Emerging drugs and vaccines for Candidemia

Abstract

Summary Candidemia and other forms of invasive candidiasis are important causes of morbidity and mortality. The evolving challenge of antimicrobial resistance among fungal pathogens continues to highlight the need for potent, new antifungal agents. MEDLINE, EMBASE, Scopus, and Web of Science searches (up to January 2014) of the English-language literature were performed with the keywords “Candida” or “Candidemia” or “Candidiasis” and terms describing investigational drugs with activity against Candida spp. Conference abstracts and the bibliographies of pertinent articles were also reviewed for relevant reports. ClinicalTrials.gov was searched for relevant clinical trials. Currently available antifungal agents for the treatment of candidemia are summarized. Investigational antifungal agents with potential activity against Candida bloodstream infections and other forms of invasive candidiasis and vaccines for prevention of Candida infections are also reviewed as are selected antifungal agents no longer in development. Antifungal agents currently in clinical trials include isavuconazole, albaconazole, SCY-078, VT-1161, and T-2307. Further data are needed to determine the role of these compounds in the treatment of candidemia and other forms of invasive candidiasis. The progressive reduction in antimicrobial drug development may result in a decline in antifungal drug discovery. Still there remains a critical need for new antifungal agents to treat and prevent invasive candidiasis and other life-threatening mycoses.

Difficult but Not Impossible: in Search of an Anti-Candida Vaccine

“…However, all species can become opportunistic pathogens in immunocompromised populations, including transplant recipients, or individuals receiving chemotherapy and other cancer medications. Patients with central lines are exceptionally at risk, as Candida species are responsible for roughly 12% of all central line infections [4]. Likewise, neonatal patients are susceptible to infections due to their immature immune system.…”

“…According to a data set from a National Inpatient Survey in 2000, candidemia correlated to an additional 10.1 days of stay, resulting in an additional $40,000 in costs per patient. Hospitalization in infants proved even worse with an extra 21-day stay correlating to an extra $92,000+ in extra costs [4].…”

“…Development of antifungals, in comparison to medications that treat chronic conditions, often requires a high cost for a low rate of return. In the last 13 years, the FDA has approved only five antifungal agents, which can be categorized between the two classes of echinocandins (caspofungin, micafungin, and anidulafungin) and triazoles (voriconazole and posaconazole) [4]. Posaconazole is a newly approved generation of azoles that has a higher proven efficacy compared to the early-generation azoles, such as fluconazole and itraconazole.…”

New facets of antifungal therapy

“…Echinocandins are cyclic lipopeptide molecules derived from natural products that inhibit fungal b-1,3 glucan synthase, a major enzyme complex functioning in cell wall synthesis. [79][80][81] Similar to polyenes and azoles that target fungal ergosterol and its biosynthesis pathway, echinocandins have a unique drug target that is only present in fungi but not in mammalian cells, and thus these agents are much less toxic to humans. Echinocandins have several additional merits, including fungicidal activity against Candida species 82 , reduced emergence of drug-resistant isolates 79 , and most importantly, an improved safety profile and fewer drug interactions.…”

Exploiting mitochondria as targets for the development of new antifungals

“…43 Those in clinical trial include, VT-1161 (ergosterol synthesis inhibitor), SCY-078 (b-glucan inhibitor), and nikkomycin Z (chitin synthesis inhibitor). [46][47][48] The target of the fourth compound (F901318) is unknown, but it is in a phase 1 (biosafety) clinical trial that is underway in the US for the treatment of aspergillosis. Study results are not posted.…”