Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, São Paulo State University/UNESP, SP Brazil.
Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI USA.
Expert Opin Pharmacother. 2021 May;22(7):867-887. doi: 10.1080/14656566.2021.1873951. Epub 2021 Feb 4.
: spp. are commensal yeasts capable of causing infections such as superficial, oral, vaginal, or systemic infections. Despite medical advances, the antifungal pharmacopeia remains limited and the development of alternative strategies is needed.: We discuss available treatments for spp. infections, highlighting advantages and limitations related to pharmacokinetics, cytotoxicity, and antimicrobial resistance. Moreover, we present new perspectives to improve the activity of the available antifungals, discussing their immunomodulatory potential and advances on drug delivery carriers. New therapeutic approaches are presented including recent synthesized antifungal compounds (Enchochleated-Amphotericin B, tetrazoles, rezafungin, enfumafungin, manogepix and arylamidine); drug repurposing using a diversity of antibacterial, antiviral and non-antimicrobial drugs; combination therapies with different compounds or photodynamic therapy; and innovations based on nano-particulate delivery systems.: With the lack of novel drugs, the available assets must be leveraged to their best advantage through modifications that enhance delivery, efficacy, and solubility. However, these efforts are met with continuous challenges presented by microbes in their infinite plight to resist and survive therapeutic drugs. The pharmacotherapeutic options in development need to focus on new antimicrobial targets. The success of each antimicrobial agent brings strategic insights to the next phased approach in treating spp. infections.
spp. 是共生酵母,能够引起感染,如浅表、口腔、阴道或全身感染。尽管医学取得了进步,但抗真菌药物仍然有限,需要开发替代策略。 我们讨论了 spp. 感染的可用治疗方法,强调了与药代动力学、细胞毒性和抗微生物耐药性相关的优缺点。此外,我们提出了改善现有抗真菌药物活性的新视角,讨论了它们的免疫调节潜力和药物传递载体的进展。介绍了新的治疗方法,包括最近合成的抗真菌化合物(包合两性霉素 B、四唑类、雷扎芬净、恩氟米芬净、曼戈匹酯和芳酰胺);使用多种抗菌、抗病毒和非抗菌药物进行药物再利用;不同化合物的联合治疗或光动力疗法;以及基于纳米颗粒传递系统的创新。 由于缺乏新的药物,必须通过增强药物输送、疗效和溶解度的修饰来充分利用现有资产。然而,这些努力面临着微生物不断抵抗和生存治疗药物的无限困境带来的持续挑战。开发中的治疗选择需要侧重于新的抗菌靶标。每种抗菌药物的成功都为治疗 spp. 感染的下一阶段方法提供了战略见解。