Determination of the relationship between vancomycin trough concentrations and the AUC/MIC Dosing
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Date
2020-07-15
Authors
Ing, Nathan
McQueen, Joe
Nadeau, Lynn
Hussein, Abdulkadir A.
Journal Title
Journal ISSN
Volume Title
Publisher
University of Waterloo
Abstract
Rationale: The recently revised guidelines for the therapeutic monitoring of
vancomycin recommend targeting an AUC/MIC of 400-600 for serious
methicillin-resistant Staphylococcus aureus (MRSA) infections. The
feasibility of transitioning from trough-based dosing to dosing by AUC/MIC
warrants further study as the latter method has been shown to require
additional pharmacist training and increased costs secondary to laboratory
monitoring and specialty software.
Methods: This was a prospective, non-randomized, single-centre trial
conducted over eight months. Adult inpatients receiving vancomycin for
greater than three days for the treatment of serious MRSA infections were
included in the study. The AUC/MIC was calculated using two-point
pharmacokinetic equations from peak and trough concentrations. The primary
outcome was to determine the relationship between vancomycin trough
concentrations and the AUC/MIC. Secondary objectives were to assess the
difference in vancomycin doses and rates of acute kidney injury (AKI) between
traditional trough-based dosing and AUC/MIC dosing.
Results: 234 patients received vancomycin over the study period and 32
patients met the inclusion criteria; 36 sets of vancomycin levels were
obtained. Sites of infection included skin and soft tissue (31.2%),
bacteremia (21.9%), pneumonia (18.8%), osteomyelitis (15.6%) and
miscellaneous (12.5%). Vancomycin trough concentrations of 10.8-16.1 mg/L
correlated to an AUC/MIC of 400-600 with 95% probability (r2=0.75). The
average total daily doses for trough-based and AUC/MIC dosing were 1590.28 mg
and 1281.25 mg, respectively. The mean difference in dose between the two
dosing strategies was 309 mg (p=0.179). There were no significant differences
in the rates of AKI between trough-based dosing and dosing by AUC/MIC
[OR=1.791; 95% CI (0.119,48.048)].
Conclusion: On average, vancomycin trough concentrations of approximately
11-16 mg/L correlated strongly with an AUC/MIC of 400-600, suggesting that
adopting the cumbersome and costly strategy of AUC/MIC targeted dosing may be
unnecessary, but further study is required. This correlation also suggests
that aggressively targeting vancomycin troughs of 15-20 mg/L, as previously
recommended, is unwarranted. Average daily doses and rates of AKI did not
significantly differ between trough-based dosing and dosing by AUC/MIC.
Description
Keywords
vancomycin, AUC/MIC, area under the curve, minimum inhibitory concentration