Vancomycin Trough Research Articles

Optimization of the vancomycin administration regimen by clinical pharmacists based on a population pharmacokinetics model: a prospective interventional study

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model. Retrospectively enrolled patients constituted the control group, and prospectively enrolled patients constituted the intervention group. The vancomycin administration regimen, trough concentration, pharmacokinetic parameters, and clinical outcomes of the two groups were compared. The control and intervention groups comprised 236 and 138 patients, respectively. Compared with those in the control group, the therapeutic drug monitoring (TDM) and correct TDM sampling time rates in the intervention group were significantly higher (76.92% vs. 43.59%; 63.9% vs. 39.0%, both p < 0.001). The rates of an initial trough concentration within 10–20 mg/L and an adjusted regimen were also significantly higher in the intervention group (55.80% vs. 30.51%, 71.95% vs. 39.18%, both p < 0.001). The rate of an area under the curve (AUC) within 400–650 mg·h/L was higher in the intervention group than in the control group (52.7% vs. 36.6%, p < 0.001). The eradication rates of Gram-positive bacteria were 91.4% in the intervention group and 81.3% in the control group (p = 0.049). Eight patients developed acute kidney injury (AKI) in the control group; however, no AKI occurred in the intervention group (p = 0.029). Intervention by clinical pharmacists can increase the rate of correct sampling time. Using the PPK model combined with Bayesian estimation, clinical pharmacists can greatly increase the trough concentration and AUCs within the target range, especially for adjusted regimens. Higher PK/PD target rates resulted in better Gram-positive bacterial eradication and reduced renal toxicity of vancomycin.

Suboptimal vancomycin levels in critically ill children with sickle cell disease and acute chest syndrome

ObjectivesThis is a pilot retrospective study to assess the effect of glomerular hyper-filtration (GHF) related to sickle cell disease (SCD) on vancomycin clearance and ultimately on therapeutic drug levels in children admitted to the pediatric intensive care unit (PICU) with acute chest syndrome (ACS). MethodThe patients’ steady-state vancomycin trough levels (VTL) and the area under the curve (AUC) were compared with those of age- and gender-matched control group; matching was made at a 1:3 ratio. ResultsTwelve SCD patients with ACS and treated with vancomycin were compared with 36 non-SCD patients (control group). Compared with the control patients, the ACS patients had significantly lower initial serum VTL (median = 6.00 mcg/mL vs. 9.75 mcg/mL) (p = 0.007), and their average VTL were still lower (median = 6.65 mcg/mL vs. 10.00 mcg/mL) post vancomycin dose adjustment (p = 0.039). The time to achieve the therapeutic vancomycin level was significantly longer for the ACS patients (median = 4.75 days) than for the control group (median = 1 day) (p = 0.009). The AUC was also significantly lower in the ACS patients (median = 293 mg*h/L) than in the control group (median = 405.5 mg*h/L) (p = 0.007). The AUC was negatively associated with creatinine clearance (Beta Coefficient = −0.366, p-value=<0.001) even when adjusted for receiving loading dose, standard dose per weight, and severity of critical illness. ConclusionThese findings support the attributed role of the GHF associated with SCD leading to lower vancomycin level in ACS cases. Therefore, the standard dosing approach for vancomycin in ACS patients may be ineffective. We thus advocate for individualized dosing with careful monitoring of drug levels to account for GHF.

Prediction Accuracy of Area under the Concentration-Time Curve of Vancomycin by Bayesian Approach Using Creatinine-Based Equations of Estimated Kidney Function in Bedridden Elderly Japanese Patients.

