Vancomycin Therapeutic Drug Monitoring Research Articles

Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population.

Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance. This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting. The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles-Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model. Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were -4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily. Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.

Impact Of Pharmacist Led Therapeutic Drug Monitoring of Vancomycin in Pediatric Cancer Patients

Aim This study aimed to evaluate the dosing regimen and therapeutic drug monitoring of vancomycin in this patient population. Method The study included 100 pediatric patients (3 months to 15 years) with various gram-positive bacterial infections. All patients received the initial vancomycin dose of 15 mg/kg every 6 hours. The researchers evaluated the incidence of achieving desired trough levels with this dosing regimen. Results The results revealed that patients between 1.0 and 5.9 years of age were less likely to achieve the desired trough levels with the initial vancomycin dose. Consequently, dose adjustments were made for patients with sub-therapeutic trough levels. These adjustments involved a 25% increase in the vancomycin dose. Importantly, the study found that the higher vancomycin dosing did not have any harmful effects on kidney function in pediatric patients, and no significant adverse effects were observed. Conclusion The dosing regimen of 15 mg/kg every 6 hours was unlikely to achieve the desired trough concentrations in pediatric patients with complicated infections and oncological diseases. The study recommends dose adjustments for the treatment of different infections in this population to increase the likelihood of reaching therapeutic steady-state concentrations of vancomycin.

Therapeutic drug monitoring of vancomycin in the real-world clinical practice of treating patients with deep suppuration after hip arthroplasty

Therapeutic drug monitoring of vancomycin in the real-world clinical practice of treating patients with deep suppuration after hip arthroplasty

Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients.

Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.

Therapeutic drug monitoring of vancomycin in surgical patients using a validated HPLC method.

Vancomycin is being used for the treatment of a variety of infections caused by methicillin resistant Staphylococcus aureus and methicillin susceptible Staphylococcus aureus. Therapeutic drug monitoring (TDM) is highly recommended for ensuring the safe and effective therapy with vancomycin. A reliable and cost-effective bioanalytical method is required for TDM as well as pharmacokinetic studies of vancomycin. A selective, sensitive, and cost effective HPLC method was developed and validated for quantification of vancomycin concentrations in human plasma. The mobile phase was a mixture of buffer (50 mM ammonium dihydrogen phosphate, pH 2.4) and acetonitrile 88 : 12 v/v. The separation was carried on C18 column (125 × 4.6 mm, particle size 5 µm) with isocratic flow rate of 0.370 mL/min at room temperature with UV detection at 215 nm. The method was validated for sensitivity, accuracy, and precision as well as stability of vancomycin in human plasma by following European Medicine Agency (EMA) guideline. Therapeutic drug monitoring of vancomycin was performed by quantifying the trough concentrations of vancomycin in 65 human plasma samples after administration of therapeutically relevant dose. The developed method was sensitive enough to quantify vancomycin concentrations as low as 0.25 mg/L in human plasma. Moreover, the method was proved accurate and precise in terms of quantifying the unknown concentration of vancomycin. The evaluation of short-term, long-term, and freeze-thaw stability proved the stability of vancomycin in human plasma. The TDM of vancomycin by using this method showed that 39 (60%) samples were within the target trough concentration range (TTCR), i.e. 10 - 20 mg/L, while 23 samples (35.4%) were below the TTCR, and 3 samples (4.6%) were above this range. The developed method is sensitive and cost effective for quantification of vancomycin in human plasma. The results of sample analysis shows that the developed method can be used reliably for TDM of vancomycin.

A Deep Learning-Based Approach for Prediction of Vancomycin Treatment Monitoring: Retrospective Study Among Patients With Critical Illness.

