Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

We describe a case of tinea genitalis in an immunocompetent woman in Pennsylvania, USA. Infection was caused by Trichophyton indotineae potentially acquired through sexual contact. The fungus was resistant to terbinafine (first-line antifungal) but improved with itraconazole. Clinicians should be aware of T. indotineae as a potential cause of antifungal-resistant genital lesions.

The Response of the Urinary Microbiome to Botox.

INTRODUCTION AND HYPOTHESIS: Our objective was to evaluate if botox alters the urinary microbiome of patients with overactive bladder and whether this alteration is predictive of treatment response. METHODS: This multicenter prospective cohort study included 18-89-year-old patients undergoing treatment for overactive bladder with 100 units of botox. Urine samples were collected by straight catheterization on the day of the procedure (S1) and again 4 weeks later (S2). Participants completed the Patient Global Impression of Improvement form at their second visit for dichotomization into responders and nonresponders. The microbiome was sequenced using 16s rRNA sequencing. Wilcoxon signed rank and Wilcoxon rank sum were used to compare the microbiome, whereas chi-square, Wilcoxon rank sum, and the independent t-test were utilized for clinical data. RESULTS: Sixty-eight participants were included in the analysis. The mean relative abundance and prevalence of Beauveria bassiana, Xerocomus chrysenteron, Crinipellis zonata, and Micrococcus luteus were all found to increase between S1 and S2 in responders; whereas in nonresponders the mean relative abundance and prevalence of Pseudomonas fragi were found to decrease. The MRA and prevalence of Weissella cibaria, Acinetobacter johnsonii, and Acinetobacter schindleri were found to be greater in responders than nonresponders at the time of S1. Significant UM differences in the S1 of patients who did (n = 5) and did not go on to develop a post-treatment UTI were noted. CONCLUSIONS: Longitudinal urobiome differences may exist between patients who do and do not respond to botox.

Skin and gut microbial associations with squamous cell carcinoma in solid organ transplant recipients.

Solid organ transplant recipients (SOTRs) are burdened with a significantly higher risk of squamous cell carcinoma (SCC) compared to the general population. Accumulating evidence suggests the potential influence of microbial dysbiosis on transplant outcomes. Based on these observations, we sought to identify differences in the cutaneous and gut microbiomes of SOTRs with and without a history of SCC. This case-control study collected and analyzed non-lesional skin and fecal samples of 20 SOTRs > 18 years old with either ≥ 4 diagnoses of SCC since most recent transplant (n = 10) or 0 diagnoses of SCC (n = 10). The skin and gut microbiomes were investigated with Next-Generation Sequencing, and analysis of variance (ANOVA) followed by Tukey pairwise comparison procedure was used to test for differences in taxonomic relative abundances and microbial diversity indices between the two cohorts. Analyses of the skin microbiome showed increased bacterial and reduced fungal diversity in SOTRs with a history of SCC compared to SOTRs without a history of SCC (bacterial median Shannon diversity index (SDI) = 3.636 and 3.154, p < 0.05; fungal SDI = 4.474 and 6.174, p < 0.05, respectively). Analyses of the gut microbiome showed reduced bacterial and fungal diversity in the SCC history cohort compared to the SCC history-negative cohort (bacterial SDI = 2.620 and 3.300, p < 0.05; fungal SDI = 3.490 and 3.812, p < 0.05, respectively). The results of this pilot study thus show a trend toward the bacterial and fungal communities of the gut and skin being distinct in SOTRs with a history of SCC compared to SOTRs without a history of SCC. It furthermore demonstrates the potential for microbial markers to be used in the prognostication of squamous cell carcinoma risk in solid organ transplant recipients.

Antifungal Activity of Efinaconazole Compared to Fluconazole, Itraconazole, and Terbinafine against Terbinafine- and Itraconazole-Resistant and -Susceptible Clinical Isolates of Dermatophytes, Candida, and Mold.