An administration plan for vancomycin (VCM) in bedridden elderly patients has not been established. This retrospective study aimed to evaluate the prediction accuracy of the area under the concentration-time curve (AUC) of VCM by the Bayesian approach using creatinine-based equations of estimated kidney function in such patients. Kidney function was estimated using the Japanese equation of estimated glomerular filtration rate (eGFR) and the Cockcroft-Gault equation of estimated creatinine clearance (eCCr). eCCr (serum creatinine (SCr) + 0.2) was calculated by substituting the SCr level +0.2 mg/dL into the Cockcroft-Gault equation. For eGFR/0.789, eGFR, eCCr, and eCCr (SCr + 0.2), the AUC values were calculated by the Bayesian approach using the therapeutic drug monitoring (TDM) software, BMs-Pod (ver 8.06) and denoted as AUCeGFR/0.789, AUCeGFR, AUCeCCr, and AUCeCCr (SCr + 0.2) respectively. The reference AUC (AUCREF) was calculated by applying VCM's peak and trough steady-state concentrations to first-order pharmacokinetic equations. The medians (range) of AUCeGFR/0.789/AUCREF, AUCeGFR/AUCREF, AUCeCCr/AUCREF, and AUCeCCr (SCr + 0.2)/AUCREF were 0.88 (0.74-0.93), 0.90 (0.79-1.04), 0.92 (0.81-1.07), and 1.00 (0.88-1.11), respectively. Moreover, the percentage of patients within 10% of the AUCREF, defined as |Bayesian-estimated AUC - AUCREF| < AUCREF × 0.1, was the highest (86%) in AUCeCCr (SCr + 0.2). These results suggest that the Bayesian approach using eCCr (SCr + 0.2) has the highest prediction accuracy for the AUCREF in bedridden elderly patients. Although further studies are required with more accurate determination methods of the CCr and AUC, our findings highlight the potential of eCCr (SCr + 0.2) for estimating VCM's AUC by the Bayesian approach in such patients.

Effect of First Trough Vancomycin Concentration on the Occurrence of AKI in Critically Ill Patients: A Retrospective Study of the MIMIC-IV Database

BackgroundVancomycin can effectively inhibit Gram-positive cocci and is widely used in critically ill patients. This study utilized a large public database to explore the effect of patients' first vancomycin trough concentration (FVTC) on the occurrence of acute kidney injury (AKI) and mortality after receiving vancomycin treatment in intensive care unit (ICU).MethodsCritically ill patients who used vancomycin in the Medical Information Mart for Intensive Care (MIMIC) IV have been retrospectively studied. The outcomes included the occurrence of AKI during the use of vancomycin or within 72 h of withdrawal, ICU mortality and hospital mortality. Restricted cubic splines (RCS) were used to analyze the linear relationship between FVTC and the outcomes. Multivariate logistic/Cox regression analysis was used to analyze the association between patient's FVTC and the occurrence of AKI, ICU mortality, and in-hospital mortality.ResultsThe study ultimately included 3,917 patients from the MIMIC-IV database who had been treated with vancomycin for more than 48 h. First of all, the RCS proved the linear relationship between FVTC and the outcomes. After controlling for all covariates as confounders in logistic/Cox regression, FVTC was a risk factor with the occurrence of AKI (OR: 1.02; 95% CI: 1.01–1.04), ICU mortality (HR: 1.02; 95% CI: 1.01–1.03), and in-hospital mortality (HR: 1.02; 95% CI: 1.01–1.03). Moreover, patients were divided into four groups in the light of the FVTC value: group1 ≤ 10 mg/L, 10 <group 2 ≤ 15 mg/L, 15 <group 3 ≤ 20 mg/L, group4 > 20 mg/L. Categorical variables indicated that group 3 and group 4 had a significant relationship on the occurrence of AKI [group 3: (OR: 1.36; 95% CI: 1.02–1.81); group 4: (OR: 1.76; 95% CI: 1.32–2.35)] and ICU mortality [group 3: (HR: 1.47; 95% CI: 1.03–2.09); group 4: (HR: 1.87; 95% CI: 1.33–2.62)], compared to group 1, while group 4 had a significant effect on in-hospital mortality (HR: 1.48; 95% CI: 1.15–1.91).ConclusionsFVTC is associated with the occurrence of AKI and increased ICU and in-hospital mortality in critically ill patients. Therefore, in clinical practice, patients in intensive care settings receiving vancomycin should be closely monitored for FVTC to prevent drug-related nephrotoxicity and reduce patient mortality.

