scholarly journals A Novel Transdermal Application for Clearing Skin Colonization by Candida auris

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
M. Ghannoum ◽  
J. Herrada ◽  
T. S. McCormick ◽  
L. Long
Keyword(s):  
Hospitalized Patients ◽  
Novel Agents ◽  
Control Groups ◽  
Candida Auris ◽  
Content Type ◽  
Fungal Burden ◽  
Transdermal Application ◽  
Colonization Model ◽  
Skin Colonization

ABSTRACT Candida auris has demonstrated the ability to colonize the skin of hospitalized patients, possibly contributing to nosocomial spread. The objective of this study was to determine whether two novel transdermal agents could clear skin colonization established by C. auris. A murine skin colonization model was first optimized and then used to test fungal burden reduction following treatment with 1% terbinafine or 1% clotrimazole in a proprietary Advanced Penetration Technology formulation (APT). Both treatments significantly reduced fungal burden compared to that in control groups. These novel agents show promise as a topical means of preventing skin colonization by C. auris.

scholarly journals Efficacy of Ibrexafungerp (SCY-078) against Candida auris in an In Vivo Guinea Pig Cutaneous Infection Model

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
M. Ghannoum ◽  
N. Isham ◽  
D. Angulo ◽  
K. Borroto-Esoda ◽  
S. Barat ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Skin Infection ◽  
Hospitalized Patients ◽  
Infection Model ◽  
Candida Auris ◽  
Content Type ◽  
Fungal Burden ◽  
Clinical Appearance ◽  
Skin Colonization

ABSTRACT Candida auris has been shown to have a high risk of skin colonization in hospitalized patients, possibly contributing to nosocomial spread. In a guinea pig skin model, animals were evaluated for clinical appearance, tissue fungal burden, histology, and pharmacokinetics. Oral dosing with 10 mg/kg ibrexafungerp (IBX) reduced the severity of lesions and significantly reduced the C. auris fungal burden in infected animals compared with untreated controls. This indicates promise for use of IBX in controlling skin infection and colonization of hospitalized patients.

scholarly journals The Fungal Cyp51-Specific Inhibitor VT-1598 DemonstratesIn VitroandIn VivoActivity againstCandida auris

2018 ◽  
Vol 63 (3) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Shawn R. Lockhart ◽  
Laura K. Najvar ◽  
Elizabeth L. Berkow ◽  
Rosie Jaramillo ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Candida Auris ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden ◽  
Invasive Infections ◽  
Trough Concentrations ◽  
Dose Dependent

ABSTRACTCandida aurisis an emerging pathogen associated with significant mortality and often multidrug resistance. VT-1598, a tetrazole-based fungal CYP51-specific inhibitor, was evaluatedin vitroandin vivoagainstC. auris. Susceptibility testing was performed against 100 clinical isolates ofC. aurisby broth microdilution. Neutropenic mice were infected intravenously withC. auris, and treatment began 24 h postinoculation with a vehicle control, oral VT-1598 (5, 15, and 50 mg/kg of body weight once daily), oral fluconazole (20 mg/kg once daily), or intraperitoneal caspofungin (10 mg/kg once daily), which continued for 7 days. Fungal burden was assessed in the kidneys and brains on day 8 in the fungal burden arm and on the days the mice succumbed to infection or on day 21 in the survival arm. VT-1598 plasma trough concentrations were also assessed on day 8. VT-1598 demonstratedin vitroactivity againstC. auris, with a mode MIC of 0.25 μg/ml and MICs ranging from 0.03 to 8 μg/ml. Treatment with VT-1598 resulted in significant and dose-dependent improvements in survival (median survival, 15 and >21 days for VT-1598 at 15 and 50 mg/kg, respectively) and reductions in kidney and brain fungal burden (reductions of 1.88 to 3.61 log10CFU/g) compared to the control (5 days). The reductions in fungal burden correlated with plasma trough concentrations. Treatment with caspofungin, but not fluconazole, also resulted in significant improvements in survival and reductions in fungal burden compared to those with the control. These results suggest that VT-1598 may be a future option for the treatment of invasive infections caused byC. auris.

scholarly journals The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Rosie Jaramillo ◽  
Marcos Olivo ◽  
Hoja Patterson ◽  
...  
Keyword(s):  
The Novel ◽  
Candida Auris ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden

ABSTRACT The in vitro and in vivo activity of the arylamidine T-2307 against Candida auris was evaluated. T-2307 demonstrated in vitro activity (MIC ranges ≤ 0.008 to 0.015 μg/ml at 50% inhibition; 0.125 to >4 μg/ml at 100% inhibition). Treatment with T-2307 (3 mg/kg subcutaneous [SC] once daily) also significantly improved survival (70% at 21 days postinfection) and reduced kidney fungal burden (5.06 log10 CFU/g) compared to control (0% survival and 7.09 log10 CFU/g) (P < 0.01).

scholarly journals Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of Candida auris Invasive Candidiasis

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Karen J. Shaw ◽  
Rosie Jaramillo ◽  
Hoja Patterson ◽  
...  
Keyword(s):  
Murine Model ◽  
Invasive Candidiasis ◽  
Pathogenic Fungi ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden ◽  
Fluconazole Resistant

