there are nationally endorsed guidelines from several countries addressing the complexities of vancomycin dosing and monitoring, there is limited consideration of how to implement these recommendations effectively.MethodsWe conducted a systematic search of multiple databases to identify relevant comparative studies describing the impact of interventions of educational meetings, implementation of guidelines, and dissemination of educational material on vancomycin dosing, monitoring, and nephrotoxicity. Effect size was assessed using ORs and pooled data analyzed using forest plots to provide overall effect measures.ResultsSix studies were included. All studies included educational meetings. Two studies used implementation of guidance, educational meetings, and dissemination of educational materials, one used guidance and educational meetings, one educational meetings and dissemination of educational materials, and two used educational meetings solely. Effect sizes for individual studies were more likely to be significant for multifaceted interventions. In meta-analysis, the overall effect of interventions on outcome measures of vancomycin dosing was OR 2.50 (95% CI 1.29–4.84); P< 0.01. A higher proportion of sampling at steady-state concentration was seen following intervention (OR 1.95, 95% CI 1.26–3.02; P<0.01). Interventions had no effect on appropriate timing of trough sample (OR 2.02, 95% CI 0.72–5.72; P=0.18), attaining target concentration in patients (OR 1.50, 95% CI 0.49–4.63; P=0.48, or nephrotoxicity (OR 0.75, 95% CI 0.42–1.34; P=0.33).ConclusionMultifaceted interventions are effective overall in improving the complex task of dosing vancomycin, as well as some vancomycin-monitoring outcome measures. However, the resulting impact of these interventions on efficacy and toxicity requires further investigation. These findings may be helpful to those charged with designing implementation strategies for vancomycin guidelines or complex prescribing processes in hospitals.

Optimizing Vancomycin Monitoring in Pediatric Patients.

Several studies have reported that trough levels may not be optimal for monitoring vancomycin therapy, because of overexposure and nephrotoxicity risks. Therefore, we developed a population pharmacokinetic model to optimize vancomycin dosing and monitoring in pediatrics. Data were retrospectively collected on 76 pediatric patients 1-12 years of age, admitted to general pediatric wards or intensive care units at King Saud University Medical City, Riyadh, Saudi Arabia. The predictability of 3 methods for calculating the area under the curve (AUC) at steady state was assessed for optimum vancomycin therapy monitoring. The 3 methods were simple linear regression, Bayesian approach and the 2-sample pharmacokinetic equation method. We also used Monet Carlo simulations to evaluate the dosing of vancomycin. A 1-compartment model adequately described the data. A strong correlation occurred between the observed and predicted AUC from 0 to 24 hours (AUC0-24h) calculated using the Bayesian approach with a trough sample only or pharmacokinetic equations based on 2 measured samples (R = 0.93 and 0.92, respectively). For the simple linear regression method with a trough sample only, the predicted AUC0-24h at steady state with vancomycin trough levels of 10, 15 and 20 µg/mL were 413, 548 and 714 µg·hour/mL, respectively. The target AUC0-24h above 400 was achieved in 46% and 95% of individuals with trough values of 7-11 and 11-15 µg/mL, respectively. Monte Carlo simulations showed that 60-80 mg/kg/d doses are needed to optimize vancomycin therapy. In conclusion, targeting vancomycin trough levels above 15 µg/mL in pediatrics would overshoot the target AUC0-24h above 400 and expose them to unnecessary adverse events.

Barriers and facilitators of appropriate vancomycin use: prescribing context is key.

Audit studies reveal frequent non-compliance with dosing and monitoring guidelines for vancomycin. This study aimed to qualitatively explore the barriers and facilitators of compliance with vancomycin dosing and monitoring guidelines. Interviews were conducted with 16 prescribers in a large tertiary teaching hospital in Sydney, Australia. Questions explored knowledge, attitudes, and perceived complexities associated with vancomycin use. Interviews were analysed using thematic analysis. Prescribers reported utilising vancomycin guidelines, citing familiarity with guidelines, a positive perception of guidelines, awareness of poor guideline compliance, and assistance from specialist staff as facilitators of the uptake of guideline recommendations. Barriers existing within the prescribing environment such as the prescribing culture, a lack of time, and poor communication and coordination of therapeutic drug monitoring processes were identified as hindrances to guideline compliance. The provision of guidelines may not be sufficient in ensuring appropriate prescribing and monitoring of vancomycin when barriers relating to the prescribing environment exist. Developing interventions targeted toward these barriers, such as having dedicated phlebotomists for vancomycin blood sampling, fostering better handover processes, and educating staff on poorly understood aspects of guidelines, is likely to improve the uptake of guideline recommendations for vancomycin and other medications requiring therapeutic drug monitoring.

Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With Extracorporeal Membrane Oxygenation Support.

