Guidelines

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

 

Efficacy 

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.

 

Safety 

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.

 

Special Populations

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.

 

Implementation

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.

 

Microbiology

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 Models

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.