Antifungal Treatment Research Articles

Epigenetic modulation of fungal pathogens: a focus on Magnaporthe oryzae

Epigenetics has emerged as a potent field of study for understanding the factors influencing the effectiveness of human disease treatments and for identifying alternations induced by pathogens in host plants. However, there has been a paucity of research on the epigenetic control of the proliferation and pathogenicity of fungal plant pathogens. Fungal plant pathogens such as Magnaporthe oryzae, a significant threat to global rice production, provide an important model for exploring how epigenetic mechanisms govern fungal proliferation and virulence. In M. oryzae, epigenetic alterations, such as DNA methylation, histone modification, and non-coding RNAs, regulate gene expression patterns that influence the pathogen’s ability to infect its host. These modifications can enhance fungal adaptability, allowing the pathogen to survive in diverse environments and evade host immune responses. Our primary objective is to provide a comprehensive review of the existing epigenetic research on M. oryzae and shed light on how these changes influence the pathogen’s lifecycle, its ability to invade host tissues, and the overall severity of the disease. We begin by examining the epigenetic alterations occurring in M. oryzae and their contributions to the virulence and proliferation of the fungus. To advance our understanding of epigenetic mechanisms in M. oryzae and similar plant diseases, we emphasize the need to address unanswered questions and explore future research directions. This information is crucial for developing new antifungal treatments that target epigenetic pathways, which could lead to improved disease management.

Fungal Skin Infections in Beach Volleyball Athletes in Greece

Background/Objectives: Fungal infections, commonly referred to as mycoses, are widespread and affect various parts of the body. Common types of fungal skin infections include tinea pedis, tinea unguim, tinea cruris, tinea versicolor, and tinea manuum. Athletes, in particular, are at a higher risk of contracting these infections due to several factors inherent to their training and competitive environments. Methods: This research examined the incidence, anatomical distribution, and seasonal occurrence of fungal skin infections among beach volleyball athletes in Greece. The study cohort consisted of 785 participants, with an average age of 28.4 years. Variables recorded included gender, the seasonal periods during which athletes might be more prone to injuries, and the specific body areas affected by fungal infections. In addition, training-related data such as weekly training frequency, and daily training duration were collected. Results: Incidence rates correlated in relation to gender: male, tinea pedis (p < 0.000), tinea manuum (p < 0.010); number of weekly trainings: tinea pedis (p < 0.000), tinea unguium (p < 0.043), tinea cruris (p < 0.008), tinea versicolor (p < 0.038), tinea manuum (p < 0.043); average hours of daily training: tinea unguium (p < 0.039), tinea manuum (p < 0.039). Conclusions: Athletic activities often involve exposure to warm, moist conditions that promote fungal growth. Locker rooms, showers, and equipment can harbor fungi, spreading infections among athletes. Understanding these infections is essential for effective prevention and management, as they can impact performance and health if untreated. Proper hygiene, antifungal treatments, and public health measures are crucial to reducing the risk in athletic settings.

Multiplex antimicrobial activities of the self-assembled amphiphilic polypeptide β nanofiber KF-5 against vaginal pathogens