Impact of pharmacist intervention in reducing vancomycin-associated acute kidney injury: A systematic review and meta-analysis.

The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P< .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P< .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P< .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P= .0004). Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.

Comparison of single trough-based area under the concentration–time curve versus trough concentration for the incidence of vancomycin-associated nephrotoxicity

IntroductionWhile the revised 2020 consensus guideline recommends the use of area under the concentration–time curve (AUC)-guided vancomycin monitoring, collecting multiple vancomycin serum samples to calculate the AUC may cause clinical complications. The aim of the present retrospective study was to evaluate whether AUC-guided vancomycin monitoring, in which AUC was calculated based on a single trough concentration, is a better predictor of nephrotoxicity than trough-guided monitoring in patients receiving vancomycin therapy. MethodsA single-center, retrospective cohort study was conducted at the 614-bed Gifu University Hospital in Japan. Patients who received intravenous vancomycin for a documented or suspected infection and had their serum vancomycin trough concentration monitored between October 1, 2016 and September 30, 2020 were enrolled in the present study. ResultsMultivariate Cox proportional hazard analysis indicated that AUC (>600 μg•h/mL) was a significant risk factor for the incidence of acute kidney injury (AKI), while trough concentration (≥15 μg/mL) was not. Moreover, the AUC (>600 μg•h/mL) showed higher specificity and similar sensitivity to the trough concentration (≥15 μg/mL). Kaplan-Meier plots of the cumulative incidence of the AKI-free rate in patients indicated that the onset of AKI was significantly longer in patients with AUC ≤600 μg•h/mL than in patients with AUC >600 μg•h/mL (HR, 16.1; 95% CI, 6.3–41.2; p < 0.001). ConclusionAUC based on a single trough concentration was a better predictor of nephrotoxicity than trough concentration.

Mortality and Factors Related in Pediatric Intensive Care Unit Patients Treated with Vancomycin

Abstract There is limited information available regarding clinical outcome and rate of mortality in relation to invasive methicillin-resistant Staphylococcus aureus (MRSA) infection in pediatric intensive care unit (PICU) patients treated with vancomycin in this tertiary hospital in northern Thailand. Therapeutic drug monitoring (TDM) is recommended vancomycin prescription; however, it is important to investigate the outcome of this monitoring in PICU patients. This study aims to evaluate the mortality and factors related to these in PICU patients treated with vancomycin. A retrospective study was conducted in PICU patients given vancomycin from April 2018 to April 2019. The following variables were included: age, sex, underlying disease, diagnosis, length of stay (LOS) in PICU, Pediatric Index of Mortality 2 (PIM 2) score, mechanical ventilator use, renal replacement therapy (RRT), laboratory data, vancomycin dose, trough serum vancomycin concentration (Ctrough) and mortality rate. One hundred and sixty pediatric patients were enrolled into the study (median age 12 months, range 2-180 months, 69.4% male). Ctrough of vancomycin (10–20 mg/L) was recorded in 32.5% (n = 52) of cases. Septic shock was the most common diagnosis (49.3%) and the mortality rate was 39.4%. Results indicated that children who had a vancomycin Ctrough outside the therapeutic range, mechanical ventilator use and RRT use were statistically significantly associated with higher mortality rate (adjusted OR 3.29, 95% CI, 1.41-7.69; P &lt;0.05), (adjusted OR 6.22, 95% CI, 1.67-23.16; P &lt; 0.05) and (adjusted OR 10.41, 95% CI, 2.62-41.37; P &lt; 0.05). These factors were related to mortality and further studies are needed to determine if this outcome can be improved. Keywords: Vancomycin, Vancomycin trough concentration, Pediatric patients, Intensive care, Mortality, Factors related to mortality

Risk Scoring System for Vancomycin-Associated Acute Kidney Injury.

