Antifungal Resistance among Less Prevalent Candida Non-albicans and Other Yeasts versus Established and under Development Agents: A Literature Review

Abstract

Fungal diseases and antifungal resistance continue to increase, including those caused by rare or emerging species. However, the majority of the published in vitro susceptibility data are for the most common fungal species. We reviewed the literature in order to pool reference minimal inhibitory concentration (MIC) data (Clinical and Laboratory Standards Institute—CLSI and European Committee on Antimicrobial Susceptibility—EUCAST) for rare/non-prevalent Candida and other yeast species. MIC results were compared with those for Candida albicans, C. glabrata, and C. krusei. Data were listed for twenty rare and emerging Candida spp., including C. auris, as well as two Cryptococcus spp., two Trichosporon spp., Saccharomyces cerevisiae and five Malassezia spp. The best detectors of antimicrobial resistance are the breakpoints, which are not available for the less common Candida species. However, epidemiological cutoff values (ECVs/ECOFFs) have been calculated using merely in vitro data for both reference methods for various non-prevalent yeasts and recently the CLSI has established ECVs for other Candida species. The ECV could identify the non-wild type (NWT or mutants) isolates with known resistance mechanisms. Utilizing these ECVs, we were able to report additional percentages of NWT, especially for non-prevalent species, by analyzing the MIC distributions in the literature. In addition, since several antifungal drugs are under development, we are listing MIC data for some of these agents.

The Mould War: Developing an Armamentarium against Fungal Pathogens Utilising Thymoquinone, Ocimene, and Miramistin within Bacterial Cellulose Matrices

“…The data collected during this study have highlighted the efficacy and high in vitro tolerability of our agents in use as an antifungal and would benefit greatly from further investigation. As we have highlighted in this study, the importance of utilising naturally occurring products is paramount in fighting the burdening issue of antifungal resistance [74,75]. It is clear that pharmaceutical agents such as amphotericin B are usually accompanied by severe side effects that make their use intolerable to individuals while having low efficacy to their target organism [76,77].…”

Exposure of Cryptococcus neoformans to Seven Commonly Used Agricultural Azole Fungicides Induces Resistance to Fluconazole as Well as Cross-Resistance to Voriconazole, Posaconazole, Itraconazole and Isavuconazole

“…For the C. neoformans species complex, no break-point is available. Epidemiological cut-off (ECV) values to discriminate wild-type strains from strains with reduced susceptibility to antifungals (i.e., resistant phenotype) were used for the medical azole molecules with the following values: ECV (FCZ) = 8 µg/mL, ECV (POS) = 0.25 µg/mL, ECV (ISA) = 0.06 µg/mL, ECV (ITR) = 0.25 µg/mL and ECV (VOR) = 0.12 µg/mL [ 43 , 44 , 45 , 46 ]. Unfortunately, as such values do not exist for pesticides, no such classification could be conducted in regard to agricultural azoles.…”

Synthesis and Evaluation of the Antifungal and Toxicological Activity of Nitrofuran Derivatives

“…However, reports of fungal resistance have already been described for the standard antifungal classes used in therapy. Regarding polyenes, mutations change the principal sterol in the membrane, affecting the polyene binding, whereas, for the azole class, mutations in the gene encoding the target protein, or its overexpression, as well as other resistance mechanisms can occur [ 10 , 11 , 12 ]. In addition, reports of high toxicity and drug interactions are prevalent and have been described for these antifungal classes [ 13 , 14 , 15 ].…”