1,2,3 for AUC Implementing the 2020

Vancomycin Dosing Guidelines Angharad Ratliff, PharmD

Greg Michaud, PharmD

Katie Presser, PharmD

Nick Smith, PharmD

Objectives

• Discuss the rationale for implementing AUC dosing with vancomycin

• Identify successful practices for transitioning from trough-based to AUC-based vancomycin dosing protocols

• Discuss common barriers and identify potential solutions for implementation

Overview

• Background – Why AUC dosing?

• How do I do this? Calculation tools

• When do I do this? Indications, MRSA vs non-MRSA infections, Special Populations, OPAT

• Who else is involved?

• Lab

• Nursing

• Pharmacy education

Introducing the Panelists

• Angharad – Alaska Regional Hospital

• Greg – MatSu Regional Medical Center

• Katie – Alaska Native Medical Center

• Nick – Providence Alaska Medical Center

Background: Why AUC?

2009 Guidelines

• AUC/MIC ≥ 400

• Trough of 15-20 mg/L as a surrogate

• Actual body weight for determining dosage

• Loading doses for severe infections

• Knowledge Gaps:

• Pediatrics

• Morbidly obese patients

• Renal failure

• Prolonged or continuous infusion

• Safety data for dosages > 3 g/day

• Safety and efficacy of targeted troughs 15-20mg/L

2020 Guidelines

• AUC/MIC 400-600

• AUC/MIC < 400 – encourages emergence of resistance

• Assume MIC of 1

• Vancomycin-associated AKI –

• Increased with AUC > 650

• Vancomycin monitoring

• Patients at high risk for nephrotoxicity

• Patients with unstable renal function

• Patients receiving prolonged courses of therapy ( > 3-5 days)

• Frequent or daily monitoring for unstable patients

• Weekly monitoring for stable patients

Methods of Calculating AUC

• Bayesian calculators

• Well-developed vancomycin population PK model + individual patient’s observed drug concentration

• Does not require steady state conditions

• Allows for trough-only sampling in select populations

• Limited information in special populations – obese, critically ill, pediatric, patients with unstable renal function

• First order PK analytic equations

• 2 steady state serum concentrations

• Lacks adaptive ability of Bayesian calculations

AUC Calculators

• Prov Excel calculator

• Precise PK

• Vancopk.com

• InsightRx

• Integration into EMR

• Turner, et al. Pharmacotherapy 2018

• Review of APK, BestDose, DoseMe, InsightRx, PrecisePK

• Considerations: integration into EMR, $$$, training required, adaptability

AUC Dosing Based Upon Indication?

• Guidelines – serious MRSA infections only

• Serious infections = bacteremia, sepsis, infective endocarditis, pneumonia, osteomyelitis, meningitis

• Easier implementation across the board?

• Increased workload on nursing/lab/pharmacy

• Methods to decrease workload?

• Which indications?

• Differentiating MRSA from non-MRSA infections

Special Patient Populations

• Obesity

• Increased risk of vancomycin-induced nephrotoxicity

• Vd increase not reliably associated with weight increase

• Loading dose (20-25mg/kg) recommended in patients with serious infections

• 3gm dose cap

• Max daily vancomycin doses of 4.5 gm/day

• 2 level analysis

Special Patient Populations

• Renal Failure

• Intermittent HD: pre-dialysis HD levels between 15-20mg/L achieves AUC 400-600

• Loading doses based upon actual body weight and if dose is to be administered intradialytically or post-dialysis

• Benefits of administering dose in dialysis vs. after dialysis

• Continuous renal replacement therapy (CRRT)

• Loading dose of 20-25 mg/kg actual body weight

• Initial maintenance dose: 7.5 – 10mg/kg q12h

• Serum concentration monitoring with 2 levels within 24 hours

• Dose based upon levels?

Long-term Therapy/Transition to Outpatient

• Surrogate trough monitoring

• When to use trough-only?

• Continuous infusion?

Nursing Considerations

• Nurses can be your make or break for AUC dosing

• Explaining the “WHY” is essential

• Plans for nursing education

• Concerns from nursing

Pharmacist Education

• Gaps in education

• Competency assessments

• On-hire

• On-going

• One-on-one meetings vs. group training sessions

Lab Considerations

• Labeling concerns:

• Education on moving from single level to 2 level analysis

• Terminology for lab orders: peak/trough, 2 randoms, AUC 1/AUC2

• Make sure you are looking at critical levels

• MIC concerns:

• CLSI allows for variability +/- 1 dilution

• E test method consistently higher MICs

• True rates of MIC of 2 much lower than previously reported

Open Forum

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