Currently there are reference techniques for the in vitro determination of the sensitivity of fungi to antifungal agents (AFST) that allow to obtain reliable values of Minimum Inhibitory Concentration (MIC). These techniques developed either by the CLSI (Clinical Laboratory Standards Institute) in the USA [ 1 ] or by EUCAST (European Committee on Antimicrobial Susceptibility Testing) in Europe [ 2 ] therefore are robust and reproducible and allow comparison and aggregation MIC from different sources.
The analysis of the distribution of MIC for each species and antifungal used to define the "Epidemiological Cutoff Values" (ECOFFs for Europeans or ECVs for the Anglo-Saxon). The ECOFF is the MIC value which identifies the upper limit of a population of wild strains. A strain is defined as wild for a given species by the absence of acquired mechanism of resistance to an antifungal. The ECOFFs are determined from the MIC distribution histogram either by visual inspection or by mathematical methods. The ECOFF shows a characteristic of the population of wild strains and thus does not depend on the geographical origin, the host (human, animal, environment) or the period of collection of strains. This value is one of the parameters (among others) used to define clinical sensitivity thresholds (Clinical Breakpoints - CBPS) and is a sensitive indicator of the emergence of microbial resistance in epidemiological surveillance studies. Currently, ECOFFs were determined for many species of Candida and many antifungal, by EUCAST (http://www.eucast.org) and by CLSI [ 3-6 ].
The CBPS allow interpretation of CMI and therefore the categorization of sensitive strains - Intermediate - resistant. These thresholds are intended to have clinical relevance and not epidemiological or mechanistic. A strain is considered sensitive or resistant when the level of antifungal activity is associated with a high probability, respectively, of success or treatment failure. There is no formal relationship between ECOFF and CBP.Determining CBPS is made by expert committees and incorporates many parameters such as pharmacokinetics of antifungal, the ECOFF, experimental animal data, results of clinical studies, etc. Based on new data, CBPS may be revised over time. For example, very recently, CBs fluconazole and echinocandins have been extensively revised by the CLSI [ 7 , 8 ]. In some cases, such as caspofungin for which there is a large inter-laboratory variability [ 9 ], another molecule can be used as [class marker 10 ].
Full conference title:
- RICAI 34th (2014)