Candida auris , a new multidrug-resistant Candida spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16 C. auris isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β- d -glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of C. auris . Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of Candida albicans ( P = 0.01). C. auris isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC 90 of 1 mg/liter against C. auris and caused complete inhibition of the growth of C. auris and C. albicans . Scanning electron microscopy analysis showed that SCY-078 interrupted C. auris cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control ( P < 0.05 for both comparisons). Our study shows that C. auris expresses several virulence determinants (albeit to a lesser extent than C. albicans ) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against C. auris , indicating that further evaluation of this antifungal is warranted.
10 August 2017 in Infection Control & Hospital Epidemiology
Contaminated surfaces are a suspected source for dissemination of the globally emerging pathogen Candida auris. In laboratory testing, sporicidal and improved hydrogen peroxide disinfectants were highly effective against C. auris, C. glabrata, and C. albicans. The widely used quaternary ammonium disinfectants exhibited relatively poor activity against all of the Candida species.Infect Control Hosp Epidemiol 2017;38:1240–1243
1 March 2018 in Antimicrobial Agents and Chemotherapy
Candida auris is an emerging multidrug-resistant yeast that has been responsible for invasive infections associated with high morbidity and mortality. C. auris strains often demonstrate high fluconazole and amphotericin B MIC values, and some strains are resistant to all three major antifungal classes. We evaluated the susceptibility of 16 C. auris clinical strains, isolated from a wide geographical area, to 10 antifungal agents, including APX001A, a novel agent that inhibits the fungal protein Gwt1 (glycosylphosphatidylinositol-anchored wall transfer protein 1). APX001A demonstrated significantly lower MIC 50 and MIC 90 values (0.004 and 0.031 μg/ml, respectively) than all other agents tested. The efficacy of the prodrug APX001 was evaluated in an immunocompromised murine model of disseminated C. auris infection. Significant efficacy (80 to 100% survival) was observed in all three APX001 treatment groups versus 50% survival for the anidulafungin treatment group. In addition, APX001 showed a significant log reduction in CFU counts in kidney, lung, and brain tissue (1.03 to 1.83) versus the vehicle control. Anidulafungin also showed a significant log reduction in CFU in the kidneys and lungs (1.5 and 1.62, respectively) but did not impact brain CFU. These data support further clinical evaluation of this new antifungal agent.
21 November 2017 in Infection Control & Hospital Epidemiology
Mobile ultraviolet-C (UV-C) light room decontamination devices are frequently used as an adjunct to standard cleaning in healthcare facilities, but their efficacy in killing Candida species is not clear. In laboratory testing, the emerging multidrug-resistant Candida auris and 2 other Candida species were significantly less susceptible to killing by UV-C than methicillin-resistant Staphylococcus aureus.Infect Control Hosp Epidemiol 2018;39:94–96
1 January 2018 in Journal of Antimicrobial Chemotherapy
Echinocandins have been in use for over 15 years, starting with the first approval in 2001. Current trends, such as increasing resistance to fluconazole and shifts toward non-albicans spp. of Candida, suggest a growing role for echinocandins, as reflected by recent (2016) updates to guidelines that recommend echinocandins as first-line treatment for candidaemia. The efficacy, tolerability, and safety of echinocandins and their target site of action (1,3-β-d-glucan synthesis) have prompted research into potential new uses, such as for treatment of biofilm infections, MDR Candida auris and dermatophytes. Moreover, new mycobiome discoveries linking inflammatory bowel disease (IBD; for instance Crohn’s disease) to fungi have led to preliminary but encouraging data regarding echinocandin therapy and treatment of IBD. In this article, we will review the available evidence and potential utility of echinocandins and 1,3-β-d-glucan synthesis inhibition in these areas of emerging interest.
The survival of Salmonella on dried chamomile flowers, peppermint leaves, and green tea leaves stored under different conditions was examined. Survival and growth of Salmonella was also assessed after subsequent brewing using dried inoculated teas. A Salmonella enterica serovar cocktail was inoculated onto different dried tea leaves or flowers to give starting populations of approximately 10 log CFU/g. The inoculum was allowed to dry (at ambient temperature for 24 h) onto the dried leaves or flowers prior to storage under 25 and 35 °C at low (90% RH) humidity levels. Under the four storage conditions tested, survival followed the order 25 °C with low RH > 35 °C with low RH > 25 °C with high RH > 35 °C with high RH. Salmonella losses at 25 °C with low RH occurred primarily during drying, after which populations showed little decline over 6 months. In contrast, Salmonella decreased below detection after 45 days at 35 °C and high RH in all teas tested. The thermal resistance of Salmonella was assessed at 55 °C immediately after inoculation of tea leaves or flowers, after drying (24 h) onto tea leaves or flowers, and after 28 days of storage at 25 °C with low RH. All conditions resulted in similar D-values (2.78 ± 0.12, 3.04 ± 0.07, and 2.78 ± 0.56, at 0 h, 24 h, and 28 days, respectively), indicating thermal resistance of Salmonella in brewed tea did not change after desiccation and 28 days of storage. In addition, all brewed teas tested supported the growth of Salmonella. If Salmonella survives after storage, it may also survive and grow after a home brewing process.