Determine pharmacokinetic (PK) parameters and optimal dosage of vancomycin for children on extracorporeal membrane oxygenation (ECMO). Retrospective PK study of vancomycin in pediatric patients on ECMO who received IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according to the presence of acute kidney injury (AKI) and requirement of renal replacement therapy (RRT). Data from 40 children, with a median age of 2.7 years of age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients. The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough levels were within therapeutic range in 53% of patients. After dose change, 93% of patients achieved therapeutic levels. The adjusted dose was 40 (34-60) mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1-1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7-0.9) L/kg; and half-life (t½) 6.2 (4.9-8.06) hours. In the AKI subgroup, 11 patients, the initial median dose was 40 (30-45) mg/kg/day every 8 (6-12) hours. Trough concentrations of vancomycin were within therapeutic range in 27% of patients. After dose modifications, 63% of patients achieved target trough concentration. The final adjusted dose was 20 mg/kg/day (15-30) every 12 (12-24) hours. Estimated PK parameters were Vd 1.16 (0.68-1.6) L/kg; CL 0.83 (0.38-1) mL/kg/min; and a t½ of 23.6 (16.2-31) hours. In patients without AKI or RRT, Vd of vancomycin was similar and CL was lower compared to pediatric critically ill patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours. In patients with AKI, the use of lower doses should be used.

The Impact of AUC-Based Monitoring on Pharmacist-Directed Vancomycin Dose Adjustments in Complicated Methicillin-Resistant Staphylococcus aureus Infection

Objective: This study aimed to assess the impact of area under the curve (AUC)-based vancomycin monitoring on pharmacist-initiated dose adjustments after transitioning from a trough-only to an AUC-based monitoring method at our institution. Methods: A retrospective cohort study of patients treated with vancomycin for complicated methicillin-resistant Staphylococcus aureus (MRSA) infection between November 2013 and December 2016 was conducted. The frequency of pharmacist-initiated dose adjustments was assessed for patients monitored via trough-only and AUC-based approaches for trough ranges: 10 to 14.9 mg/L and 15 to 20 mg/L. Results: Fifty patients were included: 36 in the trough-based monitoring and 14 in the AUC-based-monitoring group. The vancomycin dose was increased in 71.4% of patients when troughs were 10 to 14.9 mg/L when a trough-only approach was used and in only 25% of patients when using AUC estimation (P = .048). In the AUC group, the dose was increased only when AUC/minimum inhibitory concentration (MIC) <400; unchanged regimens had an estimated AUC/MIC ≥400. The AUC-based monitoring did not significantly increase the frequency of dose reductions when trough concentrations were 15 to 20 mg/L (AUC: 33.3% vs trough: 4.6%; P = .107). Conclusions: The AUC-based monitoring resulted in fewer patients with dose adjustments when trough levels were 10 to 14.9 mg/L. The AUC-based monitoring has the potential to reduce unnecessary vancomycin exposure and warrants further investigation.

Evaluating the Effect of a Web-Based E-Learning Tool for Health Professional Education on Clinical Vancomycin Use: Comparative Study.

BackgroundInternet-based learning for health professional education is increasing. It offers advantages over traditional learning approaches, as it enables learning to be completed at a time convenient to the user and improves access where facilities are geographically disparate. We developed and implemented the Vancomycin Interactive (VI) e-learning tool to improve knowledge on the clinical use of the antibiotic vancomycin, which is commonly used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA).ObjectiveThe aims of this study were to evaluate the effect of the VI e-learning tool on (1) survey knowledge scores and (2) clinical use of vancomycin among health professionals.MethodsWe conducted a comparative pre-post intervention study across the 14 hospitals of two health districts in New South Wales, Australia. A knowledge survey was completed by nurses, doctors, and pharmacists before and after release of a Web-based e-learning tool. Survey scores were compared with those obtained following traditional education in the form of an email intervention. Survey questions related to dosing, administration, and monitoring of vancomycin. Outcome measures were survey knowledge scores among the three health professional groups, vancomycin plasma trough levels, and vancomycin approvals recorded on a computerized clinical decision support system.ResultsSurvey response rates were low at 26.87% (577/2147) preintervention and 8.24% (177/2147) postintervention. The VI was associated with an increase in knowledge scores (maximum score=5) among nurses (median 2, IQR 1-2 to median 2, IQR 1-3; P<.001), but not among other professional groups. The comparator email intervention was associated with an increase in knowledge scores among doctors (median 3, IQR 2-4 to median 4, IQR 2-4; P=.04). Participants who referred to Web-based resources while completing the e-learning tool achieved higher overall scores than those who did not (P<.001). The e-learning tool was not shown to be significantly more effective than the comparator email in the clinical use of vancomycin, as measured by plasma levels within the therapeutic range.ConclusionsThe e-learning tool was associated with improved knowledge scores among nurses, whereas the comparator email was associated with improved scores among doctors. This implies that different strategies may be required for optimizing the effectiveness of education among different health professional groups. Low survey response rates limited conclusions regarding the tool’s effectiveness. Improvements to design and evaluation methodology may increase the likelihood of a demonstrable effect from e-learning tools in the future.