Hyaline Molds Research Articles

Invasive Fungal Infections of the Head and Neck: A Tertiary Hospital Experience.

From the existing millions of fungal species, only a few cause disease. In this study, we investigated invasive fungal infections in the head and neck (H&N) over a 19-year period (2005 to 2024) at a large academic healthcare system. Among the 413 documented fungal H&N infections, 336 were noninvasive, and 77 were invasive. The highest incidence of invasive infections occurred in the sinonasal cavities, with a 15-fold difference compared to other sites. Most infections affected adults over 40 years old. The most common organisms were Mucorales (51%), hyaline molds (29%), and Candida (11%). Risk factors included malignancy, transplant, diabetes, and illicit drug use. Mortality was high in patients with malignancy and/or transplant. Infections affecting the mandible were usually a complication of osteoradionecrosis and were associated with the coinfection of Candida and Actinomyces. At other sites, infections were rare and were usually the result of penetrating injuries or immunosuppression. Treatment typically involved a combination of antifungals and surgical procedures.

Non-Aspergillus Hyaline Molds: A Host-Based Perspective of Emerging Pathogenic Fungi Causing Sinopulmonary Diseases.

The incidence of invasive sino-pulmonary diseases due to non-Aspergillus hyaline molds is increasing due to an enlarging and evolving population of immunosuppressed hosts as well as improvements in the capabilities of molecular-based diagnostics. Herein, we review the following opportunistic pathogens known to cause sinopulmonary disease, the most common manifestation of hyalohyphomycosis: Fusarium spp., Scedosporium spp., Lomentospora prolificans, Scopulariopsis spp., Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, Rasamsonia argillacea species complex, Arthrographis kalrae, and Penicillium species. To facilitate an understanding of the epidemiology and clinical features of sino-pulmonary hyalohyphomycoses in the context of host immune impairment, we utilized a host-based approach encompassing the following underlying conditions: neutropenia, hematologic malignancy, hematopoietic and solid organ transplantation, chronic granulomatous disease, acquired immunodeficiency syndrome, cystic fibrosis, and healthy individuals who sustain burns, trauma, or iatrogenic exposures. We further summarize the pre-clinical and clinical data informing antifungal management for each pathogen and consider the role of adjunctive surgery and/or immunomodulatory treatments to optimize patient outcome.

Nanotechnology-Based Approaches for Voriconazole Delivery Applied to Invasive Fungal Infections.

Invasive fungal infections increase mortality and morbidity rates worldwide. The treatment of these infections is still limited due to the low bioavailability and toxicity, requiring therapeutic monitoring, especially in the most severe cases. Voriconazole is an azole widely used to treat invasive aspergillosis, other hyaline molds, many dematiaceous molds, Candida spp., including those resistant to fluconazole, and for infections caused by endemic mycoses, in addition to those that occur in the central nervous system. However, despite its broad activity, using voriconazole has limitations related to its non-linear pharmacokinetics, leading to supratherapeutic doses and increased toxicity according to individual polymorphisms during its metabolism. In this sense, nanotechnology-based drug delivery systems have successfully improved the physicochemical and biological aspects of different classes of drugs, including antifungals. In this review, we highlighted recent work that has applied nanotechnology to deliver voriconazole. These systems allowed increased permeation and deposition of voriconazole in target tissues from a controlled and sustained release in different routes of administration such as ocular, pulmonary, oral, topical, and parenteral. Thus, nanotechnology application aiming to delivery voriconazole becomes a more effective and safer therapeutic alternative in the treatment of fungal infections.