Vancomycin pharmacokinetics are highly variable in patients with critical illnesses, and clinicians commonly use population pharmacokinetic (PPK) models based on a Bayesian approach to dose. However, these models are population-dependent, may only sometimes meet the needs of individual patients, and are only used by experienced clinicians as a reference for making treatment decisions. To assist real-world clinicians, we developed a deep learning-based decision-making system that predicts vancomycin therapeutic drug monitoring (TDM) levels in patients in intensive care unit. This study aimed to establish joint multilayer perceptron (JointMLP), a new deep-learning model for predicting vancomycin TDM levels, and compare its performance with the PPK models, extreme gradient boosting (XGBoost), and TabNet. We used a 977-case data set split into training and testing groups in a 9:1 ratio. We performed external validation of the model using 1429 cases from Kangwon National University Hospital and 2394 cases from the Medical Information Mart for Intensive Care-IV (MIMIC-IV). In addition, we performed 10-fold cross-validation on the internal training data set and calculated the 95% CIs using the metric. Finally, we evaluated the generalization ability of the JointMLP model using the MIMIC-IV data set. Our JointMLP model outperformed other models in predicting vancomycin TDM levels in internal and external data sets. Compared to PPK, the JointMLP model improved predictive power by up to 31% (mean absolute error [MAE] 6.68 vs 5.11) on the internal data set and 81% (MAE 11.87 vs 6.56) on the external data set. In addition, the JointMLP model significantly outperforms XGBoost and TabNet, with a 13% (MAE 5.75 vs 5.11) and 14% (MAE 5.85 vs 5.11) improvement in predictive accuracy on the inner data set, respectively. On both the internal and external data sets, our JointMLP model performed well compared to XGBoost and TabNet, achieving prediction accuracy improvements of 34% and 14%, respectively. Additionally, our JointMLP model showed higher robustness to outlier data than the other models, as evidenced by its higher root mean squared error performance across all data sets. The mean errors and variances of the JointMLP model were close to zero and smaller than those of the PPK model in internal and external data sets. Our JointMLP approach can help optimize treatment outcomes in patients with critical illnesses in an intensive care unit setting, reducing side effects associated with suboptimal vancomycin administration. These include increased risk of bacterial resistance, extended hospital stays, and increased health care costs. In addition, the superior performance of our model compared to existing models highlights its potential to help real-world clinicians.

A cross-sectional study of the current situation with therapeutic drug monitoring in Thailand: Requirements, challenges and the role of educational institutions

Background: Therapeutic drug monitoring (TDM) is a drug dose determination tool for individualised therapy. Objective: This study examined the TDM services provided by hospitals and topics taught in pharmacy schools in Thailand. Methods: TDM service and curriculum questionnaires were sent to 179 hospitals and all 19 pharmacy schools in Thailand. Correlations were tested using Fisher’s exact test. Results: Completed questionnaires were returned by 116 hospitals (64.8%). Forty-three hospitals (37.1%) conducted TDM and most were large hospitals (>500 beds, n=27, 62.8%). Higher numbers of beds and pharmacists positively correlated with conducting TDM (p < 0.001 and p = 0.003, respectively). Phenytoin was the most frequently monitored drug (n=39, 90.7%). All pharmacy schools taught TDM for phenytoin, valproic acid, vancomycin, carbamazepine, and digoxin. The most frequently cited benefit of TDM was to prevent adverse drug reactions (n = 108, 93.1%). The primary reason cited for not conducting TDM was a lack of in-house laboratories (n=78, 67.2%). Conclusion: Despite a positive attitude among respondents and that TDM subjects were being taught in all pharmacy schools in Thailand, less than half of the surveyed hospitals reported conducting TDM. Providing smaller hospitals with access to the TDM laboratories and expertise at large hospitals could increase this proportion.

Optimization of therapeutic drug monitoring of vancomycin in newborns using “Dried Blood Spot” method

Therapeutic drug monitoring (TDM) is used to increase the individualization of pharmacotherapy, especially in patient groups with a high interindividual variability in pharmacokinetic (PK) parameters. One of these groups of patients is newborn children, for whom drug therapy, especially drugs with a narrow therapeutic range, causes a few difficulties or cannot be used in principle.The aim of the work was to develop and validate quantitative HPLC-MS/MS methods for the determination of vancomycin in “dried blood spot” samples using new protocols and comparison of the results obtained with the results in plasma samples using standard sample preparation methods.Materials and methods. To prepare stock and standard solutions of vancomycin and norvancomycin as an internal standard, dry portions of the corresponding certified standards of vancomycin (Servier, France) and norvancomycin (Augsburg, Germany, purity grade >95.0%) were used. A chromatographic separation of the components was carried out on a Poroshell 120 C18 column (4.6×50 mm, 2.7 µm). When developing conditions for a mass spectrometric detection of the desired substances using the multiple reaction monitoring (MRM) method, precursor ions and their corresponding product ions were determined.Results. A quantitative HPLC-MS/MS method for the determination of vancomycin in «dried blood spot» samples was developed and validated. A comparison was made between vancomycin concentrations in «dried blood spot» samples and plasma samples. Moreover, more than 95% of the calculated average concentrations are within the limits of d-2s and d+2s, which correspond to the values of –10.2 and 12.2. That confirms the suitability of the developed method for the analysis of patient samples.Conclusion. The results obtained make it possible for us to recommend the “dried blood spot” method for therapeutic monitoring of vancomycin, additional studies of PK in this group of patients with subsequent use of this drug in newborns and pediatric patients.

