Therapeutic Monitoring of Vancomycin for MRSA Guidelines, 2020

Rybak et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy, 19 March 2020, zxaa036

IDSA MRSA Guidelines, 2011

Liu et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections in Adults and Children. Clinical Infectious Diseases, Volume 52, Issue 3, 1 February 2011, Pages e18–e55

Vancomycin Therapeutic Monitoring for MRSA Canadian Guidelines, 2020

Cuello et al. Vancomycin therapeutic monitoring for serious methicillin-resistant Staphylococcus aureus infections. Ottawa: CADTH; September 2020



NEW! Johnston et al. Optimizing outcomes using vancomycin therapeutic drug monitoring in patients with MRSA bacteremia: trough concentrations or area under the curve?

In 89 patients with MRSA bacteremia, initial vancomycin troughs < 10.6 mg/L, AUC < 410 mg*hr/L, and ICU admission were associated with treatment failure in multivariate analyses. Supratherapeutic AUC levels (> 600 mg*hr/L), but not supratherapeutic troughs (> 20 mg/L), were associated with nephrotoxicity.

NEW! Katip et al. A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections

Retrospective cohort study of 312 patients with Enterococcal infections found that vancomycin AUC ≥ 400 mg*hr/L was associated with significantly improved clinical & microbiological response compared to AUC < 400 mg*hr/L (aHR 0.50; 95% CI 0.26-0.97, P=0.042 & aHR: 3.96; 95% CI 1.09–14.47, P=0.037, respectively). Regarding safety, higher AUC (≥ 400 mg*hr/L) was associated with significantly greater rates of nephrotoxicity compared to lower targets of AUC < 400 mg*hr/L (aHR: 3.96; 95% CI 1.09-14.47; p=0.037).

Alosaimy et al. Vancomycin area under the curve to predict timely clinical response in the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft tissue infections

Among 154 patients with complicated MRSA skin and soft tissue infections (SSTI) classification and regression tree (CART) analysis identified an AUC > 435 mg*hr/L for timely clinical success. Attainment of this AUC was associated with improved clinical outcomes in a retrospective, single center, cohort study.

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

Among 252 adult patients receiving vancomycin comparing trough versus AUC estimates for target therapeutic ranges, only 19% of trough concentrations versus 70% of AUCs were therapeutic. Use of Bayesian AUC-guided dosing was associated with fewer blood samples, shorter therapy durations, and reduced nephrotoxicity.

Hale et al. Are Vancomycin Trough Concentrations of 15 to 20 mg/L Associated With Increased Attainment of an AUC/MIC ≥ 400 in Patients With Presumed MRSA Infection?

Among 100 patients with confirmed MRSA infections, failure of target attainment of a trough > 10 mg/L were 73% less likely to achieve an AUC/MIC > 400 mg*hr/L , however no difference was found related to AUC/MIC target attainment in patients with troughs of 10-14.9 mg/L, 15-20 mg/L, or > 20 mg/L. Higher rates of nephrotoxicity were found in patients with trough levels > 10 mg/L.

Mogle et al. Implementation of a two-point pharmacokinetic AUC-based vancomycin therapeutic drug monitoring approach in patients with methicillin-resistant Staphylococcus aureus bacteraemia

A retrospective, single center cohort study of 46 patients receiving vancomycin for MRSA bacteremia demonstrated overall clinical success and nephrotoxicity rates of 81.8% and 13.0%, respectively. CART-derived vancomycin AUC thresholds for clinical success and nephrotoxicity were >297 mg*hr/L and >710 mg*hr/L , respectively, indicating that vancomycin AUC targets should aim for values of 400-600 mg*hr/L when using two-point kinetics.



NEW! Hashimoto et al. Candidates for area under the concentration–time curve (AUC)-guided dosing and risk reduction based on analyses of risk factors associated with nephrotoxicity in vancomycin-treated patients

Retrospective cohort study across 7 hospital centers in Japan from 2008-2019 including 1882 patients with suspected MRSA infection, who received vancomycin, and had trough levels monitored. 8.4% of patients developed AKI, 6% (10/159) on Day 1, 77% (123/159) within 7 days, and 23% (36/159) from 8-14 days from start of treatment. CART-derived AKI onset day was 7.3 days. CART-derived cut-off Cmin associated with AKI within 7 days was 19.3 mg/L. Cmin >20 mg/L was associated with stronger risk for early (<7d) and late (8-14) AKI compared with Cmin >15 mg/L. Loading dose of >15 mg/kg was not associated with AKI while pip-tazo use, diuretic use, ICU stay, and pre-existing renal dysfunction (eGFR<30) were associated with higher AKI risk. In patients who require a lower target Cmin range, AUC-guided dosing based on two pharmacokinetic samples should be considered to continue treatment in order to prevent vancomycin-induced AKI and to confirm achievement of the AUC.

NEW! Liu et al. Vancomycin Exposure and Acute Kidney Injury Outcome: A Snapshot From the CAMERA2 Study

Sub-analysis of CAMERA2 study which demonstrated that among 291 patients, day 2 vancomycin exposure was significantly associated with nephrotoxicity, with AUC24-48h cut-points found at 470.1 (OR, 2.7; 95% CI, 1.5–5.0), 496.1 (OR, 5.29; 95% CI, 2.2–12.7), and 525.5 (OR, 6.8; 95% CI, 2.2–21.1) mg*hr/L for m-KDIGO stages ≥1, ≥2, and 3, respectively.

NEW! Poston-Blahnik et al. Association Between Vancomycin Area Under the Curve and Nephrotoxicity: a single center, retrospective cohort study in a veteran population

Among 200 select patients at the St. Louis VA Healthcare System receiving vancomycin for at least 4 days, rates of AKI were compared. Older patients (≥ 70 years), low baseline creatinine clearance (< 50 mL/min), and vancomycin AUC > 550 were independently associated with AKI.

Aljefri et al. Vancomycin Area Under the Curve and Acute Kidney Injury: A Meta-analysis

A systematic review and meta-analysis of eight observational studies of 2491 patients demonstrated that AUC less than 650 mg*hr/L was associated with decreased AKI in the first 48 hours and AUC monitoring strategies were associated with reduced AKI rates compared to trough-guided monitoring.

Barreto et al. Navigating the Muddy Waters of Vancomycin Nephrotoxicity

Nephrotoxicity associated with vancomycin necessitates more accurate and precise vancomycin dosing models, particularly in high-risk subpopulations including obese patients, critically-ill, and those with reduced glomerular filtration rates.

Chavada et al. Establishment of an AUC0-24 Threshold for Nephrotoxicity Is a Step towards Individualized Vancomycin Dosing for Methicillin-Resistant Staphylococcus aureus Bacteremia

Among 127 consecutive patients with MRSA bacteremia who received vancomycin monotherapy for at least 14 days, AKI was observed in 15.7% of patients. Higher trough concentrations (17.2 mg/L v 13.1 mg/L) were associated with AKI, with classification and regression tree analysis identifying a vancomycin AUC threshold for AKI of >563 mg*hr/L .

Lodise et al. The Emperor’s New Clothes: PRospective Observational Evaluation of the Association Between Initial VancomycIn Exposure and Failure Rates Among ADult HospitalizEd Patients With Methicillin-resistant Staphylococcus aureus Bloodstream Infections (PROVIDE)

A prospective multicenter observational study of 265 hospitalized patients with MRSA bacteremia who received vancomycin were found to have treatment failure (death within 30 days or persistent bacteremia >7 days) at a rate of 18% and AKI at a rate of 26%, and patients with day 2 AUC < 515 mg*hr/L experienced the best global outcomes (no treatment failure nor AKI).

Finch et al. A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity

Among 1280 patients at Detroit Medical Center, AUC-guided dosing was independently associated with lower nephrotoxicity (OR 0.52) compared to traditional trough-based dosing, with reduced nephrotoxicity associated with reduced vancomycin exposure.

Lodise TP, Drusano G. Vancomycin Area Under the Curve–Guided Dosing and Monitoring for Adult and Pediatric Patients With Suspected or Documented Serious Methicillin-Resistant Staphylococcus aureus Infections: Putting the Safety of Our Patients First

Despite a lack of double-blind, randomized, controlled trials, best-available evidence indicates that vancomycin is nephrotoxic with risk of AKI driven by increasing daily AUC. Trough measurements are more imprecise and unable to ensure safety nor efficacy. Transitioning to AUC-guided dosing for vancomycin may be a challenge, but it is necessary to maintain safety for patients, otherwise use of alternative agents for severe MRSA infections should be considered.