Title Causative agents distribution of isolated from dermatomycoses in Eskişehir city hospital Sort Title Superficial fungal infections

Abstract Objective Dermatomycoses are superficial fungal infections of the skin, hair and nails. The fungi responsible for dermatomycoses include dermatophytes, yeasts and non-dermatophytic molds (NDM). Onychomycosis is the most common nail disease caused by dermatophytes, NDMs, and yeasts with a worldwide. This study was under taken to investigate the current distribution of aetiological agents of dermatomycoses. Materials and Methods In this study, we evaluated the microscopic examination and culture results of the samples taken from the patients who applied to our clinic for two year. Species were identification on the basis of combined clinical pictures, culture and microscopic morphology characters of together. Results During the study period, 592 samples were examined. The distribution of isolates was found to be 118 (47.2%) NDM, 66 (26.4%) dermatophytes and 66 (26.4%) yeasts, respectively. Tinea unguium was the most prevalent type of dermatophytoses. T. rubrum was most frequent aetiological agents of detected in patients. According to our study, 22% of non-dermatophyte hyaline molds are Fusarium spp. and 21% are Aspergillus spp. species. Conclusion Several studies have shown that both the prevalence and aetiology of dermatomycoses can change according to geographical location, climatic conditions, personal factors. The objective of our study was to analyse 2 years of epidemiological data regarding dermatological mycology testing performed in a large tertiary care teaching hospital in Eskişehir, This report represents the most comprehensive analysis of this type from Eskişehir, and it is hoped that its findings will be of interest to, and inform, researchers and clinicians focused on mycoses and international epidemiology. To the best of our knowledge, we provide the first analysis from Eskisehir of fungal detections from all external body site (skin, hair and nail).

351. Epidemiology and antifungal susceptibilities of clinically significant filamentous fungi from a tertiary hospital in Singapore from 2018 – 2021

Abstract Background Filamentous fungi infections are associated with significant morbidity. Although an increase in antifungal resistance has been reported globally, no data pertaining to Singapore is available. This study investigates the species distribution and antifungal susceptibility profiles of molds isolated from a tertiary hospital in Singapore. Methods A retrospective review of fungal cultures with antifungal susceptibility results reported in the laboratory information system from 2018 to 2021 was conducted. Unique isolates per patient were included. Molds were identified primarily by morphology. Molecular studies were used as an adjunct where required. Susceptibility testing was performed via broth microdilution (Sensititre YeastOne) and gradient diffusion (Liofilchem) methods. Results 125 isolates were analyzed (Table 1). The most common molds recovered were Aspergillus, Fusarium and Mucorales. Aspergillus and Mucorales frequently involved the respiratory tract and skin and soft tissue (SSTI) whereas Fusarium was isolated from SSTI and blood. Amphotericin B had moderate activity against all molds, with only 11 out of 88 isolates (12.5%) being non-wild type (Table 2). The echinocandins exhibited good activity against Aspergillus and other hyaline molds but not Fusarium and Mucorales. The triazoles were most useful against Aspergillus, with posaconazole demonstrating the lowest geometric mean of 0.067. Fusarium had high MICs when tested against the azoles. Posaconazole was the azole of choice for Mucorales. Six Aspergillus isolates (all A. fumigatus) were non-wild type when tested against voriconazole, with a MIC >1. Of these six isolates, three were also non-wild type for amphotericin B, with a MIC >2. In particular, one Aspergillus fumigatus complex isolate demonstrated resistance across all tested azoles and sequencing revealed Cyp51 mutations. Conclusion Aspergillus species is the most prevalent clinically significant mold in our hospital. Although triazoles and echinocandins exhibit good activity, 13.33% of Aspergillus isolates were non-wild type for amphotericin B. Given the detection of these non-wild type Aspergillus species, susceptibility testing may be indicated in seriously ill patients to aid clinicians in selecting antifungal therapy. Disclosures All Authors: No reported disclosures.

Osteoarticular Mycoses.