Clinical application of vancomycin TDM in ventilated patients with gastrointestinal cancer: a propensity-matched analysis.

Therapeutic drug monitoring (TDM) of vancomycin is widely recommended for clinical treatment. Due to the complexity of 24-h area under the curve (AUC) guided vancomycin monitoring in clinical practice, the vancomycin trough level remains the most common and practical method. The purpose of this study was designed to investigate the differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods, and further explore the clinical application of trough-guided vancomycin monitoring in patients with gastrointestinal cancer requiring mechanical ventilation. We included a total of 78 gastrointestinal cancer patients who required mechanical ventilation due to various diseases. All patients included in this study were aged 18years or older and were treated with intravenous vancomycin therapy for more than 2days due to documented or suspected Gram-positive bacterial infections, and have at least one available vancomycin plasma concentration. First, we compared the safety and efficacies of vancomycin TDM based on different monitoring methods as trough-guided monitoring or AUC-guided monitoring. Then, based on whether the initial vancomycin concentration achieving the target trough concentration (less than 48h), patients were divided into early and delayed groups, and the clinical factors were compared between them. The primary endpoints include the incidence of new-onset acute kidney injury (AKI) or renal replacement therapy (RRT), clinical success rate and 28-day all-cause mortality. Finally, the overall relationship between trough concentration and potential covariates is screened by univariate and multivariate analysis to explore potential information covariates. The research revealed that patients with gastrointestinal cancer exhibited significantly lower initial vancomycin trough concentrations (median [interquartile range (IQR)]: 6.90[5.28-11.20] mg/L). And there were no statistically significant differences in the safety and efficacies of vancomycin TDM based on the two different monitoring methods for the primary endpoint. Moreover, base on trough-guided vancomycin monitoring, the early group demonstrated a notably shorter duration of mechanical ventilation compared with the delayed group (χ2 = 4.532; p < 0.05; Fig.2E). Propensity score weighting further confirmed that the duration of mechanical ventilation (χ2 = 6.607; p < 0.05; Fig.2F) and duration of vasoactive agent (χ2 = 6.106; p < 0.05; Fig.2D) were significantly shorter in the early group compared with delayed group. Multivariate regression analysis revealed that Cystatin C (Cys-C) was the most important variable for vancomycin target trough achievement (odds ratio, 5.274; 95% CI, 1.780 to 15.627; p = 0.003). Trough-guided vancomycin monitoring is a simple and effective marker of TDM for ventilated patients with gastrointestinal cancer. Timely achievement of target trough concentrations for vancomycin can improve partial clinical outcomes in Gram-positive bacterial infections. Cys-C level is a potentially valuable parameter for predicting the vancomycin concentration.

Measuring and improving the timeliness of vancomycin therapeutic drug monitoring and potential patient safety impacts

BackgroundTimely vancomycin therapeutic drug monitoring (TDM) enables prompt dose adjustments and safe treatment. Local incidents prompted an investigation into the reasons for prolonged reporting times. ObjectivesTo investigate the variation in reporting times of vancomycin concentrations between hospitals with and without on-site TDM processing, and patient safety implications. MethodsVancomycin concentration results for Hospital 1 (off-site monitoring), Hospitals 2 and 3 (both on-site monitoring) from June to December 2021 were retrospectively analysed. Retrospective data collection was repeated for Hospital 1 three months post on-site TDM commencement for comparison. Vancomycin clinical incidents at Hospital 1 were reviewed to identify examples of when delays in reporting of results potentially contributed towards adverse patient outcomes. ResultsHospital 1 had a median reporting time of 11.13 h compared with Hospital 2 and Hospital T3 (1.73 h and 1.70 h respectively). Following the commencement of on-site TDM at Hospital 1, the reporting time reduced to 1.33 h (p < 0.001). Several incidents at Hospital 1 during the period of off-site monitoring involved delays to TDM results. ConclusionsOff-site processing of TDM introduced significant delays in reporting of vancomycin concentrations, which was significantly improved by transitioning to onsite availability of testing. This study also highlights the impact of accurate problem identification in improving patient safety.