Tsutsuura, M., Moriyama, H., Kojima, N. et al. The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing

A systematic review and meta-analysis demonstrated that increased (>20 μg/ml) vancomycin trough concentrations were associated with higher incidence of acute kidney injury compared to ranges of 15-20 μg/ml (OR 2.39, 95% CI 1.78-3.20). AUC/MIC of 400-600 resulted in lower treatment failure rates (OR 0.28, 95% CI 0.18-0.45), while AUC/MIC greater than 600 significantly increased the risk of AKI (2.10, 95% CI 1.13-3.89). Incidence of AKI was lower in patients receiving vancomycin via AUC-guided monitoring compared to trough-guided monitoring.

Post-Blahnik A, Moenster R. Association between vancomycin area under the curve (AUC) and nephrotoxicity

A retrospective cohort of 200 patients demonstrated that patients with vancomycin AUC > 550 were associated with higher peak serum creatinine (1.48 mg/dl v 1.22 mg/dl, p=0.015) and higher rates of AKI (42% v 2%, P<0.05) compared to those with AUC < 550. Age > 70 years, CrCl < 50ml/min, and AUC > 550 were found to be associated with AKI risk.

Avedissian AN et al. The pharmacodynamics-toxicodynamic relationship and Cmax in vancomycin-induced kidney injury in an animal model

Animal studies and PK analyses demonstrated kidney injury marker-1 (KIM-1) values were increased in more infrequent vancomycin dosing strategies (i.e. 300-400mg/kg/day divided in once or twice daily dosing compared to three or four times daily dosing). Exposure-response relationships were seen for KIM-1 and Cmax0-24, with Cmax0-24 being the most predictive PK-TD contributor of vancomycin-induced AKI.


Special Populations

NEW! Bosley et al. Optimization of Vancomycin Dosing to Achieve Target Area Under the Curve in Pediatrics

Retrospective study of 77 pediatric patients (ages 1 month to 18 years) which found that vancomycin dose requirements differed to achieve target AUC/MIC ranges, with higher dose requirements among younger patients. Mean dose requirements corresponding with AUC (400-600 mg*hr/L) were 79 ± 14.1 mg/kg/day for ages 1 month to 5 years, 65.6 ± 21.1 mg/kg/day for ages 6 to 12 years, and 53.9 ± 17.1 mg/kg/day for ages 13 to 18 years (p<0.001).

NEW! D’Amico et al. Acute kidney injury associated with area under the curve versus trough monitoring of vancomycin in obese patients

Retrospective study of 1024 obese (BMI ≥30 kg/m2) patients who received > 72 hours of vancomycin with corresponding concentrations comparing trough-based to AUC-based dosing. Significantly lower rates of AKI were found in the AUC-guided group compared to trough-based monitoring (22.7% v 16.3%, p=0.008).

NEW! Han et al. Implementation of Vancomycin Therapeutic Monitoring Guidelines: Focus on Bayesian Estimation Tools in Neonatal and Pediatric Patients

This paper compares several published neonatal and pediatric population PK models and commercially available Bayesian dosing software to assist in implementation of AUC-based dosing in the neonatal and pediatric populations. Bayesian-guided AUC-based dosing and monitoring is possible in the pediatric and neonatal populations with multiple pop PK models and dosing tools available to best fit an institution’s patient population.

NEW! He at al. Population Pharmacokinetics and Dosing Optimization of Vancomycin in Infants, Children, and Adolescents with Augmented Renal Clearance

In this pharmacokinetic modeling study, vancomycin dosing for pediatric patients with augmented renal clearance (eGFR > 160) was examined. Guideline suggested dosing strategies of 60mg/kg/day yielded 24h AUC lower than the goal set by the authors of 400 – 700 mg*hr/L. The authors propose doses of 70mg/kg/day and 75 mg/kg/day for patients aged 0 – 12 and 13 – 18, respectively.

NEW! Hodiamont et al. Impact of a vancomycin loading dose on the achievement of target vancomycin exposure in the first 24 h and on the accompanying risk of nephrotoxicity in critically ill patients

Prospective, observational, before/after study of 82 critically ill patients receiving vancomycin, which found among 104 vancomycin courses, loading doses of 25 mg/kg led to significantly more patients achieving an AUC of at least 400mg*hr/L. No increased risk of acute kidney injury (AKI) was observed, however, higher exposure was associated with AKI.

