TIMC, Univ Grenoble Alpes, CNRS, Grenoble INP, Grenoble, France.
Parasitology-Mycology, CHU Grenoble Alpes, Grenoble, France.
Front Cell Infect Microbiol. 2021 Sep 10;11:720609. doi: 10.3389/fcimb.2021.720609. eCollection 2021.
Systemic antifungal agents are increasingly used for prevention or treatment of invasive fungal infections, whose prognosis remains poor. At the same time, emergence of resistant or even multi-resistant strains is of concern as the antifungal arsenal is limited. Antifungal susceptibility testing (AFST) is therefore of key importance for patient management and antifungal stewardship. Current AFST methods, including reference and commercial types, are based on growth inhibition in the presence of an antifungal, in liquid or solid media. They usually enable Minimal Inhibitory Concentrations (MIC) to be determined with direct clinical application. However, they are limited by a high turnaround time (TAT). Several innovative methods are currently under development to improve AFST. Techniques based on MALDI-TOF are promising with short TAT, but still need extensive clinical validation. Flow cytometry and computed imaging techniques detecting cellular responses to antifungal stress other than growth inhibition are also of interest. Finally, molecular detection of mutations associated with antifungal resistance is an intriguing alternative to standard AFST, already used in routine microbiology labs for detection of azole resistance in and even directly from samples. It is still restricted to known mutations. The development of Next Generation Sequencing (NGS) and whole-genome approaches may overcome this limitation in the near future. While promising approaches are under development, they are not perfect and the ideal AFST technique (user-friendly, reproducible, low-cost, fast and accurate) still needs to be set up routinely in clinical laboratories.
系统性抗真菌药物越来越多地用于预防或治疗侵袭性真菌感染，但其预后仍然很差。与此同时，由于抗真菌药物有限，耐药甚至多耐药菌株的出现令人担忧。因此，抗真菌药敏试验（AFST）对于患者管理和抗真菌管理至关重要。目前的 AFST 方法，包括参考和商业类型，都是基于在存在抗真菌药物的情况下在液体或固体培养基中的生长抑制。它们通常能够确定最小抑菌浓度（MIC），并直接应用于临床。然而，它们受到高周转时间（TAT）的限制。目前正在开发几种创新方法来改进 AFST。基于 MALDI-TOF 的技术具有短 TAT 的优势，但仍需要广泛的临床验证。流式细胞术和计算成像技术检测细胞对抗真菌应激的反应而不是生长抑制也很有意义。最后，与标准 AFST 相关的突变的分子检测是一种有吸引力的替代方法，已经在常规微生物学实验室中用于检测唑类耐药性，甚至可以直接从样本中检测。它仍然限于已知的突变。下一代测序（NGS）和全基因组方法的发展可能在不久的将来克服这一限制。虽然有前途的方法正在开发中，但它们并不完美，理想的 AFST 技术（用户友好、可重复、低成本、快速和准确）仍需要在临床实验室中常规建立。
