DEVELOPMENT OF INTERPRETIVE BREAKPOINTS FOR ANTIFUNGAL SUSCEPTIBILITYTESTING - CONCEPTUAL-FRAMEWORK AND ANALYSIS OF IN-VITRO IN-VIVO CORRELATION DATA FOR FLUCONAZOLE, ITRACONAZOLE, AND CANDIDA INFECTIONS

The availability of reproducible antifungal susceptibility testing met hods now permits analysis of data correlating susceptibility in vitro with outcome in vivo in order to define interpretive breakpoints. In t his paper, we have examined the conceptual framework underlying interp retation of antimicrobial susceptibility testing results and then used these ideas to drive analysis of data packages developed by the respe ctive manufacturers that correlate fluconazole and itraconazole MICs w ith outcome of candidal infections, Tentative fluconazole interpretive breakpoints for MICs determined by the National Committee for Clinica l Laboratory Standards' M27-T broth macrodilution methodology are prop osed: isolates for which MICs are less than or equal to 8 mu g/mL are susceptible to fluconazole, whereas those for which MICs are greater t han or equal to 64 mu g/mL appear resistant, Isolates for which the MI C of fluconazole is 16-32 mu g/mL are considered susceptible dependent upon dose (S-DD), on the basis of data indicating clinical response w hen >100 mg of fluconazole per day is given, These breakpoints do not, however, apply to Candida krusei, as it is considered inherently resi stant to fluconazole, Tentative interpretive MIC breakpoints for itrac onazole apply only to mucosal candidal infections and are as follows: susceptible, less than or equal to 0.125 mu g/mL; S-DD, 0.25-0.5 mu g/ mL; and resistant, greater than or equal to 1.0 mu g/mL. These tentati ve breakpoints are now open for public commentary.