NEW! Lewis et al. Evaluation and Development of Vancomycin Dosing Schemes to Meet New AUC/MIC Targets in Intermittent Hemodialysis Using Monte Carlo Simulation Techniques

In silico study using Monte Carlo simulations of AUC targets (AUC ≥ 400 mg*hr/L for MRSA MIC of 1 mg/L) for one week of thrice-weekly vancomycin dosing found that traditional dosing is unlikely to meet AUC targets. Loading doses of 25-35 mg/kg followed by maintenance doses of 7.5-15 mg/kg are necessary in 90% of simulated patients. Using a single vancomycin serum concentration targeting 20 mg/L prior to the second dialysis session enhances the target attainment probability.

Crass et al. Dosing vancomycin in the super obese: less is more

Among 346 obese and super obese patients with BMI ranging from 30.1-85.7 kg/m2, Monte Carlo simulation demonstrated that maintenance vancomycin doses > 4500 mg/day were not required to achieve pharmacodynamics AUC targets. A population modeling using linear combinations of age, SCr, sex, and total body weight (scaled allometrically to an exponent of 0.75) was more predictive of clearance.

Pongchaidecha et al. Vancomycin Area under the Curve and Pharmacokinetic Parameters during the First 24 Hours of Treatment in Critically Ill Patients using Bayesian Forecasting

Retrospective study of 66 critically ill patients to determine the AUC and pharmacokinetic parameters on the first day of vancomycin administration using Bayesian models within PrecisePK software. The clearance (Cl) of vancomycin correlated with creatinine clearance, and volume of distribution (Vd) significantly correlated with age and body weight. Among critically ill patients, Vd and Cl values were higher and larger vancomycin loading doses (25-30 mg/kg) may be necessary to achieve target AUC within the first 24 hours of therapy.

Jung et al. Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Adults on Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

Development and evaluation of a population pharmacokinetic model for vancomycin in adult patients on extracorporeal membrane oxygenation (ECMO). This study demonstrated that it is difficult to achieve efficacy and safety AUC/MIC (400-600) targets in patients on ECMO when using population dosing and Monte Carlo simulations.

Yoo R et al. Impact of initial vancomycin pharmacokinetic/pharmacodynamic parameters on the clinical and microbiological outcomes of methicillin-resistant Staphylococcus aureus bacteremia in children

A retrospective observational study of 73 pediatric patients (aged 2 months to 18 years) with MRSA bacteremia demonstrated a weak linear relationship between Ctrough and the corresponding AUC/MIC (r=0.234). Initial AUC/MIC < 300 may be a predictor for persistent MRSA bacteremia beyond 48 hours, however this should be validated in prospective trials.



NEW! Huang et al. Doing More With Less: Pragmatic Implementation of Vancomycin Area-Under-the-Curve (AUC) Monitoring

Four cycles of a step-by-step quality improvement process were performed in 35 patients to evaluate feasibility and barriers associated with AUC-guided monitoring. The authors determined a hybrid approach was pragmatic and cost effective, with trough-based monitoring favored in patients on short-course vancomycin and AUC-guided monitoring for patients with higher risk of nephrotoxicity.

NEW! Katawethiwong et al. Effectiveness of a vancomycin dosing protocol guided by area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) with multidisciplinary team support to improve hospital-wide adherence to a vancomycin dosing protocol: A pilot study

Addition of multidisciplinary team adherence and vancomycin monitoring to an existing AUC-based dosing and monitoring protocol improved adherence to the protocol (aOR 10.31, 95% CI 4.54-23.45), decreased the 30-day mortality rate (8.3% vs 20%, p=0.015), and has numerically reduced nephrotoxicity (5% vs 10.8%, p=0.15).

Heil et al. Making the change to area under the curve-based vancomycin dosing

Improved safety, including reduced rates of AKI, can be achieved by implementing AUC-based vancomycin dosing led by pharmacists in conjunction with support and education from hospital partners.

Claeys et al. Pharmacists’ perceptions of implementing a pharmacist-managed area under the concentration time curve-guided vancomycin dosing program at a large academic medical center

A survey of 127 pharmacists who completed vancomycin dosing training before and after transitioning to AUC-guided pharmacist dosing program at UMMC found that AUC-based dosing was supported to a greater degree than trough-based dosing. AUC-based dosing took slightly longer to perform (15 min v 8 min), was associated with a sense of practicing at the highest degree of one’s licensure, and computer decision support is key to a successful rollout.

Gregory et al. Vancomycin Area Under the Curve Dosing and Monitoring at an Academic Medical Center: Transition Strategies and Lessons Learned

Three stages including preparation, implementation, and evaluation were used to establish an AUC-based vancomycin dosing strategy. This strategy required education to key stakeholders, training of pharmacy staff, development of monitoring guideline documents, institution-wide education, technology development and support, and quality improvement research.

