Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Am J Med. 2012 Jan;125(1 Suppl):S3-13. doi: 10.1016/j.amjmed.2011.11.001.
Antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. In vitro susceptibility testing is often used to select agents with likely activity for a given infection, but perhaps its most important use is in identifying agents that will not work, i.e., to detect resistance. Standardized methods for reliable in vitro antifungal susceptibility testing are now available from the Clinical and Laboratory Standards Institute (CLSI) in the United States and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in Europe. Data gathered by these standardized tests are useful (in conjunction with other forms of data) for calculating clinical breakpoints and epidemiologic cutoff values (ECVs). Clinical breakpoints should be selected to optimize detection of non-wild-type (WT) strains of pathogens, and they should be species-specific and not divide WT distributions of important target species. ECVs are the most sensitive means of identifying strains with acquired resistance mechanisms. Various mechanisms can lead to acquired resistance of Candida species to azole drugs, the most common being induction of the efflux pumps encoded by the MDR or CDR genes, and acquisition of point mutations in the gene encoding for the target enzyme (ERG11). Acquired resistance of Candida species to echinocandins is typically mediated via acquisition of point mutations in the FKS genes encoding the major subunit of its target enzyme. Antifungal resistance is associated with elevated minimum inhibitory concentrations, poorer clinical outcomes, and breakthrough infections during antifungal treatment and prophylaxis. Candidemia due to Candida glabrata is becoming increasingly common, and C glabrata isolates are increasingly resistant to both azole and echinocandin antifungal agents. This situation requires continuing attention. Rates of azole-resistant Aspergillus fumigatus are currently low, but there are reports of emerging resistance, including multi-azole resistant isolates in parts of Europe.
抗真菌药物耐药性持续增长和演变，使患者管理变得复杂，尽管新的抗真菌药物不断问世。体外药敏试验常用于选择对特定感染可能有效的药物，但也许其最重要的用途是识别无效药物，即检测耐药性。美国临床和实验室标准协会（CLSI）和欧洲抗菌药物敏感性试验委员会（EUCAST）现已提供标准化的体外抗真菌药敏试验方法。这些标准化试验收集的数据（与其他形式的数据结合使用）可用于计算临床折点和流行病学临界值（ECV）。临床折点应选择优化检测非野生型（WT）病原体菌株，并且应具有种特异性，而不是划分重要靶物种的 WT 分布。ECV 是识别获得性耐药机制菌株的最敏感方法。各种机制可导致念珠菌对唑类药物产生获得性耐药，最常见的是诱导由 MDR 或 CDR 基因编码的外排泵，以及靶酶（ERG11）编码基因的点突变。念珠菌对棘白菌素类药物的获得性耐药通常通过 FKS 基因编码靶酶的主要亚基的点突变获得介导。抗真菌药物耐药性与最低抑菌浓度升高、临床结局较差以及抗真菌治疗和预防期间的突破性感染有关。光滑念珠菌引起的念珠菌血症越来越常见，且 C 光滑念珠菌对唑类和棘白菌素类抗真菌药物的耐药性日益增加。这种情况需要持续关注。烟曲霉唑类耐药率目前较低，但有报道称出现耐药性，包括欧洲部分地区多唑耐药株。
