Breakpoints for posaconazole susceptibility testing: background and discussion about the need of establishing values

Abstract

Posaconazole is a new antifungal agent, which exhibits a broad spectrum of activity against fungi including Aspergillus terreus, some zygomycetes and dematiaceous fungi. Out of the group of triazole antifungal agents, it is the only compound for which interpretive breakpoints have not been established have not yet been established for Candida spp. As reliable breakpoints are useful in the practical management of patients with fungal infections, it is desirable to establish the same for all available substances. However, the underlying data of the existing breakpoints for other antifungal agents are of varying quality because of limited clinical data available. Furthermore, these breakpoints are not equally suitable for all testing methods available and they may not be suitable for all species to be tested. From the practical point of view, it is therefore important not only to establish breakpoints for the reference method but also for the inexpensive and easy to perform testing methods, which are suitable for smaller laboratories.

In vitro Antifungal Susceptibility of Agents for Superficial Phaeohyphomycosis

“…4 Previous data showing MIC > 8 μg/mL suggests non--dermatophytic species are resistant for ITC. 30 According to Yew et al, 31 dematiaceous fungi present high susceptibility to AMB, ITC and VRC (MIC ≤ 1 μg/mL), however, low sensitivity to FLC (MIC ≥ 4 μg/mL).…”

Invasive Candidiasis and the Utility of Antifungal Susceptibility Testing in the ICU

“…2,24 Breakpoints have also been proposed for posaconazole, S 1 mcg/mL and R > 4 mcg/mL. 15 Susceptibility breakpoints have been established for the echinocandins caspofungin, anidulafungin, and micafungin based on in vitro data from large-scale surveillance studies,…”

“…This broader activity may be advantageous in some high-risk critically ill patients. 3,8,15 The echinocandins (caspofungin, micafungin, anidulafungin) are the newest class of antifungal agents. They are fungicidal against C. albicans and some non-albicans species.…”

“…The Clinical Laboratory Standards Institute (CLSI), formally NCCLS, at that time proposed standardized microbroth dilution methodology and susceptibility breakpoints in the document M27-A, which has since been updated in 2002 as M27-A2, with the most recent update in 2008 as M27-A3. 15,24,25 The microbroth dilution method is the gold-standard technique, but it can be very labor intensive and costly for hospital clinical laboratories. Other methods such as agar disk diffusion and Etest (AB Biodisk, Solna, Sweden) are much simpler to perform and have shown comparable results to microbroth dilution.…”