Meng et al. Conversion from Vancomycin Trough Concentration-Guided Dosing to Area Under the Curve-Guided Dosing Using Two Sample Measurements in Adults

Among 296 patients who received vancomycin before and after an AUC-based dosing strategy (using two-point kinetics) was implemented at Stanford Health, AUC-based dosing was associated with improved therapeutic target attainment (400-800 mg*hr/L) compared to trough-based strategies with lower rates of nephrotoxicity, albeit non-significant.

Bradley et al. Assessment of the implementation of AUC dosing and monitoring practices with vancomycin at hospitals across the United States

A survey study of 200 pharmacists demonstrated that most respondents have yet to implement AUC dosing (70.3%) but plan to do so in the next year (57%). Intended methods of AUC dosing varied between purchased Bayesian software (38%) and homemade software (35%), with user friendliness identified as a highly-valued factor.

Bland et al. Transitioning from guidelines approval to practical implementation of AUC-based monitoring of vancomycin

A survey study of 309 ACCP members demonstrated an array of vancomycin dosing strategies including: non-pharmacists clinicians dosed vancomycin in majority of patients (19%), institutions planned to continue using trough-based monitoring strategies (18%), and hospitals employing an infectious diseases pharmacist were more likely to report recent/pending transition to AUC-based dosing.

Rybak et al. Validity of 2020 vancomycin consensus recommendations and further guidance for practical application

Based on available evidence, vancomycin is nephrotoxic and drives AKI, with trough monitoring being an imprecise measurement of AUC. AUC is a preferred method to reduce risk of AKI while optimizing efficacy, and should be done to prioritize the safety of patients despite the implementation barriers.

Gregory et al. Vancomycin area under the curve dosing and monitoring at an academic medical center: Transition strategies and lessons learned

Successful implementation of vancomycin AUC monitoring requires an organized process and inclusion of key stakeholders to ensure all users are educated once technology has been developed. Throughout the implementation process, continued support for end-users should be available. Additionally, evaluation and dissemination of AUC-based dosing results should occur.

Lee et al. Cost-benefit analysis comparing tough, two-level AUC and Bayesian AUC dosing for vancomycin

A cost-benefit analysis demonstrated two-sample AUC versus trough dosing saved an average of $846 per patient encounter and a single-sample Bayesian AUC versus trough dosing saved $2065 per patient encounter. Based on these findings, only 41 patients would have to be dosed and monitored using a Bayesian software program (costing up to $100,000) in order to be cost-effective.



Diekema et al. Twenty-Year Trends in Antimicrobial Susceptibilities Among From the SENTRY Antimicrobial Surveillance Program

The SENTRY Antimicrobial Surveillance Program evaluated in vitro activity of 191,460 S. aureus isolates, of which 40.3% were MRSA. Forty-seven percent of those isolates originated from North America, indicating occurrence rates of 33.1% (1997-2000), 44.2% (2005-2008), 42.3% (2009-2012), and 39.0% (2013-2016), with no demonstrated increase of MIC > 1 mg/L in any of the isolates.


Bayesian and Pharmacokinetic Models

NEW! Fewel et al. Vancomycin area under the curves estimated with pharmacokinetic equations using trough-only data

Study to examine AUCs through estimation from trough-only data compared with peak and trough concentrations. Data gathered from parameters entered into with 4,343 entries. Root mean square error (RMSE), bias (diff between AUCref and mean estimated AUCs), and correlation were generated and a derived Vd equation of Vd (L) = 0.29(age) +0.33(total BW in kg) +11 was made from trough-only VancoPK data that correlated 0.926 with actual AUC, and >95% of estimated AUCs were within 100 points of actual AUCs.

NEW! Ho et al. Bayesian-estimated vancomycin area under the curve using a single trough concentration vs 2 concentrations

Sixty-five vancomycin regimens for 63 unique patients with at least 2 collected vancomycin concentrations were compared to evaluate AUC over 24 hours using 1 vs. 2 vancomycin concentrations. The relationship between AUC obtained from 1 vs. 2 concentrations was significant (χ2 [1, n = 65] = 36.2, P < 0.001), with an estimated 58/65 dosing regimens requiring no change based on 1 concentration alone.

