A proposal of antifungal epidemiological cut-off values against Histoplasma capsulatum var. capsulatum based on the susceptibility of isolates from HIV-infected patients with disseminated histoplasmosis in Northeastern Brazil.


Brilhante RSN, Guedes GMM, da Silva MLQ, Castelo-Branco DSCM, Cordeiro RA, Sidrim JJC, Rocha MFG
Int J Antimicrob Agents. 2018 Mar 25. pii: S0924-8579(18)30094-3


Epidemiological cutoff values (ECV) have been used as a tool to detect the acquisition of resistance mechanisms to antifungal drugs. In this context, the objective of this study was to determine the epidemiological cutoff values for classic antifungals against Histoplasma capsulatum var. capsulatum isolates from HIV-infected patients with the diagnosis of disseminated histoplasmosis. Initially, the minimum inhibitory concentrations (MIC) for amphotericin B, itraconazole, fluconazole, voriconazole and caspofungin against 138 isolates of H. capsulatum in the filamentous form were determined by the broth microdilution method, then, the antifungal ECVs were calculated. MIC ranges were 0.0078-1 μg/mL for amphotericin B; 0.0005-0.0625 μg/mL for itraconazole; 2-≥256 μg/mL for fluconazole; 0.0078-1 μg/mL for voriconazole and 0.0156- ≥32 μg/mL for caspofungin. The obtained ECVs were 0.5; 0.0313; 128; 0.5 and 16 μg/mL for amphotericin B, itraconazole, fluconazole, voriconazole and caspofungin, respectively. The percentage of wild-type isolates was 96.38% for amphotericin B, 98.55% for itraconazole and 99.28% for fluconazole, voriconazole and caspofungin. Although these results do not cover all phylogenetic species of H. capsulatum, they bring important information on strains from Brazil. In addition, the assessed isolates were from HIV-positive patients, which may not reflect the antifungal ECVs against isolates from immunocompetent individuals and other sources. Finally, this study pioneers the initiative of establishing epidemiological cutoff values for five antifungal agents against H. capsulatum var. capsulatum, providing a criterion for the interpretation of susceptibility results; as well as a monitoring strategy for the emergence of antifungal resistance. KEYWORDS: Histoplasma capsulatum; antifungal drugs; epidemiological cutoff values; susceptibility