Vancomycin-associated acute kidney injury (AKI) remains a major challenge for patients and clinicians. This study aimed to construct a risk scoring system for vancomycin-associated AKI. We retrospectively reviewed medical records of patients who underwent therapeutic drug monitoring for vancomycin from June 2018 to July 2019. We selected possible risk factors for AKI by univariate and multivariable logistic regression analyses and developed a scoring system for vancomycin-associated AKI. Machine learning methods were utilized to predict risk factors for the occurrence of AKI. The incidence of vancomycin-associated AKI was 31.7% among 104 patients included in this study. A bodyweight ≤60 kg (two points), a Charlson comorbidity index ≥3 (two points), a vancomycin trough serum level >15 μg/ml (one point), and concomitant use of ≥6 nephrotoxic agents (two points) were included to construct a risk scoring system based on the coefficient from the logistic regression model. The area under the receiver operating characteristic curve (AUROC) (mean, 95% confidence interval (CI)) across 10 random iterations using five-fold cross-validated multivariate logistic regression, elastic net, random forest, support vector machine (SVM)-linear kernel, and SVM-radial kernel models was 0.735 (0.638–0.833), 0.737 (0.638–0.835), 0.721 (0.610–0.833), 0.739 (0.648–0.829), and 0.733 (0.640–0.826), respectively. For total scores of 0–1, 2–3, 4–5, 6–7, the risk of vancomycin-associated AKI was 5, 25, 45, and 65%, respectively. Our scoring system can be applied to clinical settings in which several nephrotoxic agents are used along with vancomycin therapy.

Augmented Renal Clearance of Vancomycin in Suspected Sepsis: Single-Center, Retrospective Pediatric Cohort.

To identify associations between augmented renal clearance (ARC) in pediatric patients treated for suspected sepsis and vancomycin pharmacokinetics. ARC has been associated with lower serum drug levels in both adult and pediatric cohorts for multiple drugs. We hypothesize that presence of ARC is associated with subtherapeutic initial vancomycin trough level (VTL). Retrospective study, with patients divided into two groups based on the presence of ARC (estimated glomerular filtration rate [eGFR] above 130 mL/min/1.73 m2) in comparison with VTL. Multivariable logistic regression analysis was performed to evaluate the association between eGFR and subtherapeutic VTL. Tertiary children's hospital. Hospitalized children (0-18 yr) initiated on empiric vancomycin therapy for suspected sepsis. Retrospective measurement of VTL, eGFR, and clinical variables. Seventy-three patients were treated with empiric vancomycin for sepsis. ARC was present in 32 patients (44%). Subtherapeutic first VTL was present in 40 patients (55%). Higher eGFR was independently associated with subtherapeutic VTL in the multivariable logistic regression analysis. Subtherapeutic VTL is associated with ARC in our single-center retrospective cohort of children with suspected sepsis. This problem may present a potential risk of treatment failure in Gram-positive sepsis or longer time to clinical response. Prospective studies to investigate the clinical significance and effect of optimizing vancomycin dose in patients with ARC are recommended.

Using Japanese big data to investigate novel factors and their high-risk combinations that affect vancomycin-induced nephrotoxicity.

Several factors related to vancomycin-induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high-risk combinations that influence VIN. We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5mg/dL or 1.5-fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method. Of the 7306 patients that were enrolled, VIN occurred in 14.2% of them (1035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio 0.701, 95% confidence interval 0.512-0.959), ward pharmacy service (0.741, 0.638-0.861), duration of VCM < 7days (0.748, 0.623-0.899) and trough concentrations 10-15 mg/L (0.668, 0.556-0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin-tazobactam use (2.056, 1.754-2.409) and piperacillin use (2.868, 1.298-6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin-tazobactam use was associated with the highest risk. We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin-tazobactam but also piperacillin may increase the risk.

