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.
Case Western Reserve University Medical Schoolcasemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=906&news_category=8

Probiotics may be a relatively safe, simple, and low-cost solution for preventing Clostridium difficile infections (CDI) in hospital settings, according to two studies. Both studies show that treating patients who received antibiotics with multi-strain probiotics, cut down on CDI incidence rates over time.
"While it’s not a perfect solution for a bacterium that has proven very difficult to prevent and treat, probiotics could offer patients another line of defence," said Bradley Johnston, PhD, associate professor of epidemiology at Dalhousie University in Canada and lead author of one of the studies. "We worked with clinical trialists from 12 countries that willingly shared their data with us to conduct what is known as an individual patient data meta-analysis and we demonstrated that we should be considering probiotics as a viable strategy for preventing CDI in patients."
The research led out of Dalhousie University in Canada conducted a synthesis of randomized controlled trials to determine whether probiotics reduced the odds of CDI in adults and children. It found that probiotics reduced the odds of CDI by about two-thirds in both their non-adjusted and adjusted models (adjusting for age, sex, hospitalization status, use of multiple antibiotics, and exposure to high-risk antibiotics). Additionally, they found that compared to no probiotics, multi-species probiotics were more beneficial than single-species probiotics.
This study analyzed 18 eligible randomized controlled trials that included patient data for 6,851 participants comparing probiotics to placebo or no treatment and that reported CDI as an outcome. Probiotics were especially effective among participants taking two or more antibiotics and in settings where the risk of CDI was greater than five percent.
A second project conducted by Cook County Health & Hospitals System at a separate tertiary care medical center, in which a single-center before-after quality improvement intervention was evaluated, found that probiotics provided a delayed benefit in reducing CDI. During the intervention period, there was a trend toward a lower incidence in CDI in the second six months, compared to the first six months. The authors speculate that the postponed benefit could be attributed to the time required for environmental contamination with spores of C. difficile to be brought under control.
"There is an expanding number of options to prevent or treat the often serious and costly infections caused by C. difficile," said William Trick, MD, a clinician at Cook County Health & Hospitals System and lead author of the study. "Probiotics are one option that is low cost, relatively safe, and likely beneficial in the long-run."
Trick and his team compared 12-month baseline and intervention periods. Patients in the study received capsules containing a three-strain probiotic mixture, to be taken within 12 hours of their antibiotics. The primary outcome of the study was the incidence of hospital-onset CDI among participants.
While this study showed the benefits of implementing probiotics as a strategy against CDI, it also highlighted the limitations in this approach. For instance, during a real-world quality improvement intervention, getting a probiotic agent to the right patients at the right time was challenging and led to incomplete use of the intervention. Also, the beneficial results are unlikely to match those reported in randomized controlled trials (RCTs). It is critical that interventions are tested in routine practice settings to uncover implementation challenges and to evaluate the replicability of results from RCTs in different settings.

The Society for Healthcare Epidemiology of America (SHEA)www.shea-online.org/index.php/journal-news/press-room/press-release-archives/588-probiotics-useful-in-the-fight-against-infection-prevention

In a first-of-its-kind study, Mount Sinai researchers are using adaptive optics (AO) to analyse retinal eye damage from the August solar eclipse on a cellular level. The research could help doctors develop a deeper understanding of this rare condition, called solar retinopathy, which has no currently accepted treatment.
Adaptive optics is a sophisticated technology that allows clinicians to examine microscopic structures of the eye in living patients with extreme detail in real time. Before the development of AO, researchers could only see this level of detail on glass slides with a microscope.
“We have never seen the cellular damage from an eclipse because this event rarely happens and we haven’t had this type of advanced technology to examine solar retinopathy until recently,” said lead investigator Avnish Deobhakta, MD, Assistant Professor of Ophthalmology at the Icahn School of Medicine at Mount Sinai. “NYEE is one of the few sites in North America with access to this technology, and using this to get an exact look at the patient’s retinal damage on such a precise level will help clinicians better understand the condition.”
Mount Sinai investigators used AO imaging on a patient who looked at the sun during the eclipse for 21 seconds without protective eyewear. Four hours later, the patient developed blurry distortion in both eyes and could only see the colour black. NYEE specialists examined her three days later and found she had burned a hole in her retinas and diagnosed her with solar retinopathy and photochemical burns.
Using this technology, researchers obtained high-resolution images of the damaged photoreceptors, which may provide a deeper understanding of the condition that could one day lead to the development of treatments.
“It’s exciting to be able to see such a correlation between the patient’s symptoms and the photoreceptor injury on a cellular level.  Hopefully this research allows us to potentially develop future therapies for solar retinopathy and other forms of photic injury to the retina,” said Chris Wu, MD, a resident physician at New York Eye and Ear Infirmary of Mount Sinai. “This study can prepare doctors and patients for the next eclipse in 2024, and make them more informed of the risks of directly viewing the sun without protective eyewear.”
Mount Sinai Health Systemhttps://tinyurl.com/y8cge588

Parkinson’s disease, a progressive brain disorder, is often tough to treat effectively because symptoms, such as tremors and walking difficulties, can vary dramatically over a period of days, or even hours.
To address this challenge, Johns Hopkins University computer scientists, working with an interdisciplinary team of experts from two other institutions, have developed a new approach that uses sensors on a smartphone to generate a score that reliably reflects symptom severity in patients with Parkinson’s disease.
In a study researchers from Johns Hopkins’ Whiting School of Engineering, the University of Rochester Medical Center, and Aston University in the U.K. reported that the severity of symptoms among Parkinson’s patients seen by neurologists aligned closely with those generated by their smartphone app.
Typically, patients with Parkinson’s disease are evaluated by medical specialists during three or four clinic visits annually with subjective assessments capturing only a brief snapshot of a patient’s fluctuating symptoms. In their homes, patients may also be asked to fill out a cumbersome 24-hour “motor diary” in which they keep a written record of their mobility, involuntary twisting movements and other Parkinson’s symptoms. The doctor then uses this self-reported or imprecise data to guide treatment.
In the new study, the researchers say patients could use a smartphone app to objectively monitor symptoms in their home and share this data to help doctors fine-tune their treatment.
E. Ray Dorsey, a University of Rochester Medical Center neurologist and a co-author of the research paper, said he welcomes the validation of Parkinson’s patient severity scores produced by the smartphone tests.
About six years ago, while doing medical research at Johns Hopkins, Dorsey was introduced to Suchi Saria, an assistant professor of computer science at the universityThe two researchers, along with some of Saria’s students, teamed up to find a way to monitor the health of Parkinson’s patients as easily as people with diabetes can check their glucose levels with a pinprick blood test.
The team members knew that neurologists evaluated their Parkinson’s patients by gathering information about how they moved, spoke and completed certain daily tasks. “Can we do this with a cellphone?” Saria wondered at the time. “We asked, ‘What are the tricks we can use to make that happen?’ ”
Using existing smartphone components such as its microphone, touch screen and accelerometer, the team members devised five simple tasks involving voice sensing, finger tapping, gait measurement, balance and reaction time. They turned this into a smartphone app called ‘HopkinsPD.’ Next, using a machine learning technique that the team devised, they were able to convert the data collected with these tests and turn that into an objective Parkinson’s disease severity score—a score that better reflected the overall severity of patients’ symptoms and how well they were responding to medication.
Johns Hopkins Universityreleases.jhu.edu/2018/04/05/smartphone-scores-can-help-doctors-track-severity-of-parkinsons-disease-symptoms/