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

作者：Nogueira Brilhante Raimunda Samia; de Melo Guedes Glaucia Morgana; Queiroz da Silva Maria Lucilene; Collares Maia Castelo Branco Debora Souza; Cordeiro Rossana de Aguiar; Costa Sidrim Jose Julio; Gadelha Rocha Marcos Fabio

来源：International Journal of Antimicrobial Agents, 2018, 52(2): 272-277.

DOI：10.1016/j.ijantimicag.2018.03.017

• Histoplasma capsulatum
• Antifungal drugs
• Susceptibility
• Epidemiological cut-off values

Epidemiological cut-offvalues (ECVs) 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 ECVs for classic antifungals against Histoplasma capsulatum var. capsulatum isolates from human immunodeficiency virus (HIV)-infected patients with a diagnosis of disseminated histoplasmosis. First, minimum inhibitory concentrations (MICs) for amphotericin B (AmB), itraconazole (ITR), fluconazole (FLU), voriconazole (VCZ) and caspofungin (CAS) were determined against 138 H. capsulatum isolates in the filamentous form by the broth microdilution method; antifungal ECVs were then calculated. MIC ranges were 0.0078-1 mu g/mL for AmB, 0.0005-0.0625 mu g/mL for ITR, 2 to >= 256 mu g/mL for FLU, 0.0078-1 mu g/mL for VCZ and <= 0.0156 to >= 32 mu g/mL for CAS. The obtained ECVs were 0.5, 0.0313, 128, 0.5 and 16 mu g/mL for AmB, ITR, FLU, VCZ and CAS, respectively. The percentage of wild-type isolates was 96.4% for AmB, 98.6% for ITR and 99.3% for FLU, VCZ and CAS. 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 or from other sources. Finally, this study pioneers the initiative of establishing ECVs 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.

• 出版日期2018-8