Dried blood spot analysis for the quantification of vancomycin and creatinine using liquid chromatography – tandem mass spectrometry: Method development and validation

BackgroundVancomycin is a widely used antibiotic for the treatment of gram-positive bacterial infections, especially for methicillin-resistant Staphylococcus aureus (MRSA) infections. Due to a small therapeutic range and large inter-patient variability, therapeutic drug monitoring (TDM) of vancomycin is required to minimize toxicity and maximize treatment efficacy. Venous blood sampling is mostly applied for TDM of vancomycin, although this widely used sampling method is more invasive compared to less painful alternatives, such as the dried blood spot (DBS) method, which can be performed at home. MethodWe developed an UPLC-MS/MS method for the quantification of vancomycin and creatinine in DBS. A fast sample preparation and short analysis run time of 5.2 min were applied, which makes this method highly suitable for clinical settings. Validation was performed according to international (FDA and EMA) guidelines. ResultsThe validated concentration range was found linear for creatinine from 41.8 µmol/L to 722 µmol/L and for vancomycin from 3.8 mg/L to 76.6 mg/L (r2 > 0.990) and the inaccuracies, imprecisions, hematocrit effects, and recoveries were < 15 % for both compounds. No significant carryover effect was observed. ConclusionHence, we successfully validated a quantification method for the simultaneous determination of creatinine and vancomycin in DBS.

Therapeutic drug monitoring of vancomycin and meropenem: Illustration of the impact of inaccurate information in dose administration time

ObjectivesTo illustrate the impact of errors in documented dose administration time on therapeutic drug monitoring (TDM)-based target attainment evaluation for vancomycin and meropenem, and to explore the influence of drug and patient characteristics, and TDM sampling strategies. MethodsBedside observations of errors in documented dose administration times were collected. Population pharmacokinetic simulations were performed for vancomycin and meropenem, evaluating different one- and two-sampling strategies for populations with estimated creatinine clearance (CLcr) of 30, 80 or 130 mL/min. The impact of errors was evaluated as the proportion of individuals incorrectly considered to have reached the target. ResultsOf 143 observed dose administrations, 97% of doses were given within ±30 min of the documented time. For vancomycin, a +30 min error was predicted to result in a 0.1–3.9 percentage point increase of cases incorrectly evaluated as reaching area under the concentration-time curve during a 24-hour period (AUC24)/minimum inhibitory concentration (MIC) >400, with the largest increase for patients with augmented renal clearance and peak and trough sampling. For meropenem, a +30 min error resulted in a 1.3–6.4 and 0–20 percentage point increase of cases incorrectly evaluated as reaching 100% T>MIC, and 50% T>MIC, respectively. Overall, mid-dose and trough sampling was most favourable for both antibiotics. ConclusionsFor vancomycin, simulations indicate that TDM-based target attainment evaluation is robust with respect to the observed errors in dose administration time of ±30 min; however, the errors had a potentially clinically important impact in patients with augmented renal clearance. For meropenem, extra measures to promote correct documentation are warranted when using TDM, as the impact of errors was evident even in patients with normal renal function.

Real-Life Vancomycin Therapeutic Drug Monitoring in Coagulase-Negative Staphylococcal Bacteremia in Neonatal and Pediatric Intensive Care Unit: Are We Underestimating Augmented Renal Clearance?

