‘Cost–benefit analysis comparing trough, two-level AUC, and Bayesian AUC dosing for vancomycin’: authors' reply
Authors: Brian V. Lee, Gary Fong, Michael Bolaris, Michael Neely, Emi Minejima, Amy Kang, Grace Lee, Cynthia L. Gong
Journal: Clinical Microbiology and Infection (2021)

We thank Dalton et al. for their interest in our article and model, and we appreciate the feedback and critique [[1]Lee B. Bolaris M. Neely M. Minejima E. Kang A. Lee G. et al.Cost–benefit analysis comparing trough, two-level AUC, and Bayesian AUC dosing for vancomycin.Clin Microbiol Infect. 2020; : 104743https://doi.org/10.1016/j.phrs.2020.104743Crossref Scopus (332) Google Scholar]. Our response to your letter will address the two primary concerns in sequential order: the first concern being the Bayesian AUC to trough comparison, and the second being two-level AUC to trough. We have gathered that your concern with our data from Neely et al. [[2]Neely M.N. Kato L. Youn G. Kraler L. Bayard D. Van Guilder M. et al.Prospective trial on the use of trough concentration versus area under the curve to determine therapeutic vancomycin dosing.Antimicrob Agents Chemother. 2018; 62: 1-12Crossref Scopus (180) Google Scholar] is that that the rates of acute kidney injury (AKI) are associated with different durations of therapy. In response to this, we operated under the conditions that: (a) different median durations of vancomycin therapy between AUC and trough dosing are not related to differences in baseline characteristics of the patients, as the same infections are being treated in year 1 to year 3 groups, and (b) we assume that the benefits of reduced median vancomycin duration form part of the clinical benefits and cost savings of the dosing method. Furthermore, although not reported in the original paper, the odds ratio for the combined Bayesian effect and each day of therapy on nephrotoxicity was 0.939 (95%CI 0.896, 0.983), and per day of vancomycin it was 1.002 (95%CI 1.000, 1.003). As a result, Bayesian dosing was associated with about a 6% (2–10%) reduction in nephrotoxicity adjusted for length of vancomycin therapy, which independently is not a large percentage, but in absolute numbers and savings can result in a significant value. Whether the decreased median duration of vancomycin therapy is related to significant improvements in antimicrobial stewardship from year 1 to year 3, or "more efficient therapeutic management with Bayesian control" as mentioned by the authors, is not known to us. For this reason, we use the total incidence of AKI and divide it among several time points as per the data from Hidayat et al. [[3]Hidayat L.K. Hsu D. Quist R. Shriner K. Wong-Beringer A. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections.Arch Intern Med. 2006; 166: 2138-2144Crossref PubMed Scopus (783) Google Scholar]. This was important for modelling purposes as well, in order to keep a comparison consistent between data of the few pieces of AUC literature available and the large amount of trough data from the past. However, we understand your concern about significant nephrotoxicity risk reduction extrapolated from this article; in response, we do still believe that the article demonstrated significant improvements from the year-1 group to the year-2 and -3 groups, as we expressed in our model, and this risk reduction was independent of therapy length, as mentioned above. To address the trough to two-point AUC section in the model, we did not use the values from Meng et al. as the main values for AKI, as we shared the same concern as yourself regarding the lack of statistical significance between the trough and non-Bayesian AUC group [[4]Meng L. Wong T. Huang S. Mui E. Nguyen V. Espinosa G. et al.Conversion from vancomycin trough concentration-guided dosing to area under the curve-guided dosing using two sample measurements in adults: implementation at an academic medical center.Pharmacotherapy. 2019; 39: 433-442Crossref PubMed Scopus (47) Google Scholar]. For this part of the model we used values from the hazard regression model by Finch et al., and used values from the study by Meng et al. to establish minimum possible bounds for the sensitivity analysis [[5]Finch N.A. Zasowksi E. Murray K. Mynatt R. Zhao J. Yost R. et al.A quasi-experimental to study the impact of vancomycin area under the concentration time curve guided dosing on vancomycin-associated nephrotoxicity.Antimicrob Ag. 2017; 61: e01293-e01317Crossref PubMed Scopus (127) Google Scholar]. We believe your analysis of our model and the current literature and data is keen and relevant, and we hope to have addressed your critique at least in part. While this model has limitations, including those you mentioned, we believe it to be a 'best interpretation' of the available literature which can only be more robust with further evidence, patient data, and institutional experiences. We stand by the core findings of the model: that incorporation of Bayesian AUC or two-level AUC vancomycin dosing provides a cost benefit to the institution over trough-based dosing in a majority of scenarios, and we hope to lessen hesitancy to do so. Dr Michael Neely MD, MSc, FCP receives license fees from InsightRx for use of BestDose. No other authors have any conflicts of interest to report. No external funding was received. Re: 'Cost–benefit analysis comparing trough, two-level AUC, and Bayesian AUC dosing for Vancomycin' by Lee et al.Clinical Microbiology and InfectionVol. 27Issue 6PreviewWe read with interest the article by Lee et al. [1] "Cost–benefit analysis comparing trough, two-level AUC, and Bayesian AUC dosing for vancomycin." Full-Text PDF Open ArchiveCost–benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycinClinical Microbiology and InfectionVol. 27Issue 9PreviewArea under the time–concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. Full-Text PDF