Department of Clinical Microbiology, Trinity College Dublin, St James's Hospital Campus, Dublin 8, Ireland.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
J Antimicrob Chemother. 2022 Jul 28;77(8):2053-2073. doi: 10.1093/jac/dkac161.
The increasing incidence and changing epidemiology of invasive fungal infections continue to present many challenges to their effective management. The repertoire of antifungal drugs available for treatment is still limited although there are new antifungals on the horizon. Successful treatment of invasive mycoses is dependent on a mix of pathogen-, host- and antifungal drug-related factors. Laboratories need to be adept at detection of fungal pathogens in clinical samples in order to effectively guide treatment by identifying isolates with acquired drug resistance. While there are international guidelines on how to conduct in vitro antifungal susceptibility testing, these are not performed as widely as for bacterial pathogens. Furthermore, fungi generally are recovered in cultures more slowly than bacteria, and often cannot be cultured in the laboratory. Therefore, non-culture-based methods, including molecular tests, to detect fungi in clinical specimens are increasingly important in patient management and are becoming more reliable as technology improves. Molecular methods can also be used for detection of target gene mutations or other mechanisms that predict antifungal drug resistance. This review addresses acquired antifungal drug resistance in the principal human fungal pathogens and describes known resistance mechanisms and what in-house and commercial tools are available for their detection. It is emphasized that this approach should be complementary to culture-based susceptibility testing, given the range of mutations, resistance mechanisms and target genes that may be present in clinical isolates, but may not be included in current molecular assays.
侵袭性真菌感染的发病率不断上升和流行情况不断变化，这对其有效管理提出了许多挑战。尽管新的抗真菌药物不断涌现，但可用于治疗的抗真菌药物种类仍然有限。侵袭性真菌感染的成功治疗取决于病原体、宿主和抗真菌药物相关因素的综合作用。实验室需要善于从临床样本中检测真菌病原体，以便通过识别具有获得性耐药性的分离株来有效指导治疗。虽然有关于如何进行体外抗真菌药敏试验的国际指南，但这些指南的执行并不像针对细菌病原体那样广泛。此外，真菌的培养速度通常比细菌慢，而且常常不能在实验室中培养。因此，非培养方法，包括分子检测，用于检测临床标本中的真菌在患者管理中越来越重要，并且随着技术的提高，其可靠性也越来越高。分子方法还可用于检测预测抗真菌药物耐药性的靶基因突变或其他机制。本文综述了主要的人类真菌病原体获得性抗真菌药物耐药性，并描述了已知的耐药机制以及可用于检测这些机制的内部和商业工具。需要强调的是，鉴于临床分离株中可能存在多种突变、耐药机制和靶基因，但目前的分子检测可能无法涵盖这些内容，因此这种方法应该与基于培养的药敏试验相辅相成。