BACKGROUND: Recently, an increasing number of resistant-to-terbinafine dermatophytosis cases have been reported. Thus, identifying an alternative antifungal agent that possesses a broad-spectrum activity, including against resistant strains, is needed. METHODS: In this study, we compared the antifungal activity of efinaconazole to fluconazole, itraconazole, and terbinafine against clinical isolates of dermatophyte, Candida, and molds using in vitro assays. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of each antifungal was quantified and compared. Both susceptible and resistant clinical isolates of Trichophyton mentagrophytes (n=16), T. rubrum (n=43), T. tonsurans (n=18), T. violaceum (n=4), Candida albicans (n=55), C. auris (n=30), Fusarium sp., Scedosporium sp., and Scopulariopsis sp. (n=15 for each) were tested. RESULTS: Our data shows that efinaconazole was the most active antifungal, compared to the other agents tested, against dermatophytes with MIC50 and MIC90 (Concentration that inhibited 50% and 90% of strains tested, respectively) values of 0.002 and 0.03 µg/ml, respectively. Fluconazole, itraconazole and terbinafine showed MIC50 and MIC90 values of 1 and 8 µg/ml, 0.03 and 0.25 µg/ml, and 0.031 and 16 µg/ml, respectively. Against Candida isolates, efinaconazole MIC50 and MIC90 values were 0.016 and 0.25 µg/ml, respectively, whereas fluconazole, itraconazole and terbinafine had MIC50 and the MIC90 values of 1 and 16 µg/ml, 0.25 and 0.5 µg/ml, and 2 and 8 µg/ml, respectively. Against various mold species, efinaconazole MIC values ranged from 0.016 and 2 µg/ml, compared to 0.5 to greater than 64 µg/ml for the comparators. CONCLUSIONS: efinaconazole showed superior potent activity against a broad panel of susceptible and resistant dermatophyte, Candida, and mold isolates.

Modulating the Microbiome for Crohn's Disease Treatment.

The central role of the gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial interkingdom interactions between bacterial (the bacteriome) and fungal (the mycobiome) communities of the gut have become a prominent focus for development of potential therapeutic approaches. In addition to polymicrobial interactions, the complex gut ecosystem also mediates interactions between the host and the microbiota. These interactions are complex and bidirectional; microbiota composition can be influenced by host immune response, disease-specific therapeutics, antimicrobial drugs, and overall ecosystems. However, the gut microbiota also influences host immune response to a drug or therapy by potentially transforming the drug's structure and altering bioavailability, activity, or toxicity. This is especially true in cases where the gut microbiota has produced a biofilm. The negative ramifications of biofilm formation include alteration of gut permeability, enhanced antimicrobial resistance, and alteration of host immune response effectiveness. Natural modulation of the gut microbiota, using probiotic and prebiotic approaches, may also be used to affect the host microbiome, a type of "natural" modulation of the host microbiota composition. In this review, we discuss potential bidirectional interactions between microbes and host, and we describe the changes in gut microbiota induced by probiotic and prebiotic approaches as well as their potential clinical consequences, including biofilm formation. We outline a systematic approach to designing probiotics capable of altering the host microbiota in disease states, using Crohn's disease as a model chronic disease. Understanding how the effective changes in the microbiome may enhance treatment efficacy may unlock the possibility of modulating the gut microbiome to improve treatment using a natural approach.

Dermatophyte Infections Worldwide: Increase in Incidence and Associated Antifungal Resistance.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Cutaneous dysbiosis may amplify barrier dysfunction in patients with atopic dermatitis.

Atopic dermatitis (AD) is associated with cutaneous dysbiosis, barrier defects, and immune dysregulation, but the interplay between these factors needs further study. Early-onset barrier dysfunction may facilitate an innate immune response to commensal organisms and, consequently, the development of allergic sensitization. We aimed to compare the cutaneous microbiome in patients with active dermatitis with and without a history of childhood flexural dermatitis (atopic dermatitis). Next-gen Ion-Torrent deep-sequencing identified AD-associated changes in the skin bacterial microbiome ("bacteriome") and fungal microbiome ("mycobiome") of affected skin in swabs from areas of skin affected by dermatitis. Data were analyzed for diversity, abundance, and inter-kingdom correlations. Microbial interactions were assessed in biofilms using metabolic activity (XTT) assay and scanning electron microscopy (SEM), while host-pathogen interactions were determined in cultured primary keratinocytes exposed to biofilms. Increased richness and abundance of Staphylococcus, Lactococcus, and Alternaria were found in atopics. Staphylococcus and Alternaria formed robust mixed-species biofilms (based on XTT and SEM) that were resistant to antifungals/antimicrobials. Furthermore, their biofilm supernatant was capable of influencing keratinocytes biology (pro-inflammatory cytokines and structural proteins), suggesting an additive effect on AD-associated host response. In conclusion, microbial inter-kingdom and host-microbiome interactions may play a critical role in the modulation of atopic dermatitis to a greater extent than in non-atopic adults with allergic contact dermatitis.

Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections.

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections.

Multicenter Collaborative Study of the Interaction of Antifungal Combinations against Candida Spp. by Loewe Additivity and Bliss Independence-Based Response Surface Analysis.

Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against Candida albicans, C. parapsilosis, and C. glabrata. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5−4, indicating no significant pharmacodynamic interactions for all of the strain−combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ2 646, p < 0.0001). Using a narrower additivity range of 1−2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all Candida strains except C. glabrata. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all Candida strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against C. albicans. The AZO+AZO combination was additive for all strains except for a C. parapsilosis strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all Candida strains except C. glabrata for which they were additive; no antagonism was found.

Sarecycline Demonstrates Clinical Effectiveness against Staphylococcal Infections and Inflammatory Dermatoses: Evidence for Improving Antibiotic Stewardship in Dermatology.

Tetracycline class antibiotics are widely used for multiple skin diseases, including acne vulgaris, acne rosacea, cutaneous infections, inflammatory dermatoses, and autoimmune blistering disorders. Concerns about antibiotic resistance and protecting the human/host microbiome beg the question whether broad-spectrum tetracyclines such as doxycycline and minocycline should be prescribed at such a high rate by dermatologists when a narrow-spectrum tetracycline derivative, sarecycline, exists. We evaluated the clinical effectiveness of oral sarecycline against cutaneous staphylococcal infections, eyelid stye, and mucous membrane pemphigoid to determine whether sarecycline is a viable option for clinicians to practice improved antibiotic stewardship. We observed significant improvement in staphylococcal infections and inflammatory dermatoses with courses of oral sarecycline as short as 9 days, with no reported adverse events. These clinical findings are consistent with in vitro microbiological data and anti-inflammatory properties of sarecycline. Our data provides a strong rationale for clinicians to use narrow-spectrum sarecycline rather than broad-spectrum tetracyclines as a first-line agent in treating staphylococcal skin infections and inflammatory skin diseases for which tetracyclines are currently commonly employed. Such advancement in the practice paradigm in dermatology will enhance antibiotic stewardship, reduce risk of antibiotic resistance, protect the human microbiome, and provide patients with precision medicine care.

The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs).

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities.

In Vivo Skin Colonization and Decolonization Models for Candida auris.

Candida auris infections present a critical problem to the healthcare system in many parts of the world. This yeast clinically manifests as a disseminated candidiasis which can be life-threating for susceptible individuals, as well as cutaneous and wound infections. Moreover, C. auris can colonize the skin and act as a nidus of infection. Importantly, this emerging yeast unlike other Candida spp. has demonstrated multidrug resistance; thus its eradication can be challenging. Animal models are important to gain insight into the pathogenesis of this infection, as well as play a significant role in drug development. In this chapter, we describe two C. auris animal models: a cutaneous infection guinea pig model and a skin decolonization mouse model.

An Immunocompromised Mouse Model of Candida auris Systemic Infection.

With the recent emergence of multidrug-resistant Candida auris, there is an urgent need for new antifungal compounds with novel pharmacodynamic and pharmacokinetic properties that can treat systemic fungal infections caused by this emerging yeast. Historically, testing the efficacy of treatment for disseminated candidiasis was accomplished using a diverse array of in vivo animal models, including mice which offer an advantage both in their similarities to humans and their lower cost of maintenance. However, in order to create effective in vivo models for testing new antifungal compounds designed to treat systemic infections, it is important that these models also mimic several of the relevant predisposing conditions that can lead to disseminated candidiasis. Here, we describe an immunocompromised mouse model of hematogenously disseminated C. auris infection, which may have utility to test the efficacy of candidate antifungal compounds.

Diagnosing Onychomycosis: What's New?

An overview of the long-established methods of diagnosing onychomycosis (potassium hydroxide testing, fungal culture, and histopathological examination) is provided followed by an outline of other diagnostic methods currently in use or under development. These methods generally use one of two diagnostic techniques: visual identification of infection (fungal elements or onychomycosis signs) or organism identification (typing of fungal genus/species). Visual diagnosis (dermoscopy, optical coherence tomography, confocal microscopy, UV fluorescence excitation) provides clinical evidence of infection, but may be limited by lack of organism information when treatment decisions are needed. The organism identification methods (lateral flow techniques, polymerase chain reaction, MALDI-TOF mass spectroscopy and Raman spectroscopy) seek to provide faster and more reliable identification than standard fungal culture methods. Additionally, artificial intelligence methods are being applied to assist with visual identification, with good success. Despite being considered the 'gold standard' for diagnosis, clinicians are generally well aware that the established methods have many limitations for diagnosis. The new techniques seek to augment established methods, but also have advantages and disadvantages relative to their diagnostic use. It remains to be seen which of the newer methods will become more widely used for diagnosis of onychomycosis. Clinicians need to be aware of the limitations of diagnostic utility calculations as well, and look beyond the numbers to assess which techniques will provide the best options for patient assessment and management.

