Role and Interpretation of Antifungal Susceptibility Testing for the Management of Invasive Fungal Infections

Abstract

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate. Specifically, the utility of AST is limited by the delay in obtaining results and the lack of pharmacodynamic correlation between minimal inhibitory concentration (MIC) values and clinical outcome, particularly for molds. Clinical breakpoints for Candida spp. have been substantially revised over time and appear to be reliable for the detection of azole and echinocandin resistance and for outcome prediction, especially for non-neutropenic patients with candidemia. However, data are lacking for neutropenic patients with invasive candidiasis and some non-albicans Candida spp. (notably emerging Candida auris). For Aspergillus spp., AST is not routinely performed, but may be indicated according to the epidemiological context in the setting of emerging azole resistance among A. fumigatus. For non-Aspergillus molds (e.g., Mucorales, Fusarium or Scedosporium spp.), AST is not routinely recommended as interpretive criteria are lacking and many confounders, mainly host factors, seem to play a predominant role in responses to antifungal therapy. This review provides an overview of the pre-clinical and clinical pharmacodynamic data, which constitute the rationale for the use and interpretation of AST testing of yeasts and molds in clinical practice.

Changing Epidemiology of Invasive Fungal Disease in Allogeneic Hematopoietic Stem Cell Transplantation

“…Interestingly, this antifungal resistance is widely mediated by mutations in a specific gene (TR34/L98H) and could have occurred due to vast use of triazole fungicides in agriculture [2]. Besides this mutation, some Aspergillus species are known to have varying susceptibilities to different antifungal drugs [46]. For example, Aspergillus terreus is typically less susceptible to amphotericin B. Additionally, the use of molecular tools has permitted the description of new cryptic species among different Aspergillus species complexes.…”

Non-Candida Fungal Prosthetic Joint Infections

“…are characterized by intrinsic resistance to certain antifungal compounds [8]. Additionally, it must be noted that for a number of molds, laboratory methods indicating MICs are not standardized and unanimously accepted, while the immune status of the patient plays a major role [38].…”

“…However, the microbiological procedures used were not described in most of them. Moreover, since the present review spans almost four decades, it is understandable that identification techniques have evolved over time, ranging from simple microscopy, pathology, and culture to modern molecular methods [38]. Hence, although the information about the fungal cause of cases is sufficient, information about specific identification procedures has been inadequate.…”

Spondylodiscitis Caused by Aspergillus Species

“…Thus, it is of paramount importance to perform identification and susceptibility testing to obtain accurate MIC values following the Aspergillus isolation. It must be noted that according to EUCAST Antifungal Clinical Breakpoints from 2020 for a number of Aspergillus species, laboratory methods indicating MICs are standardized, while the immune status of the patient plays a major role [99,100].…”