Mahmoud A Ghannoum

• M.SC., PH.D., M.B.A
• Managing Director at Case Western Reserve University

Background: Topical treatment of toenail onychomycosis may be preferred for patients for whom systemic adverse events, drug-drug interactions, and contraindications associated with oral antifungals are of concern. Three topical antifungals have been approved by the US Food and Drug Administration (FDA) for the treatment of toenail onychomycosis: ci...

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of postbiotics (cell wall componen...

Introduction: Acne guidelines recommend the addition of benzoyl peroxide (BPO) to antibiotics to reduce resistance in Cutibacterium acnes (C. acnes). Pairing the antibiotic/BPO combination with a retinoid, such as adapalene, may further increase treatment efficacy, although research on adapalene’s antibacterial activity is limited. To determine if...

The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses, leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of a recently developed probiotic + amylase blend in the SAMP1...

The interaction between gut-residing microorganisms plays a critical role in the pathogenesis of Crohn’s disease (CD), where microbiome dysregulation can alter immune responses leading to unresolved local inflammation. The aim of this study is to analyze the immunomodulatory properties of our recently developed probiotic+amylase blend in the SAMP1/...

Autism Spectrum Disorder (ASD) is a multifactorial disorder involving genetic and environmental factors leading to pathophysiologic symptoms and comorbidities including neurodevelopmental disorders, anxiety, immune dysregulation, and gastrointestinal (GI) abnormalities. Abnormal intestinal permeability has been reported among ASD patients and it is...

Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosi...

The present study was performed to determine if ingesting a blend of probiotics plus amylase would alter the abundance and diversity of gut microbiota in subjects consuming the blend over a 6-week period. 16S and ITS ribosomal RNA (rRNA) sequencing was performed on fecal samples provided by subjects who participated in a clinical study where they c...

Unlabelled: Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathologic factors on chemotherapy response, the role of the gut microbiome (GM) in bladder...

Candida (C.) infections represent a serious health risk for people affected by inflammatory bowel disease. An important fungal virulence factor is the capacity of the fungus to form biofilms on the colonized surface of the host. This research study aimed to determine the effect of a C. tropicalis and C. albicans co-infection on dextran sodium sulfa...

Background: Onychomycosis is typically caused by dermatophytes of the species Trichophyton. Topical antifungals must penetrate the nail to reach the infection, though this can be inhibited by keratin binding within the nail. These in vitro experiments compared penetration of commercially available topical antifungals through keratin-free cellulose...

Increased antifungal resistance is exacerbating the burden of invasive fungal infections, as well as potentially contributing to the increase in resistant dermatomycoses. In this commentary, we focus on antifungal drug resistance, in contrast to antibacterial resistance. We provide a brief historical perspective on the emergence of antifungal resis...

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 antif...

Background: Dermatophytoma, also described as a longitudinal streak/spike, is a form of onychomycosis that presents as yellow/white streaks or patches in the subungual space, with dense fungal masses encased in biofilm. This scoping review of the literature was conducted to address a general lack of information about the epidemiology, pathophysiolo...

Background: Antibiotic resistance is a global concern, with several countries reporting resistance in >50% of Cutibacterium acnes (C. acnes) strains. Combination formulations containing an antibiotic and the antimicrobial benzoyl peroxide (BPO) may reduce this resistance risk, especially with prolonged use. This four-part study tested susceptibilit...

A growing body of literature has marked the emergence and spread of antifungal resistance among species of Trichophyton , the most prevalent cause of toenail and fingernail onychomycosis in the United States and Europe. We review published data on rates of oral antifungal resistance among Trichophyton species; causes of antifungal resistance and me...

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. 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 stra...

Superficial mycoses, encompassing a range of fungal infections affecting the outer layers of the skin, hair, and nails, have become increasingly prevalent in recent years. While these infections are generally non-life-threatening, the emergence of antifungal resistance poses a growing threat to effective treatment strategies. In this article we exp...

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 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...

Background: Studies have demonstrated that the gut microbiome changes upon exposure to systemic antibiotics. There is a paucity of literature regarding impact on the gut microbiome by long-term usage of erythromycin ethyl succinate (EES) when utilized as a prokinetic. Methods: Stool samples from pediatric patients with feeding intolerance who re...

Aim: The primary aim of this clinical study was to determine if dietary supplementation with the probiotic, BIOHM FX (BFX), altered the gut microbiome balance following ingestion of 15g pea protein (PP) and enhanced the absorption of non-animal proteins determined via quantification of essential amino acids (EAAs). Thus, we compared the effects of...

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 mic...

We developed an oral Salmonella-based vaccine that prevents and reverses diabetes in non-obese diabetic (NOD) mice. Related to this, the gastrointestinal tract harbors a complex dynamic population of microorganisms, the gut microbiome, that influences host homeostasis and metabolism. Changes in the gut microbiome are associated with insulin dysfunc...

Introduction: We aim to assess the transcriptomic features of the single cell level to identify intracellular pathogens in patients with high grade bladder cancer. Methodology: CellRanger and Alevin were utilized to extract cell barcodes and unique molecular identifiers. After quality control, reads were aligned with human reference genome with Kra...