Bloodstream infections (BSI) from coagulase-negative-staphylococci (CoNS) are among the most frequent healthcare-related infections. Their treatment involves the use of vancomycin, a molecule whose optimal pharmacokinetic/pharmacodynamic (PK/PD) target for efficacy and safety is an area-under-curve/minimum inhibitory concentration (AUC/MIC) ratio ≥ 400 with AUC < 600. BSIs from CoNS in pediatric and neonatal intensive care unit that occurred at the Gaslini Institute over five years were evaluated to investigate the efficacy of vancomycin therapy in terms of achieving the desired PK/PD target and determining whether any variables interfere with the achievement of this target. AUC/MIC ≥ 400 with AUC < 600 at 48 and 72 h after therapy initiation was achieved in only 21% of the neonatal population and 25% of the pediatric population. In the pediatric population, an inverse correlation emerged between estimated glomerular filtration rate (eGFR) and achieved AUC levels. Median eGFR at 72 h was significantly higher (expression of hyperfiltration) in events with AUC < 400, compared with those with AUC ≥ 400 (p < 0.001). A cut-off value of eGFR in the first 72 h has been identified (145 mL/min/1.73 m2), beyond which it is extremely unlikely to achieve an AUC ≥ 400, and therefore a higher dose or a different antibiotic should be chosen.

Evaluation Of Vancomycin Therapeutic Drug Monitoring in Intensive Care Units of a University Hospital

Introduction and aim: Therapeutic drug monitoring (TDM) of vancomycin aims to achieve an optimal response and minimize the risk of toxicity by keeping plasma levels within the therapeutic range. In this study, we aimed to evaluate the treatment and appropriateness of TDM in patients receiving vancomycin. &#x0D; Method: For this purpose, patients who received vancomycin in the ICUs of a university hospital during 8-month period between January and August 2022 were retrospectively evaluated. Demographic data, presence of renal dysfunction, length of stay, duration of treatment, dose, concomitant medications, presence of extracorporeal method, TDM, sampling time (trough and peak level) were collected. &#x0D; Results: Within the scope of the study, 213 prescriptions of 202 patients were evaluated and it was revealed that TDM was performed in 18 (8%). A total of 26 trough (n=12) and peak (n=14) level were obtained. Three (25%) of the trough and eight (57%) of the peak samples were taken at the wrong time. 50% of the trough and 64% of the peak level results were outside the reference range. TDM was not performed in 174 patients taking nephrotoxic drugs concomitantly with vancomycin. There were 84 patients who developed acute kidney injury during treatment. TDM was performed in 10 (15%) of 65 patients with pretreatment renal dysfunction. &#x0D; Conclusion: In order to minimize the risk of nephrotoxicity and to get the appropriate response, it is recommended that physicians should have a conscious approach, clinical pharmacists should take an active role and hospital pharmacists should make arrangements in the orders of patients who do not have TDM.

Association between vancomycin therapeutic drug monitoring and clinical outcomes in treating neonatal sepsis

BackgroundNeonatal sepsis is commonly treated with vancomycin in the neonatal intensive care unit. Therapeutic drug monitoring of vancomycin is routinely used to personalise dosing to optimise effectiveness and avoid toxicity. ObjectivesThis study aimed to define a target range by evaluating associations between vancomycin trough concentrations or area under the concentration time curve over 24 hours (AUC24h) and clinical outcomes in neonates. MethodsNeonates, who were admitted to the neonatal intensive care unit and received intravenous vancomycin, were included in this retrospective cohort study. For evaluating effectiveness, patients who received vancomycin for < 5 days were excluded. The AUC24h was estimated based on a study-derived population pharmacokinetic model. Primary outcomes were persistent/recurrent infections and mortality within 30 days. Secondary outcomes, including acute kidney injury (AKI), were also assessed. Logistic regression and classification and regression tree analyses were performed. ResultsA total of 448 patients (123 patients for effectiveness analysis) were included. A vancomycin trough > 10 mg/L was associated with 70% lower odds of persistent/recurrent infections (adjusted OR 0.30, 95% CI 0.09–0.86; P = 0.023). Patients who took more than a day to reach target range had 1.4 times higher odds of persistent/recurrent infections or death (P = 0.04). A vancomycin trough > 15 mg/L was associated with a three times higher risk of AKI (P = 0.003). An AUC24h of 420–650 mg*h/L was also associated with the lowest risk of composite outcomes (adjusted OR 0.29, 95% CI 0.08–0.86; P = 0.025). ConclusionA vancomycin trough target range of 10–15 mg/L and achievement of this target within a day of treatment initiation were associated with the most optimal clinical outcomes in treating neonatal sepsis.

