Mahmoud A Ghannoum

Case Western Reserve University | CWRU · Department of Dermatology (University Hospitals Case Medical Center)

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...

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...

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...

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...

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...

Cancer is among the leading causes of death globally. Despite advances in cancer research, a full understanding of the exact cause has not been established. Recent data have shown that the microbiome has an important relationship with cancer on various levels, including cancer pathogenesis, diagnosis and prognosis, and treatment. Since most studies...

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...

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...

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...

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...

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...

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...

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...

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...

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...

We previously found that the elevated abundance of the fungus Candida tropicalis is positively correlated with the bacteria Escherichia coli and Serratia marcescens in Crohn’s disease patients and the three pathogens, when co-cultured, form a robust mixed-species biofilm. The finding suggests that these three pathogens communicate and promote biofi...

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...

Invasive fungal diseases continue to cause substantial mortality in the enlarging immunocompromised population. It is fortunate that the field has moved past amphotericin B deoxycholate as the only available antifungal drug but despite new classes of antifungal agents both primary and secondary drug resistance in molds and yeasts abound. From the r...

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increas...

Candida auris has shown to have high risk of skin colonization in hospital 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 signific...

Background: The incidence of type 1 diabetes (T1D) and overweight/obesity is on the rise. Previous studies showed altered gut microbiota in children with T1D where gut microbial differences between obese and lean children without diabetes were reported. The purpose of the study was to characterize the microbial composition of lean and overweight ch...

Background We determined levels of 11 soluble immune mediators in oral washings of ACTG A5254 participants with varying degrees of plasma viremia and CD4 T-cell counts to characterize the mucosal immune response at different stages of HIV-1 infection. Methods A5254 was a multicenter, cross-sectional study in people with HIV (PWH) recruited into 4-...

The effects of diversity of the gut microbiome on inflammation have centered mainly on bacterial flora. Recent research has implicated fungal species and their interactions with other organisms in the inflammatory process. New ways to restore microbial balance in the gut are being explored. Our goal was to identify beneficial probiotic strains that...

Purpose: This study assessed microbiome adherent to contact lenses and defined the bacterial communities associated with use of lens care solutions. Methods: Among 84 lenses screened for adherent ocular surface bacterial microbiome using 16S rRNA molecular amplification, 63 (75%) generated bacterial-specific amplicons processed using the Ion Tor...

Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent...

This pooled analysis evaluated the relationship of isavuconazole and voriconazole minimum inhibitory concentrations (MICs) of Aspergillus pathogens at baseline with all-cause mortality and clinical outcomes following treatment with either drug in the SECURE and VITAL trials. Isavuconazole and voriconazole may have had reduced efficacy against patho...

Small-molecule antivirulence agents represent a promising alternative or adjuvant to antibiotics. These compounds disarm pathogens of disease-causing toxins without killing them, thereby diminishing survival pressure to develop resistance. Here we show that the small-molecule antivirulence agents F12 and F19 block staphylococcal transcription facto...

Introduction: Atopic dermatitis (AD) is associated with changes in skin bacterial microbiome. Emollient treatment induces change in bacterial microbiome in AD, but its effect on fungal microbiome ("mycobiome") and their inter-kingdom correlations is unknown. We used Ion-Torrent sequencing to characterize the mycobiome of AD patients in response to...

Background The effect of smoking on microbial dysbiosis and the potential consequence of such shift on markers of HIV disease is unknown. Here we assessed the relationship of microbial dysbiosis with smoking and markers of HIV disease. Methods Oral wash was collected from: (1) HIV-infected smokers (HIV-SM, n = 48), (2) HIV-infected non-smokers (HI...

Clustering differences, based on distance to centroid, in samples from the three groups at different taxa in bacteria (A-F) and fungi (G-L). (TIF)

Unlike superficial fungal infections of the skin and nails, which are the most common fungal diseases in humans, invasive fungal infections carry high morbidity and mortality, particularly those associated with biofilm formation on indwelling medical devices. Therapeutic management of these complex diseases is often complicated by the rise in resis...

The adult intestine hosts a myriad of diverse bacterial species that reside mostly in the lower gut maintaining a symbiosis with the human habitat. In the current review, we describe the neoteric advancement in our comprehension of how the gut microbiota communicates with the skin as one of the main regulators in the gut-skin axis. We attempted to...

Central line associated bloodstream infections (CLABSIs) are increasingly recognized to be associated with intralumenal microbial biofilms, and effective measures for the prevention and treatment of BSI remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL) containing trimethoprim (5 mg/ml) and...

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...

Central line associated bloodstream infections (CLABSIs) are increasingly recognized to be associated with intralumenal microbial biofilms, and effective measures for the prevention and treatment of BSI remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL) containing trimethoprim (5 mg/ml) and...

Background Epidemiological studies indicate that the use of artificial sweeteners doubles the risk for Crohn’s disease (CD). Herein, we experimentally quantified the impact of 6-week supplementation with a commercial sweetener (Splenda; ingredients sucralose maltodextrin, 1:99, w/w) on both the severity of CD-like ileitis and the intestinal microbi...

Objective: To characterize the oral bacterial microbiome in HIV-infected participants at baseline and after 24 weeks of EFV/FTC/TDF. Design: Thirty-five participants co-enrolled in two AIDS Clinical Trials Group (ACTG) studies, A5272 and A5280, with paired saliva samples and complete data sets were assessed. Methods: Paired saliva samples were...

This is the first book ever to be published on this topic! Comprehensively packed with up-to-date research information, this volume is written with both the beginner and the established research expert in mind. Complemented with tables, line drawings, and photographs, this resource provides background material which allows the reader to become fami...

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 minimum inhibitory concentration values, and some strains are resistant to all 3 major antifungal classes. Here we evaluated the...