Osteoarticular mycoses are chronic debilitating infections that require extended courses of antifungal therapy and may warrant expert surgical intervention. As there has been no comprehensive review of these diseases, the International Consortium for Osteoarticular Mycoses prepared a definitive treatise for this important class of infections. Among the etiologies of osteoarticular mycoses are Candida spp., Aspergillus spp., Mucorales, dematiaceous fungi, non-Aspergillus hyaline molds, and endemic mycoses, including those caused by Histoplasma capsulatum, Blastomyces dermatitidis, and Coccidioides species. This review analyzes the history, epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, inflammatory biomarkers, diagnostic imaging modalities, treatments, and outcomes of osteomyelitis and septic arthritis caused by these organisms. Candida osteomyelitis and Candida arthritis are associated with greater events of hematogenous dissemination than those of most other osteoarticular mycoses. Traumatic inoculation is more commonly associated with osteoarticular mycoses caused by Aspergillus and non-Aspergillus molds. Synovial fluid cultures are highly sensitive in the detection of Candida and Aspergillus arthritis. Relapsed infection, particularly in Candida arthritis, may develop in relation to an inadequate duration of therapy. Overall mortality reflects survival from disseminated infection and underlying host factors.

P276 Molecular epidemiology of clinical filamentous fungi in Qatar beyond Aspergillus and Fusarium

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectivesDue to an increasing number of patients at risk, (ie, with a highly compromised immune system and/or receiving aggressive chemotherapy treatment), invasive fungal infections (IFI) are increasingly being reported. They are associated with significantly high mortality rates. Aspergillus spp., particularly A. fumigatus, is the major cause of mold-related IFI around the world followed by Fusarium spp., however, other molds are emerging as human pathogens. The aim of this study was to explore the epidemiology and prevalence of the non-Aspergillus and non-Fusarium molds in human clinical samples over 11 years period in Qatar based tertiary hospital using molecular techniques.MethodsA total of 91 clinical specimens positive for molds belonging to 90 patients were recorded in about 11 years (September 2003 to November 2014). The isolates were identified based on morphological characteristics and by sequencing the internal transcribed spacer (ITS) gene. To confirm the identifications, a phylogenetic tree based on ITS sequences was constructed.ResultsMost patients were males (72%), 6% were immunocompromised, 12% had IFI, and 7% died within 30 days of diagnosis. The fungal isolates were recovered from a variety of clinical samples, including nails, skin, hair, scalp, nasal cavity, wounds, respiratory samples, body fluids, eye, ear, tissue, abscess, and blood specimens. Dematiaceous fungi were overall the most isolated (33/91, 36%), followed by dermatophytes (25/91, 27%), Mucorales (16/91, 18%), and other hyaline molds (17/91, 19%) (Fig. 1). Curvularia was the most isolated genus (22/91, 24%) and Mucorales were the major cause of IF (5/11, 45.5%) (Table 1). Superficial mycoses were caused by dermatophytes (66%) and non-dermatophytes (34%). Furthermore, rare fungi that are not commonly known to cause human disease were recovered such as Rhytidhysteron rufulum, Subramaniula asteroids, Dothichiza pimprina, and Quambalaria cyanescens.ConclusionThe current study highlights the epidemiology and spectrum of mold genera, other than Aspergillus and Fusarium, recovered from human clinical samples in Qatar, which can aid in surveillance of uncommon and emerging mycoses other than aspergillosis and fusuriosis.