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, itra...

Background: The application of next-generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer (BC), these have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundame...

Background Recent studies have documented the complexity of the intestinal fungal community (‘mycobiome’) in mice, and clinical and experimental observations have shown that the mycobiome influences both gut health and disease, e.g., IBD. In fact, prior studies have shown that CD patients, compared to healthy controls, harbor higher levels of intes...

BACKGROUND Crohn’s disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to charac...

Treatment with neoadjuvant chemotherapy (NAC) in muscle invasive bladder cancer (MIBC) is associated with clinical benefit in urothelial carcinoma. While extensive research evaluating role of tumor mutational expression profiles and clinicopathologic factors into chemoresponse has been published, the role of gut microbiome (GM) in bladder cancer in...

The central role of gut microbiota in the regulation of health and disease has been convincingly demonstrated. Polymicrobial inter-kingdom interactions between bacteria (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 in...

Vulvovaginal candidiasis (VVC) is a common health-related issue and the second most common cause of vaginitis. Previously, azole antifungals were the mainstay of VVC treatment. Additionally, boric acid and nystatin have been used topically for management of VVC. Despite being effective and well tolerated by most patients, the use of azoles may be l...

Background: While microbiome and host regulation contribute independently to many disease states, it is unclear how circumcision in pediatric population influences subsequent changes in penile microbiome. Objective: Our study aims to analyze jointly paired taxonomic profiles and assess pathways implicated in inflammation, barrier protection, and...

The incidence of Candida auris, an emerging multidrug resistant fungal species, is increasing. The ability of this yeast to colonize the human skin could lead to infections. Thus, identifying agents to reduce the skin fungal burden is critical. In this study, using a murine skin model, we evaluated the efficacy of chlorhexidine formulated in a new...

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 c...

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...

Candida auris is an emerging, multi-drug resistant fungal pathogen that causes considerable morbidity and mortality. First identified in Japan in 2009, it has since been reported in more than 40 countries. C. auris can persist for long periods on different environmental surfaces as well as the skin. Clinical isolates are typically resistant to comm...

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...

Background Until recently, the properties of microbiome and mycobiome in humans and its relevance to disease have largely been unexplored. While the interest of microbiome and malignancy over the past few years have burgeoned with advent of new technologies, no research describing the composition of mycobiome in bladder cancer has been done. Deciph...

Background The application of next generation sequencing techniques has enabled characterization of urinary tract microbiome. Although many studies have demonstrated associations between the human microbiome and bladder cancer, they have not always reported consistent results, thereby necessitating cross-study comparisons. Thus, the fundamental que...

Background Increasing data indicates the gut flora including bacteria and fungi combined with environmental factors are important in the pathogenesis of colorectal cancer (CRC). Understanding differences in the microbiome in patients with colon neoplasia will foster the development of biomarkers for early detection.AimsDetermine the association of...

Recently, numerous cases of dermatophytosis resistant to terbinafine were reported. These cases have been increasing in frequency, with no improvement even with treatment using systemic therapies. Our objective was to determine the antifungal activity of efinaconazole compared to fluconazole, itraconazole, and terbinafine against dermatophyte, Cand...

With the gut microbiome being implicated in many diseases and even offering the potential for future therapies, its study has been gaining interest over the years. However, to gain more in-depth insight and understanding of the impact of the microbiome on our health, it is critical to have accurate microbial data that is reproducible and comparable...

Inflammatory bowel disease (IBD), a disorder characterized by chronic inflammation of the gastrointestinal (GI) tract and a range of adverse health effects including diarrhea, abdominal pain, vomiting, and bloody stools, affects nearly 3.1 million genetically susceptible adults in the United States today. Although the etiology of IBD remains unclea...

Background Recurrent vulvovaginal candidiasis (RVVC) affects nearly 138 million women globally each year. In the US, fluconazole is considered standard of care for acute vulvovaginal candidiasis (VVC), but there are currently no US Food and Drug Administration–approved drugs for the treatment of RVVC. Oteseconazole is a novel oral selective inhibit...

Simple Summary The role of the microbiome in health and disease has gained great attention over the past few decades. The evidence demonstrating the link between the microbiome and cancer has been growing. Although several studies have explored this topic, their main focus has been on bacteria, ignoring another important group in the microbiome: fu...

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. Important...

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...

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...

Onychomycosis is the most common nail condition seen in clinical practice, with significant impact on quality of life. Clinical examination alone is insufficient for accurate diagnosis, but mycological confirmation can be challenging during the COVID-19 pandemic. In this letter, a multidisciplinary panel of dermatologists, a podiatrist, dermatopath...

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 gastroent...

People living with HIV (PLWH) who are Immune Non-Responders (INR) persons are at greater risk of comorbidity and mortality than are Immune Responders (IR) who restore their CD4 T cells count (IR) after anti-retroviral therapy (ART). INR have low CD4-T cell counts (<350 c/ul), heightened systemic inflammation, and increased CD4-T cell cycling (Ki67+...

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...

