Methods
VHSO is a 52-bed US Department of Veterans Affairs primary care hospital. The pharmacy and laboratory are staffed 24 hours each day. There is 1 clinical pharmacy specialist (CPS) available for therapeutic drug monitoring consults Monday through Friday between the hours of 7:30 AM and 4:00 PM. No partial full-time equivalent employees were added for this conversion. Pharmacy-driven vancomycin dosing and monitoring is conducted on a collaborative basis, with pharmacy managing the majority of vancomycin treated patients. Night and weekend pharmacy staff provide cross-coverage on vancomycin consultations. Laboratory orders and medication dosage adjustments fall within the CPS scope of practice. Nurses do not perform laboratory draws for therapeutic drug monitoring; this is done solely by phlebotomists. There is no infectious diseases specialist at the facility to champion antibiotic dosing initiatives.
The implementation strategy largely reflected those outlined from tertiary care centers.5,6 First, key personnel from the laboratory department met to discuss this practice change and to add vancomycin peaks to the ordering menu. A critical value was set at 40 mcg/ml. Vancomycin troughs and random levels already were orderable items. A comment field was added to all laboratory orders for further clarification. Verbiage was added to laboratory reports in the computerized medical record to assist clinicians in determining the appropriateness of the level. This was followed by an educational email to both the nursing and laboratory departments explaining the practice change and included a link to the Pharmacy Joe “Vancomycin Dosing by AUC:MIC Instead of Trough-level” podcast (www.pharmacyjoe.com episode 356).
The pharmacy department received an interactive 30-minute presentation, followed immediately by a group activity to discuss practice problems. This presentation was condensed, recorded, and emailed to all VHSO pharmacists. A shared folder contained pertinent material on AUC monitoring.
Finally, an interactive presentation was set up for hospitalists and a video teleconferencing was conducted for rotating medical residents. Both the podcast and recorded presentation were emailed to the entire medical staff with a brief introduction of the practice change. Additionally, the transition process was added as a standing item on the monthly antimicrobial stewardship meeting agenda.
The standardized pharmacokinetic model at the study facility consisted of a vancomycin volume of distribution of 0.7 mg/kg and elimination rate constant (Ke) by Matzke and colleagues for total daily dose calculations.12 Obese patients (BMI ≥ 30) undergo alternative clearance equations described by Crass and colleagues.13 Cockcroft-Gault methods using ideal body weight (or actual body weight if < ideal body weight) are used for determining creatinine clearance. In patients aged ≥ 65 years with a serum creatinine < 1.0 mg/dL, facility guidance was to round serum creatinine up to 1.0 mg/dL. Loading doses were determined on a case-by-case basis with a cap of 2,000 mg, maintenance doses were rounded to the nearest 250 mg.
Vancomycin levels typically are drawn at steady state and analyzed using the logarithmic trapezoidal rule.14 The pharmacy and medical staff were educated to provide details on timing and coordination in nursing and laboratory orders (Table 1). Two-level AUC monitoring typically is not performed in patients with acute renal failure, expected duration of therapy < 72 hours, urinary tract infections, skin and soft tissue infections, or in renal replacement therapy.5
This gap analysis consisted of a retrospective chart review of vancomycin levels ordered after the implementation of AUC-based monitoring to determine the effectiveness of the transition. Three months of data were collected between April 2019 and June 2019. Vancomycin levels were deemed either appropriate or inappropriate based on timing and type (peak, trough, or random) of the laboratory test in relation to the previously administered vancomycin dose. Appropriate peaks were drawn within 2 hours after the end of infusion and troughs at least 1 half-life after the dose or just prior to the next dose and within the same dosing interval as the peak. Tests drawn outside of the specified time range, trough-only laboratory tests, or those drawn after vancomycin had been discontinued were considered inappropriate. Peaks and troughs drawn from separate dosing intervals also were considered inappropriate. Random levels were considered appropriate only if they fit the clinical context in acute renal failure or renal replacement therapy. An effective transition was defined as ≥ 80% of all vancomycin treated patients monitored with AUC methods rather than trough-based methods.
Inclusion criteria included all vancomycin levels ordered during the study period with no exclusions. The primary endpoint was the proportion of vancomycin levels drawn appropriately. Secondary endpoints were the proportion of AUC24 calculations within therapeutic range and a stratification of reasons for inappropriate levels. Descriptive statistics were collected to describe the scope of the project. Levels drawn from various shifts were compared (ie, day, night, or weekend). Calculated AUC24 levels between 400 and 600 mg.h/L were considered therapeutic unless treating CNS infection (600-700 mg.h/L). Given the operational outcomes (rather than clinical outcomes) and no comparator group, patient specific data were not collected.
Descriptive statistics without further analysis were used to describe proportions. The goal level for compliance was set at 100%. These methods were reviewed by the VHSO Institutional Review Board and granted nonresearch status, waiving the requirement for informed consent.