Public Health Research Institute, Rutgers Biomedical and Health Sciences, Newark, New Jersey.
Fungus Testing Laboratory, University of Texas Health Science Center, San Antonio.
J Infect Dis. 2017 Aug 15;216(suppl_3):S458-S465. doi: 10.1093/infdis/jix121.
Resistance to azoles and echinocandins has emerged as a significant factor affecting the clinical management of patients with invasive fungal infections. Immunosuppressed patients at high risk for invasive fungal infections often have prolonged or repeated exposure to antifungals resulting in either the well-documented selection of naturally occurring, less susceptible fungal species, or the in situ development of specific resistance mechanisms. Nucleic acid-based molecular diagnostics are particularly well suited for the rapid detection of low-abundance fungal pathogens and identification of the infecting pathogen to the genus and species levels, as well as assessment of resistance mechanisms. A wide range of molecular probing technologies involving real-time polymerase chain reaction (PCR) assays that facilitate direct analysis of a single infecting genome in a sterile blood specimen are available and have recently been commercialized (eg, Roche LightCycler SeptiFast and T2 Biosystems T2Candida). One of the exciting applications of molecular technology is the direct detection of specific resistance mechanisms that evolve during therapy. In principle, the detection of resistance mechanisms that have been independently validated to cause resistance provides a culture-independent biomarker for potential therapeutic failure. The emergence of real-time PCR assays utilizing allele-specific molecular detection technology that is highly sensitive, robust, and high-throughput has the potential to improve patient care by providing faster detection of drug-resistant infecting strains and to help inform therapeutic management.
唑类药物和棘白菌素类药物耐药性的出现已成为影响侵袭性真菌感染患者临床治疗的重要因素。免疫抑制的高危侵袭性真菌感染患者通常需要长期或反复接触抗真菌药物，从而导致天然存在的、敏感性较低的真菌物种的选择，或者特定耐药机制的原位发展。基于核酸的分子诊断特别适合于快速检测低丰度真菌病原体，并鉴定感染病原体的属和种水平，以及评估耐药机制。目前有多种涉及实时聚合酶链反应（PCR）检测的分子探测技术，这些技术可以方便地在无菌血液标本中直接分析单个感染基因组，并已最近商业化（例如罗氏 LightCycler SeptiFast 和 T2 Biosystems T2Candida）。分子技术的一个令人兴奋的应用是直接检测治疗过程中产生的特定耐药机制。原则上，检测已经独立验证可导致耐药性的耐药机制为潜在治疗失败提供了一种非培养依赖性的生物标志物。利用高度敏感、稳健和高通量的等位基因特异性分子检测技术的实时 PCR 检测方法具有通过更快地检测耐药感染株来改善患者护理并帮助指导治疗管理的潜力。