541 Background: The role of microbiome in genitourinary cancer is an emerging field, with evidence implicating the important role of microbiome as causative factors or cofactors in tumorigenesis and drug metabolism. Our study aims to characterize healthy and bladder cancer enterotypes in the gut and identify functional alterations through the use o...

542 Background: Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon, breast and pancreatic cancer. However, the role of fungal mycobiome has not been evaluated in bladder cancer. With the sexual dimorphism that exists within bladder cancer (Bca) prevalence and survival, our study aims to characterize fungal mycobiome compos...

Recent studies have documented the complexity of the intestinal fungal community (‘mycobiome’) in mice, and clinical and experimental observations have shown that the mycobiome influences both gut health and disease, e.g., inflammatory bowel disease (IBD). In fact, prior studies have shown that Crohn’s disease (CD) patients, compared to healthy con...

This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a cri...

Candida auris is an emerging multidrug resistant Candida species that has been reported in many parts of the world for causing severe illness in hospitalized patients especially bloodstream infections. The challenge with this type of yeast is its resistance to commonly used antifungal drugs, thus identifying antifungals that are effective against t...

Background Recurrent vulvovaginal candidiasis (RVVC) affects nearly 138 million women globally each year. Currently there are no FDA approved treatments. The study was conducted to evaluate the efficacy of oral oteseconazole (VT-1161) in the prevention of culture-verified acute VVC episodes through Week 50 and compare the efficacy of oteseconazole...

Background Oteseconazole (VT-1161) is a novel, investigational oral therapy that is currently under FDA review for the treatment of recurrent vulvovaginal candidiasis (RVVC). Susceptibility testing was performed on all viable clinical isolates collected from three Phase 3 studies to determine the susceptibility of causative pathogens to oteseconazo...

Background & Aims We previously showed that abundance of C. tropicalis is significantly greater in Crohn’s disease patients compared to non-disease first-degree relatives. The aim of this study was to determine the effects and mechanisms of action of C. tropicalis infection on intestinal inflammation and injury in mice. Methods C57BL/6 mice were i...

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, w...

Objective: To evaluate the efficacy and safety of ibrexafungerp versus placebo for acute vulvovaginal candidiasis (VVC) treatment. Design: Global phase 3, randomised, placebo-controlled superiority study. Setting: Study sites in the USA (n = 19) and Bulgaria (n = 18). Population: Female patients aged ≥12 years with acute VVC and a vulvovagin...

Emerging data suggest healthy microbiome helps to protect against mucosal injury and inflammation. Dysbiosis results in biofilm formation in the gut which has been shown to be pro-inflammatory. MM patients potentially have significant dysbiosis result of long term corticosteroid use. Our group, previously showed that composition of microbiome prese...

Background: Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last publ...

The influence of microbiological species has gained increased visibility and traction in the medical domain with major revelations about the role of bacteria on symbiosis and dysbiosis. A large reason for these revelations can be attributed to advances in deep-sequencing technologies. However, the research on the role of fungi has lagged. With the...

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. St...

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 mi...

Antifungal activity of anidulafungin, voriconazole, isavuconazole, and fluconazole in the treatment of Candida auris was determined in vitro and in vivo. Minimum inhibitory concentrations (MICs) for Anidulafungin, voriconazole, isavuconazole, fluconazole, and amphotericin B were 0.5, 1, >64, 0.25, and 4 μg/mL, respectively. Significant in vivo effi...

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo . AmBisome showed MIC 50 and MIC 90 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...

Background: The rates of infection after inflatable penile prosthesis (IPP) range from 1% to 3%; however, with changes in antibiotic practice intraoperatively and the incorporation of local anesthetic dips, it is unclear whether this incidence of infection is affected. Aim: To evaluate whether the utilization of local anesthetic dips and antifun...

BACKGROUND Candida auris has demonstrated the ability to colonize the skin of hospitalized patients, possibly contributing to nosocomial spread. OBJECTIVE The objective was to determine whether two novel transdermal agents could clear skin colonization established by C. auris. METHODS A murine skin colonization model was first optimized and then...

In hosts with damaged or impaired immune systems such as those undergoing hematopoietic cell transplant (HCT) or intensive chemotherapy, breakthrough fungal infections can be fatal. Risk factors for breakthrough infections include severe neutropenia, use of corticosteroids, extended use of broad-spectrum antibiotics, and intensive care unit admissi...

Systemic infections caused by Candida species are an important cause of morbidity and mortality among immunocompromised and non-immunocompromised patients. In particular, Candida glabrata is an emerging species within the Candida family that causes infections ranging from superficial to life-threatening systemic disease. Echinocandins and azoles ar...

Echinocandins are a first-line therapy for Candida infections through their ability to inhibit the synthesis of polymer ß-(1,3)-D-glucan. However, there has been an emergence of multidrug-resistant fungal species necessitating the development of novel antifungal agents to combat invasive fungal infections. SCY-247, a second-generation glucan syntha...

Due to the increase of antifungal drug resistance and difficulties associated with drug administration, new antifungal agents for invasive fungal infections are needed. SCY-247 is a second-generation fungerp antifungal compound that interferes with the synthesis of the fungal cell wall polymer ß-(1,3)-D-glucan. We conducted an extensive antifungal...