Vancomycin AUC Implementation in Resource-Limited Settings and its Associated Difficulties

The 2020 guideline for therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus (MRSA) infections created sweeping changes compared to the 2009 guideline with the recommendation to utilize area under the curve (AUC)-based rather than trough-based monitoring.^1,2

Estimating AUC using 2-point measurements or Bayesian software is recommended, but each pose challenges particularly in settings with fewer resources. There has been little to no attention on implementation strategies in non-inpatient settings, e.g. rural facilities, outpatient parenteral antimicrobial therapy, rehabilitation centers, and others. Important variables such as populations served, regional resistant Gram-positive infection rates, vancomycin utilization, MRSA screening practices, and more must be considered, especially when weighing whether the pros and cons of AUC-based therapeutic drug monitoring (TDM) are “worth the squeeze” relative to the resources required for implementation and continual practice.³

Additionally, the topic has been the subject of recent and intense debate, given the efficacy data for serious MRSA infections and safety concerns (increased AKI risk) with AUC > 600mg*h/L, which may impact decisions on scope of implementation.^3-7 Implementation of AUC-based monitoring need not be an “all or none” phenomenon. Instead, implementation should be individualized, with a stringent focus on available resources including, but not limited to, personnel (Table 1), information technology resources, and facility type, with careful patient selection and exclusion during protocol design.⁸

Table 1 Key personnel and their roles in vancomycin AUC monitoring

Each method of AUC estimation is resource intensive in different ways. In resource-limited settings, pharmacists leading the transition to vancomycin AUC-based TDM may consider creative alternatives to costly Bayesian software. First-order equations can be calculated using less costly or even “free” programs, whether this is with a homegrown spreadsheet, a website on the facility’s intranet, integration into the electronic health record, or other modalities.⁸ Of note, two-point estimation may increase blood draws and the potential for erroneous or skipped peak concentrations. However, less frequent and more flexible timing of vancomycin blood draws are benefits of using Bayesian software, but it may not be most cost effective in low-volume settings. From a global cost perspective, a facility would break even after treating 68 patients with vancomycin for ≥ 48 hours using single-point Bayesian software (assumed $100,000 annual software cost) compared to 2-point AUC dosing according to a pharmacoeconomic analysis.¹⁰ It doesn’t account for the maintenance cost of consistent information technology team member support that is necessary for ongoing optimizations and troubleshooting.

Depending upon the setting, estimation of AUC using two-point measurements or Bayesian software may not be feasible or cost effective. Vancomycin use in the outpatient setting highlights some of the challenges and alternative methods of AUC-based monitoring. Upon hospital discharge, some centers have reverted back to an individualized trough target using the last trough associated with a therapeutic AUC, whereas others propose a lower trough target universally in lieu of AUC targets.^11,12 Another option is to target random serum concentrations of 20-25 mg/L (corresponding to AUC24 480-600 mg*h/L) while on continuous infusion vancomycin.¹

In summary, the transition to AUC-based monitoring, focused initially on serious MRSA infections, can be performed in numerous resource-limited settings. Free resources, continuing education, and spreadsheet tools are readily available online from professional organizations such as SIDP and MAD-ID to help small programs implement AUC-based monitoring. Once piloted, close assessment of effectiveness, patient safety, and cost, can be used to guide expansion of the program.

Additional Resources

1. Society of Infectious Diseases Pharmacists (SIDP), Main Website: https://www.sidp.org/Home
2. Making A Difference in Infectious Diseases (MAD-ID), Vancomycin AUC Dosing Resources: https://mad-id.org/vancomycin/
3. Vancomycin Therapeutic Drug Monitoring – The Times They Are a Changin’, ASHP Intensive Studies for Recertification: Pharmacotherapy (Cert # L219018) https://elearning.ashp.org/products/8730/intensive-studies-for-recertification-pharmacotherapy-cert-l219018
4. Includes patient cases with practical examples of AUC management
5. Stanford Antimicrobial Stewardship Website: Antimicrobial Dosing & Usage Guide, “Vancomycin” http://med.stanford.edu/bugsanddrugs/guidebook.html
6. Includes case tutorial, free AUC spreadsheet calculator, FAQs

Lina Meng is an infectious diseases and antimicrobial stewardship pharmacist with the Stanford Antimicrobial Safety and Sustainability Program. Dr. Meng has published and presented widely on vancomycin AUC implementation based on her experience with system-wide implementation at Stanford Health Care.

Eric Gregory is an infectious diseases and antimicrobial stewardship pharmacist at The University of Kansas Health System. Dr. Gregory's clinical and research interests include utilizing pharmacokinetic, pharmacodynamic, and antimicrobial stewardship principles to optimize care on the patient and institutional levels.

The Society of Infectious Diseases Pharmacists (SIDP) is an association of pharmacists and other allied healthcare professionals who are committed to promoting the appropriate use of antimicrobial agents and supporting practice, teaching, and research in infectious diseases. We aim to advance infectious diseases pharmacy and lead antimicrobial stewardship in order to optimize the care of patients. To learn more about SIDP, visit sidp.org.

References

1. Rybak MJ, Le J, Lodise TP, 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. Am J Health Syst Pharm. 2020;77(11):835-864.
2. Rybak MJ, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. 2009;66(1):82-98.
3. Lodise TP, Hall RG, Scheetz MH. Vancomycin area under the curve-guided dosing and monitoring: “Is the juice worth the squeeze”? Pharmacotherapy. 2020;40(12):1176-1179.
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5. 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. Clin Infect Dis. 2021. doi: 10.1093/cid/ciaa1744.
6. Jorgensen SCJ, Spellberg B, Shorr AF, Wright WF. Should therapeutic drug monitoring based on the vancomycin area under the concentration-time curve be standard for serious methicillin-resistant Staphylococcus aureus infections? - No. Clin Infect Dis. 2021. doi: 10.1093/cid/ciaa1743.
7. Burns AN, Goldman JL. A moving target-vancomycin therapeutic monitoring. J Pediatric Infect Dis Soc. 2020;9(4):474-478.
8. Heil EL, Claeys KC, Mynatt RP, et al. Making the change to area under the curve-based vancomycin dosing. Am J Health Syst Pharm. 2018;15;75(24):1986-1995.
9. Cole JL. Gap analysis for the conversion to area under the curve vancomycin monitoring in a small rural hospital. Fed Pract. 2020;37(S3):S12-S17.
10. Lee BV, Fong G, Bolaris M, et al. Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin. Clin Microbiol Infect. 2020 Nov 19:S1198-743X(20)30704-7. doi: 10.1016/j.cmi.2020.11.008. Epub ahead of print. PMID: 33221430.
11. Gregory ER, Burgess DR, Cotner SE, et al. Vancomycin area under the curve dosing and monitoring at an academic medical center: Transition strategies and lessons learned. J Pharm Pract. 2020;33(6):774-778.
12. Stewart JJ, Jorgensen SCJ, Dresser L, et al. A Canadian perspective on the revised 2020 ASHP-IDSA-PIDS-SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections. JAMMI. 2021. Doi: 10.3138/jammi-2020-0028.