NEW! Hsu Mang et al. Comparison of area under the curve for vancomycin from one- and two-compartment models using sparse data

Simulated vancomycin concentration points (15 min intervals among 100 pts) were used to calculate a reference AUC and compare this AUCref to data-depleted datasets (trough-only and peak-trough datasets). One and two-compartment models were also built from the depleted set and compared. AUCs from the two-compartment model with trough-only data did not adequately represent the true AUCref, with significant differences of 25.16% for AUC0–24, 15.92% for AUC24–48 and 19.45% for AUCavg. The level of difference between AUCs of one and two compartment models were <17% in peak-trough data models.

NEW! Scheetz et al. Of Rats and Men: a Translational Model To Understand Vancomycin Pharmacokinetic/Toxicodynamic Relationships

Modelling of animal (rat) and human studies (PROVIDE & CAMERA2) demonstrated that the rate of AKI, determined by KIM-1 and histopathology scores in rats and SCr in humans, increased as a function of the daily log10 AUC, with the rat model being more sensitive in detecting AKI across therapeutic AUCs in clinical studies. This demonstrates that animal studies provide useful translational information related to risk of vancomycin toxicity in human subjects.

Turner et al. Review and Validation of Bayesian Dose-Optimizing Software and Equations for Calculation of the Vancomycin Area Under the Curve in Critically Ill Patients

Five Bayesian dose-optimizing software programs including Adult and Pediatric Kinetics, BestDose, DoseMe, InsightRx, and Precise PK, along with two first-order pharmacokinetic equations were evaluated among a dataset of 19 critically ill patients for validation of the AUC estimate. The study found that InsightRx was the most adaptable, easiest to use, and featured the most company support. Precise PK and BestDose had the most accurate estimates despite increased difficulty in use and the accuracy values of BestDose exhibited the most variability. By using two levels, pharmacokinetic equations produced similar or better accuracy and bias as compared with Bayesian software.

Carreno et al. Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling

The Albany Medical Center performed Bayesian PK (ADAPT V) sampling of 12 obese patients receiving vancomycin for suspected or confirmed Gram-positive infections with 5 PK concentrations for each patient using four different PK models as Bayesian priors. The authors found that AUC using two-level peak and trough provided the best approximation for the vancomycin AUC.

Cunio et al. Towards precision dosing of vancomycin in critically ill patients: an evaluation of the predictive performance of pharmacometric models in ICU patients

Retrospective data from 82 adult ICU patients who received vancomycin were used to predict serum concentrations a priori or with Bayesian forecasting among 12 vancomycin models, with the Goti model being the only clinically acceptable model for both a priori and Bayesian forecasting. The Llopis and Roberts model were also clinically appropriate using Bayesian forecasting.

Broeker et al. Towards precision dosing of vancomycin: a systematic evaluation of pharmacometric models for Bayesian forecasting

A systematic evaluation of 31 population models for vancomycin in NONMEM®7.4 using data from 292 hospitalized patients to predict forecasting bias, precision, and visual predictive checks found that a priori predication varied substantially and was best for models that included body weight and creatinine clearance as covariates, with the Goti model providing the best predictive performance, most accurate visual predictive checks, and AUC predictions.

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

Demonstrates the value of continuous learning for model-informed precision dosing to prevent error or bias in dose selection due to use of models that were developed in alternative patient populations. This study describes that current pediatric pharmacokinetic models in literature could be improved to reduce prediction error by up to 13% by tailoring models to an institution’s patient population.

Tong et al. Use of Age-Adjusted Serum Creatinine in a Vancomycin Pharmacokinetic Model Decreases Predictive Performance in Elderly Patients

External validation of modified Goti model in patients over 65 years old with serum creatinine (SCr) less than 1 mg/dl using InsightRX Nova platform. Authors used actual SCr values instead of rounding up to 1mg/dl in these patients to assess the predictive performance compared to the traditional Goti model. Mean percentage error of predicted and observed levels was significantly reduced (-16.1% vs -31.6%) by using actual SCr rather than age-adjusted SCr values. This study serves an example of how continuous learning is very important for precision dosing and use of actual SCr in elderly patients may reduce bias and error in other models.

Lee et al. Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin

Cost-benefit analysis of institutional considerations related to vancomycin AUC-guided dosing including costs of Bayesian software and acute kidney injury (AKI) hospitalizations. Single-sample and two-sample AUC dosing compared to trough dosing saved an average of $2065 (US) and $846, respectively, per patient encounter. An institution would need to treat at least 41 patients with vancomycin for 48 hours to break even on Bayesian software costs, and may reduce rates of AKI, improve clinical outcomes, and reduce institutional costs.



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