In Vitro and In Vivo Evaluation of the Antifungal Activity of APX001A/APX001 against Candida auris.

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 MIC50 and MIC90 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.

Biofilms and beyond: expanding echinocandin utility.

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-ß-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-ß-d-glucan synthesis inhibition in these areas of emerging interest.

Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model.

Background: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. Objectives: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. Methods: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 107C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day. Results: Rezafungin had significantly lower average log10 cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log10 cfu/g of tissue compared with micafungin-treated mice on day 10. Conclusions: Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.

Antimicrobial Activity of Silver Containing Crosslinked Poly(Acrylic Acid) Fibers.

: Bacterial and fungal pathogens have caused serious problems to the human health. This is particularly true for untreatable infectious diseases and clinical situations where there is no reliable treatment for infected patients. To increase the antimicrobial activity of materials, we introduce silver nanoparticle (NP) patches in which the NPs are incorporated to the surface of smooth and uniform poly(acrylic acid) (PAA) nanofibers. The PAA nanofibers were thermally crosslinked with ethylene glycol via heat treatment through a mild method. The characterization of the resulting PAA-silver NP patches was done using scanning electron microscopy (SEM), UV spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). To demonstrate the antimicrobial activity of PAA, we incorporated the patches containing the silver NPs into strains of fungi such as Candida albicans (C. albican) and bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA). The PAA-silver fibers achieved zones of inhibition against C. albicans and MRSA indicating their antimicrobial activity against both fungi and bacteria. We conclude that silver NP patches exhibited multiple inhibitory actions for the interruption and blockage of activity fungal and bacterial strains, which has the potential as an antimicrobial agent in infectious diseases. Moreover, the proposed material has the potential to be used in antimicrobial textile fabrics, food packaging films, and wound dressings.

Relative Resistance of the Emerging Fungal Pathogen Candida auris and Other Candida Species to Killing by Ultraviolet Light.

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.

Effectiveness of Disinfectants Against Candida auris and Other Candida Species.

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.

Survival of Salmonella during Drying of Fresh Ginger Root (Zingiber officinale) and Storage of Ground Ginger.

The survival of Salmonella on fresh ginger root (Zingiber officinale) during drying was examined using both a laboratory oven at 51 and 60°C with two different fan settings and a small commercially available food dehydrator. The survival of Salmonella in ground ginger stored at 25 and 37°C at 33% (low) and 97% (high) relative humidity (RH) was also examined. To inoculate ginger, a four-serovar cocktail of Salmonella was collected by harvesting agar lawn cells. For drying experiments, ginger slices (1 ± 0.5 mm thickness) were surface inoculated at a starting level of approximately 9 log CFU/g. Higher temperature (60°C) coupled with a slow fan speed (nonstringent condition) to promote a slower reduction in the water activity (aw) of the ginger resulted in a 3- to 4-log reduction in Salmonella populations in the first 4 to 6 h with an additional 2- to 3-log reduction by 24 h. Higher temperature with a higher fan speed (stringent condition) resulted in significantly less destruction of Salmonella throughout the 24-h period (P < 0.001). Survival appeared related to the rate of reduction in the aw. The aw also influenced Salmonella survival during storage of ground ginger. During storage at 97% RH, the maximum aw values were 0.85 at 25°C and 0.87 at 37°C; Salmonella was no longer detected after 25 and 5 days of storage, respectively, under these conditions. At 33% RH, the aw stabilized to approximately 0.35 at 25°C and 0.31 at 37°C. Salmonella levels remained relatively constant throughout the 365-day and 170-day storage periods for the respective temperatures. These results indicate a relationship between temperature and aw and the survival of Salmonella during both drying and storage of ginger.

Survival of Salmonella on chamomile, peppermint, and green tea during storage and subsequent survival or growth following tea brewing.

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 (<30% relative humidity [RH]) and high (>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.