Background: Recent studies evaluating area under the concentration time curve (AUC)-guided vancomycin dosing have reported reduced drug exposure and nephrotoxicity as compared with traditional trough-guided (target 15-20 mg/L) dosing for invasive infections, but studies exploring the relationship between vancomycin trough concentration and AUC remain limited.
Methods: This was a retrospective observational study performed at two hospitals within a large health system. Patients receiving AUC-guided vancomycin dosing for a presumed or confirmed invasive staphylococcal infection between December 1, 2016 and July 31, 2017 were evaluated. Two steady-state serum vancomycin levels were obtained in each patient and used to determine the 24-hour (hr) AUC/MIC ratio; the AUC/MIC target was >600 mg/L*hr for endocarditis and >400 mg/L*hr for all other sources. The relationship between trough and AUC was explored using the Pearson product-moment correlation coefficient. Patient demographics and dosing details were also collected.
Results: Thirty-four patients were included in the study, with two patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an ICU (91.2%) and 85.3% of patients had bacteremia, pneumonia or endocarditis. An organism was recovered from 28 patients (82.3%) of which 21 (75%) had a vancomycin MIC of 1mg/L and 25 were S. aureus (89.3%). The mean vancomycin trough was 16.6 ± 6.1mg/L and the mean AUC/MIC was 588 ± 156 mg/L*hr. There was a strong correlation between vancomycin trough and 24-hr AUC (R2=0.731; p<0.001; Figure 1). The rate of 24-hr vancomycin AUC/MIC target attainment was 91.2% (n=31/34). Among patients with a trough >9 mg/L, 100% (n=33) achieved AUC/MIC values >400 mg/L*hr and 94% were >500 mg/L*hr.
Conclusion: Targeting a vancomycin trough between 15 and 20 mg/L frequently results in an AUC/MIC in excess of the target identified for efficacy. Considering the strong correlation observed between trough and AUC alongside practical challenges associated with wide-scale implementation of AUC monitoring, a reduced target trough in conjunction with targeted application of AUC-guided dosing warrants further evaluation.
R. Servais, None
C. F. Brummitt, None
T. J. Dilworth, None