P216 Rare isolates from subcutaneous mycotic lesions; A study from tertiary care center in Chhattisgarh, India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMAims and ObjectiveTo identify the causative agents of suspected subcutaneous mycosis patients attending to a tertiary care hospital, Chhattisgarh, India.IntroductionSubcutaneous mycoses are a group of fungal infections of dermis and subcutaneous tissue caused by both melanized and hyaline molds. It often affects patients with immunosuppressive conditions. It consists of Sporotrichosis, Chromoblastomycosis, Phaeohyphomycosis, Hyalohyphomycosis, Mycetoma, subcutaneous zygomycosis, Rhinosporidiosis, Lobomycosis, and disseminated Penicilliosis. There are proven pathogenic agents causing subcutaneous mycosis though are not regularly isolated and reported. Few of them are commonly come across in the laboratory. Herewith, emphasized on the unusual clinical isolates from the patients having subcutaneous mycotic lesions with their clinical details.MethodIt is a retrospective descriptive analysis of data of subcutaneous mycosis cases of duration January 2019 to March 2022.Total 52 clinical specimens from the suspected subcutaneous mycotic lesion were studied. Male dominance was observed amongst the patients. Amongst 52, 31% were detected positive for fungal elements by direct microscopy in 20% KOH mount, 55.7%, 25% positivity was observed in Culture and by both KOH wet mount and culture. Samples were processed and identified by using standard protocol.The significant unusual isolates identified were Conidiobolus coronatus from subcutaneous cyst from buttocks, Medicopsis romerai from fine needle aspiration from the nodule of left thumb, Rhytidhysteron rufulum from right lateral malleolus, Aquastroma magniostiolata species from subcutaneous cyst on lateral aspect of left lower leg above lateral malleolus, Aspergillus tamorii, Aspergillus glaucus, Chetomium species, Aspergillus montevidensis, Cladosporium sphaerospermum. Phenotypically unidentified isolates were sent to NCCPF PGI, Chandigarh for final identification.ConclusionThere is diversity in the etiological agents of subcutaneous mycoses. Every case is different and rare. With the help of molecular techniques, it became possible to identify unusual fungal isolates from subcutaneous infection. Awareness and extensive studies are required to evidence the pathogenicity and associated complication due to these fungal infections. It will also help to regulate the therapeutic management and to know the geographical distribution of unusual fungal agents.

Predictors and outcomes of peritoneal dialysis-related infections due to filamentous molds (MycoPDICS).

We sought to evaluate the predictors and outcomes of mold peritonitis in patients with peritoneal dialysis (PD). This cohort study included PD patients from the MycoPDICS database who had fungal peritonitis between July 2015-June 2020. Patient outcomes were analyzed by Kaplan Meier curves and the Log-rank test. Multivariable Cox proportional hazards model regression was used to estimating associations between fungal types and patients' outcomes. The study included 304 fungal peritonitis episodes (yeasts n = 129, hyaline molds n = 122, non-hyaline molds n = 44, and mixed fungi n = 9) in 303 patients. Fungal infections were common during the wet season (p <0.001). Mold peritonitis was significantly more frequent in patients with higher hemoglobin levels, presentations with catheter problems, and positive galactomannan (a fungal cell wall component) tests. Patient survival rates were lowest for non-hyaline mold peritonitis. A higher hazard of death was significantly associated with leaving the catheter in-situ (adjusted hazard ratio [HR] = 6.15, 95%confidence interval [CI]: 2.86-13.23) or delaying catheter removal after the diagnosis of fungal peritonitis (HR = 1.56, 95%CI: 1.00-2.44), as well as not receiving antifungal treatment (HR = 2.23, 95%CI: 1.25-4.01) or receiving it for less than 2 weeks (HR = 2.13, 95%CI: 1.33-3.43). Each additional day of antifungal therapy beyond the minimum 14-day duration was associated with a 2% lower risk of death (HR = 0.98, 95%CI: 0.95-0.999). Non-hyaline-mold peritonitis had worse survival. Longer duration and higher daily dosage of antifungal treatment were associated with better survival. Deviations from the 2016 ISPD Peritonitis Guideline recommendations concerning treatment duration and catheter removal timing were independently associated with higher mortality.

Practical Approach to the Pathologic Diagnosis of Mixed Filamentous Fungal Infections in Burn Wounds: A Case Series

Abstract Introduction/Objective Opportunistic infections by fungi are a major source of morbidity and mortality in patients suffering from extensive burn wounds. Here we review a series of cases of infections by multiple fungi in burn wounds as diagnosed by histopathology and outline the key features for the pathologist to include in the report. Methods/Case Report Biopsies from patients with more than one fungal species identified in the laboratory in a concurrent culture or by PCR were included in this study. Three cases are presented with multiple fungi identified. Each case had yeast and at least one different hyaline mold species present on pathology; two cases additionally had mucormycetes present, with angioinvasion in one case. All organisms requiried microbiologic cultures and variably required molecular testing for full identification. Results (if a Case Study enter NA) N/A Conclusion Pathologists should be aware of the possibility of infection by multiple fungal species in burn wounds. Fungal morphology in tissue sections should allow for detection and distinction of mucormyctes and other hyaline molds. Histopathologic correlation with culture and/or PCR results is essential to distinguish potential contaminants from true infection.