ABSTRACT The emerging pathogenic yeast Candida auris is associated with antifungal resistance and high mortality. The novel antifungal agent manogepix (APX001A) inhibits glycosylphosphatidylinositol-anchored protein maturation and has demonstrated activity against numerous pathogenic fungi, including C. auris. Our objective was to evaluate the in vivo efficacy of fosmanogepix, the N-phosphonooxymethyl prodrug (APX001), following delayed initiation of therapy in a murine model of C. auris invasive candidiasis. Neutropenic mice were intravenously infected with a fluconazole-resistant clinical isolate of C. auris. Twenty-four hours postinoculation, treatment began with vehicle control, fosmanogepix (104 and 130 mg/kg of body weight by intraperitoneal injection three times daily, or intraperitoneal 260 mg/kg twice daily), fluconazole (20 mg/kg by oral gavage once daily), or caspofungin (intraperitoneal 10 mg/kg once daily) and continued for 7 days. Fungal burden was assessed via colony count in the kidneys and brains on day 8 in the fungal burden arm and on day 21 as the mice became moribund in the survival arm. Significant improvements in survival were observed in each group administered fosmanogepix and caspofungin. Similarly, reductions in fungal burden were also observed in both the kidneys and brains of mice treated with the highest dose of fosmanogepix in the fungal burden arm and in each fosmanogepix group and with caspofungin in the survival arm. In contrast, no improvements in survival or reductions in fungal burden were observed in mice treated with fluconazole. These results demonstrate that fosmanogepix is effective in vivo against fluconazole-resistant C. auris even when therapy is delayed.

scholarly journals Candida auris: an Emerging Fungal Pathogen

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
Emily S. Spivak ◽  
Kimberly E. Hanson
Keyword(s):  
Health Care ◽  
Fungal Pathogen ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Environmental Persistence ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Hospital Infection Control ◽  
Skin Colonization

ABSTRACT Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. Recent reports highlight ongoing challenges due to organism misidentification, high rates of antifungal drug resistance, and significant patient mortality. The predilection for transmission within and between health care facilities possibly promoted by virulence factors that facilitate skin colonization and environmental persistence is unique among Candida species. This minireview details the global emergence of C. auris and discusses issues relevant to clinical microbiology laboratories, hospital infection control, and antimicrobial stewardship efforts.

scholarly journals Metagenomic Sequencing for Direct Identification of Candida auris Colonization

mSphere ◽  
2021 ◽  
Author(s):  
Teresa R. O’Meara
Keyword(s):  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Skin Microbiome ◽  
Metagenomic Sequencing ◽  
Nursing Facilities ◽  
Candida Auris ◽  
Direct Identification ◽  
Skilled Nursing ◽  
Content Type ◽  
Skin Colonization

Candida auris is an emerging multidrug-resistant yeast that is associated with skin colonization and deadly bloodstream infections, especially in ventilator skilled nursing facilities. An ongoing question is how this organism colonizes the skin of these patients and whether the skin microbiome provides a measure of colonization resistance against C. auris .

scholarly journals The Novel Arylamidine T-2307 MaintainsIn VitroandIn VivoActivity against Echinocandin-Resistant Candida albicans

2014 ◽  
Vol 59 (2) ◽  
pp. 1341-1343 ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Annette W. Fothergill ◽  
Rosie Bocanegra ◽  
Marcos Olivo ◽  
...  
Keyword(s):  
Body Weight ◽  
Candida Albicans ◽  
Invasive Candidiasis ◽  
Placebo Control ◽  
The Novel ◽  
Content Type ◽  
Fungal Burden ◽  
Potential Use

ABSTRACTWe evaluated thein vitroandin vivoactivities of the investigational arylamidine T-2307 against echinocandin-resistantCandida albicans. T-2307 demonstrated potentin vitroactivity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistantC. albicansinfections.

The effect of dexamethasone on the rate of formation of cerebrospinal fluid in the monkey

1974 ◽  
Vol 41 (5) ◽  
pp. 550-554 ◽  
Author(s):  
Albert N. Martins ◽  
Archimedes Ramirez ◽  
Lewis S. Solomon ◽  
G. Michael Wiese
Keyword(s):  
Formation Rate ◽  
Therapeutic Benefit ◽  
Intravenous Dose ◽  
Control Groups ◽  
Perfusion Technique ◽  
Content Type ◽  
Ventriculocisternal Perfusion ◽  
And Control ◽  
Csf Formation Rate ◽  
Fine Print

✓ The standard ventriculocisternal perfusion technique was used to determine what effect a single large intravenous dose of dexamethasone would have on CSF formation rate in the rhesus monkey over a 4-hour period. Three monkeys received 0.15 mg/kg, four received 0.4 mg/kg and five served as the untreated controls. With time, CSF formation rates decreased in both treated and control groups. The magnitude of the decrease in the treated and untreated controls did not differ significantly. We conclude that the therapeutic benefit of dexamethasone for intracranial spatial decompensation derives from a mechanism of action that leaves the rate of CSF formation unchanged.

scholarly journals In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris

2021 ◽  
Author(s):  
Janet Herrada ◽  
Ahmed Gamal ◽  
Lisa Long ◽  
Sonia P. Sanchez ◽  
Thomas S. McCormick ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Amphotericin B ◽  
Kidney Tissue ◽  
Treated Group ◽  
Untreated Group ◽  
Candida Auris ◽  
Fungal Burden ◽  
In Vivo Antifungal Activity

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/mL, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg -treated group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data shows that AmBisome shows significant antifungal activity against C. auris in vitro as well as in vivo.

scholarly journals Complete Genome Sequence of Klebsiella aerogenes Myophage Metamorpho

2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Kyra E. Groover ◽  
Kameron Garza ◽  
James Clark ◽  
Isla Hernandez ◽  
Jason J. Gill ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Opportunistic Pathogen ◽  
Hospitalized Patients ◽  
Klebsiella Aerogenes ◽  
Content Type

ABSTRACT The bacterium Klebsiella aerogenes is an opportunistic pathogen that often infects hospitalized patients and those who are immunocompromised. K. aerogenes in some cases can become resistant to antibiotic treatment. Being a potential therapeutic, Metamorpho is a T4-like myophage targeting K. aerogenes.

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