P17 Vancomycin therapeutic drug monitoring—a call for change?

ObjectivesDespite the widespread use of vancomycin, optimization of dosing can be difficult. Increased vancomycin concentrations are associated with nephrotoxicity, while subtherapeutic levels may lead to inadequate antibacterial therapy and risk development of antimicrobial resistance. Recent guidelines have recommended the use of loading doses and switching to AUC24 TDM, targeting an AUC24:MIC ratio of 400–600 μg·h/mL to minimize toxicity while maintaining similar effectiveness for the treatment of serious infections. We aimed to review adherence to current local vancomycin dosing and conventional trough monitoring guidelines, as well as record time to, and factors related to, achieving target vancomycin troughs.MethodsFifty consecutive electronic prescriptions were screened for IV vancomycin use in treatment of active infections in a single acute Trust during April/May 2021. These were cross-referenced with microbiological, clinical and biochemical data from patient records. Variables were analysed by parametric or non-parametric methods on the basis of their normality distribution using GraphPad Prism.ResultsForty-one patients were included of which 39 had a vancomycin level measured. Mean age was 57 years (range 19–88) and BMI 28 (range 17–44). Nineteen had unstable renal function, including one receiving intermittent haemodialysis. Median CLCR was 95 mL/min (IQR 66–129). Indications were included on the prescription for 26. Median duration of vancomycin was 4 days (range 2–12), and half of patients ultimately switched therapy to an alternate agent . Target troughs were documented in 29 (70%), 9 of which had a target trough ≥15 μg/mL. Twenty-four had positive microbiology samples, 19 of which were organisms against which vancomycin would have expected activity. Five (13%) failed to achieve trough levels >10, 6/39 (15%) achieved troughs of 10–15, 13/39 (33%) 15–20, and 15/39 (38%) had troughs of >20 μg/mL (Figure 1). Where it was achieved, the median time to level ≥10 μg/mL was 46 h (range 11–202) and time to level ≥15 μg/mL was 68 h (range 18–243). Twenty-five (60%) patients required titration above the currently recommended initial dose, and 22 required doses of 1500 mg twice daily or higher. BMI did not correlate with vancomycin level achieved.Figure 1.Vancomycin trough ranges.ConclusionsA significant proportion of patients with serious infections fail to achieve or have a considerable delay in achieving therapeutic vancomycin trough. An even greater proportion have troughs above target and are at risk of nephrotoxicity. These findings support a potential switch to more personalized regimens using loading doses and AUC24 monitoring where vancomycin is the drug of choice. This would complement other stewardship measures to limit overall vancomycin use, achieve earlier and more complete source control, and optimize use of alternative antimicrobial therapies with more predictable PK/PD.

Body Mass Index of Elderly Patients with Normal Renal Function as a Determining Factor for Initial Vancomycin Regimen Designing

Introduction: Currently, the use of actual body weight is recommended for dosing in vancomycin regimen designs, and it is important to perform therapeutic drug monitoring for efficacy and safety. However, the method to determine the appropriate vancomycin regimen for underweight or obese patients remains controversial. The aim of this study was to evaluate the impact of body mass index (BMI) on the relationship among vancomycin doses, trough concentration, and area under the curve (AUC). In addition, we identified the group of patients who were potentially more affected by BMI and evaluated the optimal dosing regimen to achieve the target AUC. Methods: We retrospectively collected data from 462 patients who received vancomycin at the Osaka City University Hospital between January 2013 and September 2019. Patients were classified by their BMI group (underweight <18.5, normal weight 18.5–24.9, and obese ≥25.0 kg/m2). We assessed the association between vancomycin dose versus trough concentration or AUC as well as dose-adjusted trough concentration and AUC in each BMI subgroup to determine the doses for achieving the target AUC. Results: The dose-adjusted trough concentration and AUC in elderly patients with normal renal function appeared to increase significantly with an increase in BMI (p < 0.05). Vancomycin doses that enabled the achievement of AUC400 in elderly patients with normal renal function decreased with increasing BMI: 17.7, 15.8, and 12.9 mg/kg per time in the underweight, normal weight, and obesity groups, respectively (p < 0.05). Conclusion: Elderly patients with normal renal function were the most affected by BMI on vancomycin trough concentration and AUC. The vancomycin regimen design in these patients should be adjusted carefully, not only based on the patient’s renal function but also based on BMI.