Recovery and Its Dynamics of Filamentous Fungi from Clinical Specimen Cultures: An Extensive Study.

ABSTRACTThe culture method remains vital in diagnosing fungal infections, but extensive data-based evaluation of the method, especially for filamentous fungi (molds), is minimal. The purpose of this study was to characterize mold recoveries from fungal cultures and the impact of media and incubation duration. Clinical specimens for fungal cultures were submitted primarily from the eastern and central United States, and mold isolation data were prospectively collected and analyzed. A total of 1,821 molds in 59 genera were isolated from 1,687 positive specimens, accounting for approximately 5.6% of our cohort of 30,000 fungal cultures. Within 2 weeks, nearly 90% of molds and 97.3% of Aspergillus fumigatus complex were recovered (>95% confidence interval [CI]). All Mucorales fungi were recovered within 11 days of incubation. The recovery peak time was day 3 for Mucorales fungi, day 4 for hyaline molds, day 5 for dematiaceous molds, and day 7 for Onygenales fungi. The recovery of Histoplasma capsulatum and Trichophyton species in the fourth week of incubation reveals that a 3-week incubation time is insufficient. Inhibitory mold agar was the best medium for recovering all mold types among all tested specimen types, yielding nearly 78% of mold growth overall, indicating the necessity of selective medium for fungal cultures.IMPORTANCE Fungal culture is the gold standard method of diagnosing fungal infections, but important information, such as the impact of media and incubation times on fungal recovery, is not well documented. This study addressed these gaps using extensive data-based evaluation focused on molds. We identified the best medium types and incubation times for better fungal culture practice. We analyzed 1,821 molds from 1,687 positive specimens in our cohort of approximately 30,000 fungal cultures. Mold recovery peaked between 3 and 7 days of incubation, dependent upon the type of mold. Some well-defined fungal pathogens, such as Histoplasma capsulatum and Trichophyton species, were isolated in the fourth week of incubation. Inhibitory mold agar was identified as the best medium for recovering all mold types among all tested specimen sources. As we are aware, this is the largest study of fungal culture methods and supports 4 weeks of incubation for optimal mold recovery.

Scedosporium and Lomentospora Infections Are Infrequent, Difficult to Diagnose by Histology, and Highly Virulent.

To further characterize the histomorphology and clinicopathologic features of colonization and invasive disease by Scedosporium and Lomentospora. We conducted a 20-year retrospective study. Patients with at least 1 histopathology specimen and concurrent culture were included. Clinical features, histopathology, microbiology, and outcomes were analyzed. Eighteen patients were identified, and all were immunocompromised. Eight patients had colonization, while 10 had invasive disease (pneumonia [n = 3], skin and soft-tissue infections [n = 3], disseminated disease [n = 4]). Scedosporium apiospermum was identified in 15 patients, Lomentospora prolificans in 2 patients, and Scedosporium ellipsoideum in 1 patient. Fungal elements were identified histologically in 11 patients. Granulomatous, suppurative, and necrotizing inflammation with irregular branching hyphae and characteristic microconidia were observed in 9 cases; conidiogenous cells were identified in 4 cases. Seven patients died of invasive disease despite therapy, and 3 recovered after treatment. No deaths were observed in patients with colonization. Scedosporium and Lomentospora are rare, virulent opportunistic fungal pathogens. Fungal morphology may overlap with other hyaline molds, but identification of obovoid conidia should allow a diagnosis of non-Aspergillus hyalohyphomycosis and consideration of Scedosporium and Lomentospora. Histopathologic correlation with culture and polymerase chain reaction is critical for diagnosis and treatment.