Vancomycin Therapeutic Drug Monitoring: A Cross-Sectional Survey of Canadian Hospitals.

Little is known about the current landscape of vancomycin therapeutic drug monitoring (TDM) in Canadian hospitals, which operate within publicly funded health care systems. To determine current TDM practices for vancomycin and associated challenges and to gather perceptions about TDM based on area under the concentration-time curve (AUC) in Canadian hospitals. An electronic survey was distributed to hospital pharmacists in spring 2021 through multiple national and provincial antimicrobial stewardship, public health, and pharmacy organizations. The survey gathered data about hospital characteristics, TDM methods, inclusion criteria for patient selection, pharmacokinetic and pharmacodynamic targets, vancomycin susceptibility testing and reporting, and perceived barriers and challenges. In total, 120 pharmacists from 10 of the 13 provincial and territorial jurisdictions in Canada, representing 12.5% of Canadian acute care hospitals (n = 962), completed at least 90% of survey questions. The predominant TDM method was trough-based (107/119, 89.9%); another 10.1% of respondents (12/119) reported performing AUC-based TDM (with or without trough-based TDM), and 17.9% (19/106) of those not already using AUC-based TDM were considering implementing it within 1 to 2 years. Among hospitals performing trough-based TDM, 60.5% (66/109) targeted trough levels between 15 and 20 mg/L for serious infections with methicillin-resistant Staphylococcus aureus. One-quarter of the respondents using this method (27/109, 24.8%) agreed that trough-based TDM was of uncertain benefit, and about one-third (33/109, 30.3%) were neutral on this question. Multiple challenges were identified for trough-based TDM, including sub- or supra-therapeutic concentrations and collection of specimens at inappropriate times. Overall, 40.5% (47/116) of respondents agreed that AUC-based TDM was likely safer than trough-based TDM, whereas 23.3% (27/116) agreed that AUC-based TDM was likely more effective. This survey represents a first step in developing evidence-based, standardized best practices for vancomycin TDM that are uniquely suited to the Canadian health care system.

Evaluation of Vancomycin Area Under the Concentration-Time Curve Predictive Performance Using Bayesian Modeling Software With and Without Peak Concentration: An Academic Hospital Experience for Adult Patients Without Renal Impairment.

The revised U.S. consensus guidelines on vancomycin therapeutic drug monitoring (TDM) recommend obtaining trough and peak samples to estimate the area under the concentration-time curve (AUC) using the Bayesian approach; however, the benefit of such two-point measurements has not been demonstrated in a clinical setting. We evaluated Bayesian predictive performance with and without peak concentration data using clinical TDM data. We retrospectively analyzed 54 adult patients without renal impairment who had two serial peak and trough concentration measurements in a ≤1-week interval. The concentration and AUC values were estimated and predicted using Bayesian software (MwPharm++; Mediware, Prague, Czech Republic). The median prediction error (MDPE) for bias and median absolute prediction error (MDAPE) for imprecision were calculated based on the estimated AUC and measured trough concentration. AUC predictions using the trough concentration had an MDPE of -1.6% and an MDAPE of 12.4%, whereas those using both peak and trough concentrations had an MDPE of -6.2% and an MDAPE of 16.9%. Trough concentration predictions using the trough concentration had an MDPE of -8.7% and an MDAPE of 18.0%, whereas those using peak and trough concentrations had an MDPE of -13.2% and an MDAPE of 21.0%. The usefulness of the peak concentration for predicting the AUC on the next occasion by Bayesian modeling was not demonstrated; therefore, the practical value of peak sampling for AUC-guided dosing can be questioned. As this study was conducted in a specific setting and generalization is limited, results should be interpreted cautiously.

Evaluation of Real-World Vancomycin Dosing and Attainment of Therapeutic Drug Monitoring Targets.