Determinants of Vancomycin Trough Concentration in Patients Receiving Continuous Veno-Venous Hemodialysis.

Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

AI Models to Assist Vancomycin Dosage Titration.

Background: Effective treatment using antibiotic vancomycin requires close monitoring of serum drug levels due to its narrow therapeutic index. In the current practice, physicians use various dosing algorithms for dosage titration, but these algorithms reported low success in achieving therapeutic targets. We explored using artificial intelligent to assist vancomycin dosage titration. Methods: We used a novel method to generate the label for each record and only included records with appropriate label data to generate a clean cohort with 2,282 patients and 7,912 injection records. Among them, 64% of patients were used to train two machine learning models, one for initial dose recommendation and another for subsequent dose recommendation. The model performance was evaluated using two metrics: PAR, a pharmacology meaningful metric defined by us, and Mean Absolute Error (MAE), a commonly used regression metric. Results: In our 3-year data, only a small portion (34.1%) of current injection doses could reach the desired vancomycin trough level (14–20 mcg/ml). Both PAR and MAE of our machine learning models were better than the classical pharmacokinetic models. Our model also showed better performance than the other previously developed machine learning models in our test data. Conclusion: We developed machine learning models to recommend vancomycin dosage. Our results show that the new AI-assisted dosage titration approach has the potential to improve the traditional approaches. This is especially useful to guide decision making for inexperienced doctors in making consistent and safe dosing recommendations for high-risk medications like vancomycin.

The Thirty-Day Mortality Rate and Nephrotoxicity Associated With Trough Serum Vancomycin Concentrations During Treatment of Enterococcal Infections: A Propensity Score Matching Analysis.

The objective of this study was to evaluate the relationship between vancomycin trough levels in patients with documented enterococcal infections and mortality, clinical outcomes, microbiological outcomes, and nephrotoxicity. We conducted a retrospective cohort study of patients with enterococcus infections who were prescribed vancomycin with therapeutic drug monitoring during January 2010 and December 2019 at Chiang Mai University Hospital (CMUH). The study enrolled 300 participants who met the inclusion criteria and were prescribed vancomycin with therapeutic drug monitoring. The results of this study showed that, after propensity score matching, a vancomycin trough of ≥15 mg/L was associated with significant differences in 30-days mortality compared to a vancomycin trough of <15 mg/L (aHR: 0.41, 95% CI: 0.21–0.82; p = 0.011). Likewise, a vancomycin trough of ≥15 mg/L was associated with significant differences in the clinical response (aHR: 0.49, 95% CI: 0.26–0.94; p = 0.032), microbiological response (aHR: 0.32, 95% CI: 0.12–0.87; p = 0.025) and nephrotoxicity (aHR: 3.17, 95% CI: 1.39–7.23; p = 0.006), compared with a vancomycin trough of <15 mg/L. However, sub-group analysis found that very high trough levels (>20 mg/L) were also associated with a high rate of nephrotoxicity (aHR: 3.55, 95% CI 1.57–8.07, p = 0.002), when compared with a vancomycin trough of <15 mg/L. The target vancomycin trough concentration was ≥15 mg/L and this target can be an optimal alternative to the use of area under the curve (AUC) values for monitoring the treatment of enterococcal infection.

The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin

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.

Vancomycin area under the curve/minimum inhibitory concentration and trough level concordance-evaluation on an urban health unit.