Antifungal susceptibility of clinical mould isolates in New Zealand, 2001–2019

The objective of this study was to review the antifungal susceptibility of clinical mould isolates performed by the New Zealand Mycology Reference Laboratory. Isolates were either local or referred for testing from other New Zealand laboratories. All isolates were tested by the broth colorimetric microdilution method, Sensititre YeastOne (SYO). Epidemiological cut-off values (ECVs) derived from either the Clinical and Laboratory Standards Institute (CLSI) method or SYO were used to determine the proportion of non-wild type (non-WT) isolates, i.e., those with an increased likelihood to harbour acquired mechanisms of resistance. A total of 614 isolates were tested. Most isolates (55%) were from the respiratory tract followed by musculoskeletal tissue (17%), eye (10%) and abdomen (5%). The azoles had similar activity except for voriconazole which was less active against the Mucorales. The echinocandins had good activity against Aspergillus spp., other hyaline moulds and dematiaceous isolates but were inactive against Fusarium spp., Lomentospora prolificans and the Mucorales. Amphotericin B had best activity against the Mucorales. The two least susceptible groups were Fusarium spp. and L.prolificans isolates. Three Aspergillus isolates were non-WT for amphotericin B, and four non-WT for azoles. Non-WT were not encountered for caspofungin. Non-Aspergillus isolates in New Zealand have susceptibility patterns similar to those reported elsewhere. In contrast to a growing number of other countries, azole resistance was rare in A.fumigatus sensu stricto. Non-WT isolates were uncommon. The results provide a baseline for monitoring emerging antifungal resistance in New Zealand and support current Australasian treatment guidelines for invasive fungal infections.

Non-Aspergillus Hyaline Molds: Emerging Causes of Sino-Pulmonary Fungal Infections and Other Invasive Mycoses.

Hyaline molds, widely distributed in nature, are an important and increasing cause of invasive fungal infections in humans, likely due to an expanding population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. Sinopulmonary disease and disseminated infection are common manifestations in neutropenic patients and transplant recipients, whereas, catheter-related and localized soft tissue infections predominate in immunocompetent hosts. These organisms are not reliably differentiated based on their morphology in tissue; rather, efforts should be made to establish a microbiologic diagnosis via culture or molecular-based methods to guide antifungal management and inform prognosis. Herein, we review the epidemiology, clinical manifestations, diagnosis, and management of these opportunistic pathogens known to cause hyalohyphomycoses: Scedosporium spp., Lomentospora prolificans, Fusarium spp., Scopulariopsis spp., Arthrographis kalrae, Trichoderma spp., Acremonium spp., Paecilomyces variotii, Purpureocillium lilacinum, and Penicillium species.

Updates on the Treatment of Non-Aspergillus Hyaline Mold Infections

This review summarizes both the recent and relevant studies about the treatment of non-Aspergillus hyaline molds. Given the rarity of these infections, there have been no large randomized clinical trials regarding the most effective antifungal therapy. Although there are more data for the treatment of Fusarium and Scedosporium, there are limited data with case reports that address the other rare hyalohyphomycetes. As we develop improved diagnostic techniques and larger fungal registries, we may be able to determine efficacious treatment modalities. We hope that future research will focus on implementing clinical trials with the new antifungals and ongoing development of novel fungal agents.

Central Nervous System Infections Due to Aspergillus and Other Hyaline Molds.

Central nervous system infections due to Aspergillus spp and other hyaline molds such as Fusarium and Scedosporium spp are rare but fatal conditions. Invasion of the central nervous system (CNS) tends to occur as a result of hematogenous dissemination among immunocompromised patients, and by local extension or direct inoculation secondary to trauma in immunocompetent hosts. Efforts should be directed to confirm the diagnosis by image-guided stereotactic brain biopsy when feasible. Non-culture methods could be useful to support the diagnosis, but they have not been validated to be performed in cerebral spinal fluid. Treatment of these infections is challenging given the variable susceptibility profile of these pathogens and the penetration of antifungal agents into the brain.

Fusarium spp., a Genus of Common Plant Pathogens That Can Cause Devastating, Opportunistic Human Disease

Fusarium spp. are environmental hyaline molds that are pathogens in plants and opportunistic pathogens in humans. In immunocompetent individuals, Fusarium sp. infections primarily include keratitis, onychomycosis, and localized infections due to trauma. However, in immunocompromised patients, particularly those with hematological malignancies, members of this genus can cause devastating, invasive, and disseminated infections with high mortality. In general, these species are resistant to therapy with a variety of antifungal agents. This article reviews recent literature about human infections caused by Fusarium spp., treatment and outcomes, and methods for accurately identifying isolates recovered from clinical specimens.

Voriconazole: How to Use This Antifungal Agent and What to Expect.

Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black molds. It is also effective for infections caused by Candida species, including those that are fluconazole resistant, and for infections caused by the endemic mycoses, including those that occur in the central nervous system. It has the advantage of being available in both an intravenous and an oral formulation that is well absorbed. Drawbacks to the use of voriconazole are that it has unpredictable, nonlinear pharmacokinetics with extensive interpatient and intrapatient variation in serum levels. Some of the adverse effects seen with voriconazole are related to high serum concentrations, and, as a result, therapeutic drug monitoring is essential when using this agent. Drug-drug interactions are common, and possible interactions must be sought before voriconazole is prescribed. With prolonged use, newly described adverse effects, including periostitis, alopecia, and development of skin cancers, have been noted.

Disruption of Fungi Cell Membranes by Polyenes, Azoles, Allylamines, Amino Acids and Peptides

The fungal cell membrane is one of the targets for some groups of antifungal agents: the polyenes, lipodepsinonapeptides, amino acids and other peptides, which interferes with the structural integrity of the lipid bilayer. Polyene antifungals show effectiveness against sterol-containing organisms by interacting directly with the fungal ergosterol. Amphotericin B exhibits activity against most species of Candida, Cryptococcus neoformans, most Aspergillus sp., hyaline molds, Penicillium, Paecilomyces, and Scopulariopsis, dimorphic fungi including Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, and Paracoccidioides brasiliensis. Nystatin binds to sterols in the cell membrane of yeasts resulting in electrolyte leakages. Statins are competitive inhibitors of HMG-CoA reductase, which is involved in the ergosterol synthesis. The azoles specifically inhibits the cytochrome P450 enzyme CYP51, resulting in interruption of membrane synthesis, depletion of ergosterol leading to an increase in toxic methylated sterol precursors in the cell membrane. The morpholines are synthetic antifungals and inhibits the reductase and isomerase enzymes in ergosterol biosynthesis triggering accumulation of dimethyllanosterol and depletion of ergosterol. Aureobasidins are highly lipophilic and act by inhibiting inositol phosphoceramide (IPC) synthase, critical in fungal sphingolipid biosynthesis thereby depleting essential sphingolipids in the fungal cells. The lipopeptide iturin acts by increasing membrane permeabilization in fungal cell. Lipodepsinonapeptides produced by Pseudomonas syringae interacts with the fungal cell membrane by pore formation resulting in fatal electrolytic leakage. Syringomycins form ion channels in the fungal plasma membrane employing a novel sphingolipid-modulated channel formation mechanism while Pseudomycin A alters several membrane functions like membrane potential, protein phosphorylation, H1-ATPase activity, and cation transport fluxes.

Acremonium-Associated CLABSI in a Multiple Myeloma Patient: Pitfalls in Diagnosis: A Rare Case Report

Acremonium species are hyaline hyphomycetes that are ubiquitous environmental contaminants occasionally involved in infections, including onychomycosis, keratitis, or even mycetoma. However, aggressive use of newer medical technologies like potent chemotherapy protocols and invasive central-line catheters and newer diseases like HIV infection have resulted in Acremonium and other hyaline molds being increasingly reported as the cause of fungemia. We present …