In 2020, the Infectious Diseases Society of America (IDSA) recommended a change in vancomycin therapeutic drug monitoring from trough-based to AUC/MIC-based to optimize vancomycin's efficacy and reduce nephrotoxicity. Many hospitals have not implemented this change due to barriers such as the cost of AUC/MIC software and lack of provider familiarity. The purpose of this study was to determine the rate of AUC/MIC ratio target attainment using current trough-based vancomycin dosing practices at a city hospital. The rates of acute kidney injury (AKI) were also evaluated. Vancomycin orders were reviewed retrospectively to determine the expected AUC/MIC ratios using first-order pharmacokinetic equations over a 7-month period. Orders were excluded if they were written for a one-time dose, for individuals less than 18 years of age, or for those on hemodialysis. A total of 305 vancomycin orders were included in this review. Overall, 27.9% (85/305) of vancomycin orders attained the AUC/MIC ratio target of 400-600 mg·h/L as recommended by the guidelines. Nearly 35% (106/305) achieved AUC/MIC ratios below 400 mg·h/L and 37.4% (114/305) achieved AUC/MIC ratios above 600 mg·h/L. Orders for obese patients were significantly more likely to have below the target AUC/MIC ratios (68% vs. 23.9%, X2 48.48, p < 0.00001) and non-obese patients were significantly more likely to have above the target AUC/MIC ratios (45.7% vs. 12%, X2 27.36, p < 0.00001). The overall rate of acute kidney injury observed was 2.6%. Most vancomycin orders did not attain therapeutic drug monitoring targets, reflecting the ongoing clinical challenge of optimizing vancomycin doses and implementing new guideline recommendations.

Fluorimetric monitoring of vancomycin using an allosteric probe-initiated sensing platform

Vancomycin is the first-line drug for infections of methicillin-resistant Staphylococcus aureus (MRSA) and multi-drug-resistant bacteria. The effective therapeutic concentration range of vancomycin is narrow, so it's essential to implement vancomycin therapeutic drug monitoring. However, conventional detection methods have disadvantages of expensive equipment, complicated operation, or poor reproducibility. Herein, a fluorescent sensing platform initiated by an allosteric probe was constructed for simple and sensitive monitoring of vancomycin at a low cost. The key point of this platform is the well-designed allosteric probe, which comprises an aptamer and a trigger sequence. When vancomycin exists, the combination of vancomycin and the aptamer will lead to a conformational change of the allosteric probe, thus exposing the trigger sequence. The trigger can react with the molecular beacon (MB) to generate fluorescent signals. In addition, the allosteric probe combined with hybridization chain reaction (HCR) was applied to develop an amplified platform, the linear range is from 0.5 μg mL−1 to 50 μg mL−1 with the limit of detection (LOD) of 0.26 μg mL−1. Most importantly, this allosteric probe-initiated sensing platform shows good detection ability in human serum samples, and it also indicates great correlation and accuracy compared with HPLC. The present simple and sensitive allosteric probe-initiated platform has the potential to support the therapeutic drug monitoring of vancomycin, which is of great significance to promote the rational use of antibiotics in clinics.

Implementing AUC Monitoring in a Pharmacist-Managed Vancomycin Dosing Protocol: A Retrospective Cohort Study.

Consensus guidelines on the therapeutic drug monitoring of vancomycin published in 2020 recognize that using the calculated area-under-the-curve (AUC) to guide dosing maximizes clinical efficacy and minimizes risk when compared to traditional trough-based dosing. The purpose of this study was to determine whether AUC monitoring results in reduced acute kidney injury (AKI) rates in adult patients receiving vancomycin for all indications. In this study, patients 18 years or older who received pharmacist-managed vancomycin therapy were selected using pharmacy surveillance software from 2 timeframes. Patients were excluded if they received less than 48 hours of therapy or had unstable renal function or hemodialysis at baseline. The primary outcome measured was the incidence of AKI in each group of patients. Data were collected for 121 patients in each group. Concomitant nephrotoxins used in each group, as well as the sources of infection, were similar between groups. AUC monitoring did not result in a significant decrease in AKI rate (16.5% in AUC group, 14.9% in trough group; P = .61). However, patients who received AUC monitoring were more likely to be therapeutic at first follow-up compared to the trough monitoring group (43.2% in AUC group, 33.9% in trough group; P = .03). AUC monitoring also resulted in lower trough levels and total daily doses, with no difference in mortality or length of stay. AUC monitoring did not result in an observed decrease in AKI rate. Despite this, the AUC monitoring protocol was effective at reaching the goal AUC of 400-600 mg*hour/L and did not increase mortality or length of stay.