A vancomycin AUC/MIC (area under the curve/minimum inhibitory concentration) of 400-600 mg•h/L is associated with improved clinical outcomes for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. Currently, there are still limited studies evaluating the relationship between vancomycin trough and AUC. To evaluate the correlation between vancomycin trough and AUC/MIC and determine if trough-guided monitoring is an adequate predictor of AUC/MIC in the Urban Health population at St Paul's Hospital. This was a retrospective chart review of 29 patients from November 2019 to February 2021. Patient demographics and laboratory data were collected from electronic medical records. The two-level equation-based approach was used to calculate AUC/MIC. The proportion of AUC/MIC values within target (400-600 mg•h/L) despite subtherapeutic troughs, and the proportion of AUC/MIC values supratherapeutic when trough is within target (15-20 mg/L) were the primary endpoints. Fifty-seven sets of levels were collected and 75% of vancomycin troughs and AUC24 were found to be discordant. When trough was 10-14.9 mg/L, AUC24 was > 400 mg•h/L in 94% of cases and when trough was 15-20 mg/L, AUC24 was > 600 mg•h/L in 69% of cases. There was a moderate correlation between vancomycin trough and AUC24h (R 2 = 0.57; p < 0.001). A vancomycin trough between 15 and 20 mg/L may result in an AUC/MIC greater than necessary for clinical efficacy. Considering these findings and the practical concerns of AUC-guided monitoring, a modest reduction in target troughs to prevent vancomycin toxicity warrants clinical consideration and further evaluation.

Comparing two equations for estimation of kidney function (Cockcroft-Gault and Glomerular Filtration Rate Assessment in Liver Disease) for vancomycin dosing in adult liver transplant recipients: a pilot, randomized clinical trial

Background: In the setting of impaired liver function, estimation of glomerular filtration rate (GFR) using common creatinine-based equations is inaccurate. Recently, the Glomerular filtration Rate Assessment In Liver disease (GRAIL) model has been introduced to estimate GFR in liver transplantation. This study was conducted to compare vancomycin dose adjustment in liver transplant patients using Cockcroft-Gault (C-G) versus the GRAIL method. Methods: In this pilot, randomized clinical trial, adult liver transplant recipients who were a candidate to receive intravenous vancomycin were enrolled. The level of kidney function was estimated using the GRAIL model and C-G equation in the intervention and control arms, respectively. Then, vancomycin maintenance doses were accordingly adjusted. At the steady state, peak and trough serum concentrations of vancomycin were collected for area under the concentration-time curve (AUC) calculation and pharmacokinetic comparisons. Results: Fifteen patients were enrolled in each arm of study. The mean daily dose of vancomycin was estimated insignificantly lower for individuals in the GRAIL arm than the C-G group (1550.00±544.45 versus 1750.00± 389.60mg). Compared with the C-G group, a higher rate of patients in the GRAIL arm experienced below-target vancomycin trough concentrations (40.0% versus 13.3%), and a lower rate showed above target trough concentration (40.0% versus 66.7%). These differences did not reach statistical significance. Individuals in the GRAIL arm represented significantly higher rate of below target vancomycin AUC/MIC than patients in the C-G arm (46.7% versus 6.7%) (P=0.049). No differences in clinical outcomes were observed between the two groups. Conclusion: Using the GRAIL model for vancomycin dosing may result in less percent of patients with at target AUC/MIC compared to the C-G method and expose more patients at risk for vancomycin under dosing.

