Moreira Izabela de Mesquita Bárcia, Sousa Naira Sulany Oliveira de, Almeida Juan Diego Ribeiro de, Rosas Filho Robert Langlady Lira, Cruz Katia Santana, Matsuura Ani Beatriz Jackisch, Melhem Márcia de Souza Carvalho, Souza Érica Simplício de, Frickmann Hagen, Lacerda Marcus Vinícius Guimarães, Souza João Vicente Braga de
Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede BIONORTE, Manaus, AM, Brasil.
Instituto Nacional de Pesquisas da Amazônia, Manaus, AM, Brasil.
Rev Soc Bras Med Trop. 2025 Mar 24;58:e002002025. doi: 10.1590/0037-8682-0328-2024. eCollection 2025.
The reference methodology for evaluating antifungal susceptibility is based on determining the minimum inhibitory concentration (MIC), which is the lowest drug concentration capable of inhibiting fungal growth. However, such MIC data are insufficient to measure antifungal susceptibility if a strain is heteroresistant to the tested drug. In such cases, a minority subpopulation of fungal cells, originating from an initially susceptible lineage, can grow at antifungal drug concentrations above the MIC. In studies on fluconazole heteroresistance in Cryptococcus spp., chromosomal disomy has been shown to result in the overexpression of two genes located on chromosome 1 (Chr1) linked to antifungal resistance: ERG11 and AFR1. This review addresses the underlying mechanisms of antifungal resistance, the evolution of methods for determining antifungal susceptibility, and the clinical implications of Cryptococcus heteroresistance to fluconazole. The analysis of the findings indicated a correlation between heteroresistance and adverse clinical outcomes, although this observation still lacks definite confirmation in the literature. This highlights the need to implement more efficient therapeutic strategies and improve antifungal susceptibility and heteroresistance testing.
评估抗真菌药敏性的参考方法基于确定最低抑菌浓度（MIC），即能够抑制真菌生长的最低药物浓度。然而，如果菌株对受试药物存在异质性耐药，那么此类MIC数据就不足以衡量抗真菌药敏性。在这种情况下，源自最初敏感谱系的少数真菌细胞亚群能够在高于MIC的抗真菌药物浓度下生长。在关于隐球菌属中氟康唑异质性耐药的研究中，已表明染色体二体性会导致位于与抗真菌耐药性相关的1号染色体（Chr1）上的两个基因（ERG11和AFR1）过表达。本综述探讨了抗真菌耐药性的潜在机制、确定抗真菌药敏性方法的演变以及隐球菌对氟康唑异质性耐药的临床意义。对研究结果的分析表明异质性耐药与不良临床结局之间存在相关性，尽管这一观察结果在文献中仍缺乏明确证实。这凸显了实施更有效治疗策略以及改进抗真菌药敏性和异质性耐药检测的必要性。
