Jan 182018

via cidrap

Microscopic yeast have been wreaking havoc in hospitals around the world—creeping into catheters, ventilator tubes, and IV lines—and causing deadly invasive infection. One culprit species, Candida auris, is resistant to many antifungals, meaning once a person is infected, there are limited treatment options. But in a recent Antimicrobial Agents and Chemotherapy study, researchers confirmed a new drug compound kills drug-resistant C. auris, both in the laboratory and in a mouse model that mimics human infection.

APX001, the prodrug of the active moiety APX001A, is currently in clinical development by Amplyx Pharmaceuticals. It works through a novel mechanism of action. Unlike other antifungal agents that poke holes in yeast cell membranes or inhibit sterol synthesis, the new drug targets an enzyme called Gwt1, which is required for anchoring critical proteins to the fungal cell wall. This means C. auris can’t grow properly and has a harder time forming drug-resistant fungal biofilms that are a stubborn source of hospital outbreaks. Gwt1 is highly conserved across fungal species, suggesting the new drug could treat a broad range of fungal infections.

“The drug is first in a new class of antifungals, which could help stave off drug resistance. Even the most troublesome strains are unlikely to have developed workarounds for its mechanism of action,” said study lead Mahmoud A. Ghannoum, PhD, professor of dermatology at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at Case Western Reserve University and University Hospitals Cleveland Medical Center.

In the new study, Ghannoum’s team tested the drug against 16 different C. auris strains, collected from infected patients in Germany, Japan, South Korea, and India. When they exposed the isolates to the new drug, they found it more potent than nine other currently available antifungals. According to the authors, the concentration of study drug needed to kill C. auris growing in laboratory dishes was “eight-fold lower than the next most active drug, anidulafungin, and more than 30-fold lower than all other compounds tested.”

The researchers also developed a new mouse model of invasive C. auris infection for the study. Said Ghannoum, “To help the discovery of effective drugs it will be necessary to have an animal model that mimics this infection. Our work helps this process in two ways: first we developed the needed animal model that mimics the infection caused by this devastating yeast, and second, we used the developed model to show the drug is effective in treating this infection.”

Ghannoum studied immunocompromised mice infected with C. auris via their tail vein—similar to very sick humans in hospitals who experience bloodstream infections. Infected mice treated with APX001 and anidulafungin had significant reductions in kidney and lung fungal burden two days post-treatment, compared to control animals. APX001 also significantly decreased fungal burden in the brain, consistent with brain penetration, whereas reduction with anidulafungin did not reach significance. The results suggest the new drug could help treat even the most invasive infections.

According to Ghannoum, the most exciting element of the study is that it brings a promising antifungal one step closer to patients. It helps lay the foundation for phase 2 clinical trials that study that study the safety and efficacy of new drugs in patients with fungal infections. There is an urgent need for such studies, as C. auris infection has become a serious threat to healthcare facilities worldwide—and resistance to commercially available antifungal drugs is rising.

“Limited treatment options calls for the development of new drugs that are effective against this devastating infection,” Ghannoum said. “We hope that we contributed in some way towards the development of new drugs.”

Learn more: New Antifungal Provides Hope in Fight Against Superbugs


The Latest on: Antifungal
  • Low enrollment for valley fever drug trial
    on February 24, 2018 at 5:10 am

    Some places have done better, but no one has done well.” The trial aims to answer this question: How effective is the early treatment of valley fever with the antifungal drug Fluconazole? The drug, long prescribed off-label to treat the disease ... […]

  • The Fungi That Cause Athlete's Foot Have Given Up On Sex
    on February 24, 2018 at 5:00 am

    Most importantly, it’s harder for these species to adapt to a changing environment. And sweeping changes that are cataclysmic—like, say, a powerful new antifungal drug—may even threaten the survival of the species. At the same time, asexual pests do ... […]

  • Connecting the dots between rapid sepsis diagnosis, patient outcomes, and healthcare costs
    on February 23, 2018 at 3:25 am

    “There are some early reports coming out that if you incorporate a test like this into antifungal stewardship – so for example, having a program that’s going to systematically look at test results and use negative results to stop antifungal treatment ... […]

  • Curcumin Believed to Be a Safe Post-Training Pain Manager
    on February 23, 2018 at 1:05 am

    antifungal and anti-inflammatory properties. There are many health care providers who recommend regular exercise to maintain optimum health. In addition to exercise, it is also important to practice a healthy diet. Pain and inflammation often take place ... […]

  • Is It Safe to Have Sex With a Yeast Infection?
    on February 22, 2018 at 6:41 pm

    First of all, can I live?! Second, yeast infections are typically pretty easy to treat, thanks to antifungal drugs. No matter which kind of yeast infection treatment you use, symptoms should calm down within a few days, Mary Jane Minkin, M.D., clinical ... […]

  • Dandruff Shampoos Have Gone Chic
    on February 22, 2018 at 12:47 pm

    It aims to combat flakes with peppermint oil, which gives off a refreshingly strong scent as you shampoo, and piroctone olamine, an antifungal compound that helps prevent the growth of a yeast that can lead to dandruff. It’s sold at Bergdorf Goodman and ... […]

  • Global antifungal therapeutics market illuminated by new report
    on February 21, 2018 at 9:53 pm

    The Global Antifungal Therapeutics Market report for the forecast period of 2018 – 2023 by MI Reports is a key insight into the Antifungal Therapeutics across various parameters. The solid research on the Antifungal Therapeutics is prepared with the aim ... […]

  • Vical Initiates Phase 2 Trial of VL-2397 Antifungal for Invasive Aspergillosis
    on February 20, 2018 at 8:50 am

    SAN DIEGO, CA, USA I February 20, 2018 I Vical Incorporated (Nasdaq:VICL) announced today the initiation of a Phase 2 trial of the Company’s VL-2397 novel antifungal compound. The multicenter, open label randomized clinical study, will compare the ... […]

  • Vical (VICL) Commences Phase 2 Trial of VL-2397 Antifungal for Invasive Aspergillosis
    on February 20, 2018 at 3:59 am

    Get instant alerts when news breaks on your stocks. Claim your 2-week free trial to StreetInsider Premium here. Vical Incorporated (NASDAQ: VICL) announced today the initiation of a Phase 2 trial of the Company’s VL-2397 novel antifungal compound. […]

  • Antifungal Treatment Market Top Segments and Key Trends 2018-2023; Says Sanofi, Merck & Co. Inc., Astellas
    on February 19, 2018 at 3:46 am

    The global antifungal treatment market is growing moderately and expected to grow at the same pace over the forecast period 2017-2013. Increasing number of patients with fungal diseases and growing prevalence of HIV are the key factors of the market growth. […]

via Google News and Bing News

Leave a Reply

%d bloggers like this: