Reply to Day et al

To the Editor—We appreciate the comments from Day et al about our manuscript, “Core Recommendations for Antifungal Stewardship” which is intended to provide a conceptual framework regarding the challenges in antifungal stewardship (AFS) and how these challenges can be addressed [1]. Development and implementation of institutional care pathways or treatment bundles are cited as an example of a method to increase timely performance of certain diagnostic tests, procedures, and treatment to maximize patient outcomes.

We present sample bundles for candidemia and aspergillosis only as illustrative examples of this notion. Published studies evaluating the impact of bundles/pathways for candidemia patients have included ophthalmological exams, as recommended by the Infectious Diseases Society of America and European Society of Clinical Microbiology and Infectious Diseases [2, 3]. Although there has been heterogeneity in achievement of individual bundle elements in published studies, these investigations demonstrated that bundle implementation was associated with better outcomes such as mortality [4–7], clinical success [6], or appropriate timing, selection and/or duration of antifungal therapy [8, 9]. As stated in our review, there may be differences in merit and relative contributions for individual bundle elements. For example, as it relates to performing routine ophthalmologic exams in patients with candidemia, many nuances exist including timing of the exam, suspicion for metastatic Candida infection and not only fungemia, availability of special equipment, and skill level of the examiner. Our review clearly was not intended to discuss or prescribe the particular elements of routine ophthalmologic results of these bundles. Nevertheless, we are unaware of any specific data suggesting that ophthalmologic exams worsen outcomes of patients with candidemia. The recently developed EQUAL score for candidemia attempts to address some of these concerns, and still includes ophthalmologic examinations as a component [10]. At the local level, there should be some flexibility to allow for the use of the elements of stewardship bundles as a foundation, while adapting to reflect local epidemiology, patient-specific factors, logistics, and available resources. However, we do not believe the available data overwhelmingly support dissociating individual elements from the evidence-based bundles.

A major goal of our recommendations was to promote multidisciplinary care and a team approach to AFS. Accordingly, we value the input of our ophthalmology colleagues and welcome collaborative approaches to developing and implementing AFS programs, as well as developing more refined clinical/diagnostic screening tools that could help reduce unnecessary invasive/diagnostic exams.

Notes

Financial support. This work was supported by National Institutes for Health-National Cancer Institute Cancer Center CORE Support (grant number 16672); and D. P. K. is supported by the Robert C Hickey Endowed Chair for Cancer Research.

Potential conflicts of interest. M. D. J. reports personal fees from Astellas, Cidara, Merck, Paratek, Pfizer, Theratechnologies, and UpToDate, and grants from Astellas, Scynexis, Charles River Laboratories, and Merck & Co, outside the submitted work. R. E. L. reports grants from Merck, and personal fees from Gilead and Cidara Therapeutics, outside the submitted work. E. S. D. A. reports personal fees from The Joint Commission Resources and UptoDate, outside the submitted work. J. R. P. reports grants from Astellas, Merck, Pfizer, Minnetronix, and Amplyx; advisory board honoraria from Merck, F2G, Ampili, and Matinas; and advisory board/consulting honoraria from Scynexis, outside the submitted work. D. P. K. reports research support from Gilead and Astellas Pharma and honoraria for lectures from Gilead; has served as a consultant for Astellas Pharma, and is a member of the data review committee of Cidara and Abbie, Inc.