Abstract:
Multidrug resistance Candida auris is a dangerous fungal pathogen that is emerging at an alarming rate and posing serious threats to public health. C. auris is associated with nosocomial infections that cause invasive candidiasis in immunocompromised patients. Several antifungal drugs with distinct mechanisms of action are clinically approved for the treatment of fungal infections. The high rates of intrinsic and acquired drug resistance, particularly to azoles, reported in characterized clinical isolates of C. auris make treatment extremely problematic. In systemic infections, azoles are the first-line treatment for most Candida species; however, the increasing use of drugs results in the frequent emergence of drug resistance. More than 90% of the clinical isolates of C. auris is shown to be highly resistant to azole drugs especially fluconazole, with some strains (types) resistant to all three classes of commonly used antifungals. This presents a huge challenge for researchers in terms of completely understanding the molecular mechanism of azole resistance to develop more efficient drugs. Due to the scarcity of C. auris therapeutic alternatives, the development of successful drug combinations provides an alternative for clinical therapy. Taking advantage of various action mechanisms, such drugs in combination with azole are likely to have synergistic effects, improving treatment efficacy and overcoming C. auris azole drug resistance. In this review, we outline the current state of understanding about the mechanisms of azole resistance mainly fluconazole, and the current advancement in therapeutic approaches such as drug combinations toward C. auris infections.
摘要:
多药耐药耳念珠菌是一种危险的真菌病原体,正以惊人的速度出现,对公众健康构成严重威胁。金黄色葡萄球菌与在免疫受损患者中引起侵袭性念珠菌病的医院感染有关。具有不同作用机制的几种抗真菌药物在临床上被批准用于治疗真菌感染。内在和获得性耐药性的高发生率,特别是唑类,在以C.auris为特征的临床分离株中报道,使治疗非常成问题。在全身性感染中,唑类是大多数念珠菌属的一线治疗方法;然而,药物使用的增加导致耐药性的频繁出现。超过90%的C.auris的临床分离株显示对唑类药物特别是氟康唑具有高度耐药性,某些菌株(类型)对所有三类常用的抗真菌剂均具有抗性。这对研究人员提出了一个巨大的挑战,即完全理解唑类耐药的分子机制,以开发更有效的药物。由于金黄色葡萄球菌治疗替代品的稀缺,成功的药物组合的开发为临床治疗提供了替代方案.利用各种行动机制,这种药物与唑类药物联合使用可能具有协同作用,提高治疗效果,克服卡利斯唑耐药。在这次审查中,我们概述了对唑类耐药机制的理解现状,主要是氟康唑,以及目前在治疗方法方面的进展,例如针对金葡菌感染的药物组合。