Sarecycline Demonstrated Reduced Activity Compared to Minocycline against Microbial Species Representing Human Gastrointestinal Microbiota.

Prolonged use of broad-spectrum tetracycline antibiotics such as minocycline and doxycycline may significantly alter the gut and skin microbiome leading to dysbiosis. Sarecycline, a narrow-spectrum tetracycline-class antibiotic used for acne treatment, is hypothesized to have minimal impact on the gastrointestinal tract microbiota. We evaluated the effect of sarecycline compared to minocycline against a panel of microorganisms that reflect the diversity of the gut microbiome using in vitro minimum inhibitory concentration (MIC) and time-kill kinetic assays. Compared to minocycline, sarecycline showed less antimicrobial activity indicated by higher MIC against 10 of 12 isolates from the Bacteroidetes phylum, three out of four isolates from Actinobacteria phylum, and five of seven isolates from the Firmicutes phylum, with significantly higher MIC values against Propionibacterium freudenreichii (≥3 dilutions). In time-kill assays, sarecycline demonstrated significantly less activity against Escherichia coli compared to minocycline at all time-points (p < 0.05). Moreover, sarecycline was significantly less effective in inhibiting Candida tropicalis compared to minocycline following 20- and 22-h exposure. Furthermore, sarecycline showed significantly less activity against Lactobacillus paracasei (recently renamed as Lacticaseibacillus paracasei subsp. paracasei) (p = 0.002) and Bifidobacterium adolescentis at 48 h (p = 0.042), when compared to minocycline. Overall, sarecycline demonstrated reduced antimicrobial activity against 79% of the tested gut microorganisms, suggesting that it is less disruptive to gut microbiota compared with minocycline. Further in vivo testing is warranted.

Gut-derived bacterial toxins impair memory CD4+ T cell mitochondrial function in HIV-1 infection.

People living with HIV (PLWH) who are immune nonresponders (INRs) are at greater risk of comorbidity and mortality than are immune responders (IRs) who restore their CD4+ T cell count after antiretroviral therapy (ART). INRs have low CD4+ T cell counts (<350 c/µL), heightened systemic inflammation, and increased CD4+ T cell cycling (Ki67+). Here, we report the findings that memory CD4+ T cells and plasma samples of INRs from several cohorts are enriched in gut-derived bacterial solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) that both negatively correlated with CD4+ T cell counts. In vitro PCS or IS blocked CD4+ T cell proliferation, induced apoptosis, and diminished the expression of mitochondrial proteins. Electron microscopy imaging revealed perturbations of mitochondrial networks similar to those found in INRs following incubation of healthy memory CD4+ T cells with PCS. Using bacterial 16S rDNA, INR stool samples were found enriched in proteolytic bacterial genera that metabolize tyrosine and phenylalanine to produce PCS. We propose that toxic solutes from the gut bacterial flora may impair CD4+ T cell recovery during ART and may contribute to CD4+ T cell lymphopenia characteristic of INRs.

Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

BACKGROUND: Current treatment of vulvovaginal candidiasis (VVC) is largely limited to azole therapy. Ibrexafungerp is a first-in-class triterpenoid antifungal with broad-spectrum anti-Candida fungicidal activity. The objective of this study was to evaluate the efficacy and safety of ibrexafungerp compared with placebo in patients with acute VVC. METHODS: Patients were randomly assigned 2:1 to receive ibrexafungerp (300 mg twice for 1 day) or placebo. The primary endpoint was the percentage of patients with a clinical cure (complete resolution of vulvovaginal signs and symptoms [VSS] = 0) at test-of-cure (day 11 ± 3). Secondary endpoints included the percentage of patients with mycological eradication, overall success (clinical cure and mycological eradication), clinical improvement (VSS ≤ 1) at test-of-cure, and symptom resolution at follow-up (day 25 ± 4). RESULTS: Patients receiving ibrexafungerp had significantly higher rates of clinical cure (50.5% [95/188] vs 28.6% [28/98]; P = .001), mycological eradication (49.5% [93/188] vs 19.4% [19/98]; P < .001), and overall success (36.0% [64/178] vs 12.6% [12/95]; P < .001) compared with placebo. Symptom resolution was sustained and further increased with ibrexafungerp compared with placebo (59.6% [112/188] vs 44.9% [44/98]; P = .009) at follow-up. Post hoc analysis showed similar rates of clinical cure and clinical improvement at test-of-cure for Black patients (54.8% [40/73] and 63.4% [47/73], respectively) and patients with a body mass index >35 (54.5% [24/44] and 68.2% [30/44], respectively) compared with overall rates. Ibrexafungerp was well tolerated. Adverse events were primarily gastrointestinal and mild in severity. CONCLUSIONS: Ibrexafungerp provides a promising safe and efficacious oral treatment that mechanistically differs from current azole treatment options for acute VVC.

Evaluation of Microbiome Alterations Following Consumption of BIOHM, a Novel Probiotic.

Gastrointestinal microbiome dysbiosis may result in harmful effects on the host, including those caused by inflammatory bowel diseases (IBD). The novel probiotic BIOHM, consisting of Bifidobacterium breve, Saccharomyces boulardii, Lactobacillus acidophilus, L. rhamnosus, and amylase, was developed to rebalance the bacterial-fungal gut microbiome, with the goal of reducing inflammation and maintaining a healthy gut population. To test the effect of BIOHM on human subjects, we enrolled a cohort of 49 volunteers in collaboration with the Fermentation Festival group (Santa Barbara, CA, USA). The profiles of gut bacterial and fungal communities were assessed via stool samples collected at baseline and following 4 weeks of once-a-day BIOHM consumption. Mycobiome analysis following probiotic consumption revealed an increase in Ascomycota levels in enrolled individuals and a reduction in Zygomycota levels (p value < 0.01). No statistically significant difference in Basidiomycota was detected between pre- and post-BIOHM samples and control abundance profiles (p > 0.05). BIOHM consumption led to a significant reduction in the abundance of Candida genus in tested subjects (p value < 0.013), while the abundance of C. albicans also trended lower than before BIOHM use, albeit not reaching statistical significance. A reduction in the abundance of Firmicutes at the phylum level was observed following BIOHM use, which approached levels reported for control individuals reported in the Human Microbiome Project data. The preliminary results from this clinical study suggest that BIOHM is capable of significantly rebalancing the bacteriome and mycobiome in the gut of healthy individuals, suggesting that further trials examining the utility of the BIOHM probiotic in individuals with gastrointestinal symptoms, where dysbiosis is considered a source driving pathogenesis, are warranted.

A Microbiome-Driven Approach to Combating Depression During the COVID-19 Pandemic.

The significant stressors brought about and exacerbated by COVID-19 are associated with startling surges in mental health illnesses, specifically those related to depressive disorders. Given the huge impact of depression on society, and an incomplete understanding of impactful therapeutics, we have examined the current literature surrounding the microbiome and gut-brain axis to advance a potential complementary approach to address depression and depressive disorders that have increased during the COVID-19 pandemic. While we understand that the impact of the human gut microbiome on emotional health is a newly emerging field and more research needs to be conducted, the current evidence is extremely promising and suggests at least part of the answer to understanding depression in more depth may lie within the microbiome. As a result of these findings, we propose that a microbiome-based holistic approach, which involves carefully annotating the microbiome and potential modification through diet, probiotics, and lifestyle changes, may address depression. This paper's primary purpose is to shed light on the link between the gut microbiome and depression, including the gut-brain axis and propose a holistic approach to microbiome modification, with the ultimate goal of assisting individuals to manage their battle with depression through diet, probiotics, and lifestyle changes, in addition to offering a semblance of hope during these challenging times.

Efficacy of Voriconazole, Isavuconazole, Fluconazole, and Anidulafungin in the Treatment of Emerging Candida auris Using an Immunocompromised Murine Model of Disseminated Candidiasis.

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. MICs for anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 µg/ml, respectively. Significant in vivo efficacy was observed in the anidulafungin- and voriconazole-treated groups in survival and reduction in kidney tissue fungal burden compared to that in the untreated group (P values of <0.001 and 0.044, respectively). Our data showed that anidulafungin and voriconazole had comparable efficacies against C. auris, whereas isavuconazole did not show significant in vivo activity.