1097. A Comparison of Area-Under Curve (AUC)-Guided vs Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-analysis

BackgroundTrough levels have been used for Vancomycin (VAN) therapeutic drug monitoring (TDM) historically due to its practicality. A paradigm shift towards the use of area under curve (AUC)-guided dosing TDM has been made due to availability of advanced pharmacokinetics software, variability between trough levels and AUC values and the potential for reducing toxicity. This review aims to evaluate the impact of AUC-guided vs trough-guided vancomycin TDM on nephrotoxicity-related outcomes.MethodsA systematic review was conducted using PubMed®, Embase®, Web of Science®, CINAHL®, Google scholar and Cochrane library® up till 1st January 2021 and was reported according to the PRISMA checklist. Studies which evaluated AUC-guided or trough-guided VAN TDM and vancomycin-associated nephrotoxicity were included. Random effects models were used to compare differences in nephrotoxicity between trough level or AUC based vancomycin TDM due to expected heterogeneity in study designs. PRISMA Flowchart PRISMA flow chart depicting the selection process of studies included in the meta-analysisResultsOf 1191 records retrieved, 57 studies were included. Majority of studies included adult and elderly patients (n=47, 82.5%). The pooled prevalence of nephrotoxicity was lower using the AUC-guided TDM [6.2%, 95% confidence interval (CI): 2.9 – 9.5%] compared to trough-guided TDM [17.0%; 95% CI: 14.7 – 19.2%]. The risk of nephrotoxicity was lower with the AUC-guided approach as compared with the trough-guided approach [OR: 0.53, 95% CI: 0.32–0.89]. AUC thresholds correlated with risk of nephrotoxicity only for the first 96 hours of therapy. A frequency analysis of significant multivariable factors showed that concomitant use of nephrotoxins, VAN trough levels and duration of VAN therapy were most commonly associated with nephrotoxicity.Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guidedPooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from AUC-guided monitoringPooled nephrotoxicity rates from trough-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoringConclusionThe AUC-guided approach appeared to have lower risk of nephrotoxicity which supports the updated American Society of Health-System Pharmacists recommendations. More studies should be performed to evaluate the optimal derivation of AUC and clinical utility of repeated measurements of vancomycin AUC and trough levels.Disclosures All Authors: No reported disclosures

1085. Comparison of the Incidence of AKI in Vancomycin AUC Based Goal Trough Dosing vs. Traditional Trough Dosing in the Outpatient Setting

Abstract Background Recent changes to vancomycin guidelines recommend dosing by targeting an AUC of 400-600 in most patients, due to similar effectiveness and reduced rates of acute kidney injury (AKI). AKI was defined as an increase in serum creatinine of ≥ 0.5 mg/dl, a 50% increase in serum creatinine from baseline on two consecutive readings, or a decrease in creatinine clearance from 50% from baseline on two consecutive readings. The purpose of this study was to assess the incidence of AKI in patients receiving vancomycin dosed by AUC based trough goals and vancomycin dosed by traditional trough goals (15-20 mcg/mL) in the outpatient setting. Methods This study was performed by retrospective chart review using the electronic health record. Patients receiving vancomycin outpatient as continuation of therapy after discharge from December 1, 2018 through March 24, 2021 were reviewed. The primary objective was incidence of AKI in patients receiving vancomycin outpatient with trough goals derived from patient specific AUC calculations compared to patients receiving vancomycin by traditional goal troughs. Secondary objectives included rate of treatment failure, average AUC estimated trough range, and number of regimen changes required. Results There were a total of 65 patients in the traditional trough dosing group and 53 patients in the AUC trough dosing group. The incidence of AKI was higher in the traditional trough dosing group compared to the AUC trough group (23.1% vs 5.7%; p=0.01). There were no differences in incidence of treatment failure. The mean AUC estimated trough range was 11.4-16.9 mcg/mL. There were significantly less average regimen changes required in the AUC dosing group (1.64 vs 1.13; p=0.006). Patients receiving AUC trough dosing were 78% less likely to develop AKI as patients receiving traditional trough dosing (HR 0.221, 95%CI 0.051 – 0.968). Conclusion There was a significantly lower incidence of AKI in patients receiving vancomycin dosed by AUC based troughs compared to traditional trough dosing. Continuing AUC trough based dosing for vancomycin in the outpatient setting is convenient and may lead to reduced rates of AKI. Disclosures Dustin R. Carr, PharmD, BCPS, BCIDP, AAHIVP, Merck (Speaker’s Bureau)