BackgroundVaginal infections caused by multidrug-resistant pathogens such as Candida albicans and Gardnerella spp. represent a significant health challenge. Current treatments often fail because of resistance and toxicity. This study aimed to synthesize and characterize a novel amphiphilic polypeptide, KF-5, and evaluate its antibacterial and antifungal activities, biocompatibility, and potential mechanisms of action.ResultsThe KF-5 peptide was synthesized via solid-phase peptide synthesis and self-assembled into nanostructures with filamentous and hydrogel-like configurations. Characterization by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic force microscopy (AFM) confirmed the unique nanostructural properties of KF-5. KF-5 (125, 250, or 500 µg/ml) demonstrated potent antibacterial and antifungal activities, with significant inhibitory effects on drug-resistant Candida albicans and Gardnerella spp. (P < 0.05). In vitro assays revealed that 500 µg/ml KF-5 disrupted microbial cell membranes, increased membrane permeability, and induced lipid oxidation, leading to cell death (P < 0.05). Cytotoxicity tests revealed minimal toxicity in human vaginal epithelial cells, keratinocytes, and macrophages, with over 95% viability at high concentrations. Molecular dynamics simulations indicated that KF-5 interacts with phospholipid bilayers through electrostatic interactions, causing membrane disruption. In vivo studies using a mouse model of vaginal infection revealed that 0.5, 1, and 2 mg/ml KF-5 significantly reduced fungal burden and inflammation, and histological analysis confirmed the restoration of vaginal mucosal integrity (P < 0.01). Compared with conventional antifungal treatments such as miconazole, KF-5 exhibited superior efficacy (P < 0.01).ConclusionsKF-5 demonstrates significant potential as a safe and effective antimicrobial agent for treating vaginal infections. Its ability to disrupt microbial membranes while maintaining biocompatibility with human cells highlights its potential for clinical application. These findings provide a foundation for further development of KF-5 as a therapeutic option for combating drug-resistant infections.

Long-Term Antifungal Treatment in a Patient With Confirmed Allergic Bronchopulmonary Aspergillosis

Long-Term Antifungal Treatment in a Patient With Confirmed Allergic Bronchopulmonary Aspergillosis

Three-Dose Antifungal Treatment Improves the Efficacy for Severe Vulvovaginal Candidiasis

Vulvovaginal candidiasis (VVC) is a prevalent gynecological infection characterized by high incidence and recurrent episodes, causing significant distress in women. This study aims to assess the effectiveness of different clotrimazole and fluconazole treatment regimens for severe vulvovaginal candidiasis (SVVC). A retrospective analysis was conducted on 1303 cases of SVVC among first-time visitors to the gynecology outpatient department at Peking University Shenzhen Hospital between January 2013 and December 2022. Vaginal secretions were systematically collected for fungal culture, with species identification conducted using Chromogenic culture medium and API Candida test reagents. Mycological cure rates were assessed at days 7–14, days 25–35, and day 35 to 6 months after treatment. The three-dose clotrimazole regimen demonstrated significantly higher mycological cure rates (85.7%, 80.0% and 74.6% at three follow-up periods, respectively) compared to the two-dose clotrimazole regimen (76.0%, 61.6%, and 59.8%, all P < 0.05). The three-dose fluconazole regimen showed no significant difference to three-dose clotrimazole regimen, with cure rates of 82.8%, 79.3%, and 75.9% (all P > 0.05). The two-dose fluconazole regimen had cure rates of 74.3%, 56.4% and 51.1%, with no significant difference from two-dose clotrimazole regimen at days 7–14 and 25–35, but lower than three-dose fluconazole regimen at days 25–35 and 35 to 6 months. The three-dose clotrimazole regimen demonstrated higher cure rates in Candida albicans and non-albicans Candida SVVC cases than two-dose regimen. These findings suggest that three-dose antifungal regimens may be more efficacious than two-dose regimens for SVVC. The three-dose clotrimazole regimen could serve as a promising alternative for SVVC management.

Shining a light on Candida-induced epithelial damage with a luciferase reporter.

Host cell damage is a key parameter for research in infection biology, drug testing, and substance safety screening. In this study, we introduce a luciferase reporter system as a new and reliable assay to measure cell damage and validate it with the pathogenic yeast, Candida albicans, as a test case. We transduced human epithelial cell lines with a lentiviral vector to stably express an optimized luciferase enzyme, Nanoluc. Upon cell damage, the release of cytoplasmic luciferase into the extracellular space can be easily detected by a luminometer. We used the luciferase reporter system to investigate the damage caused by C. albicans to different newly generated epithelial reporter cell lines. We found that fungus-induced cell damage, as determined by established methods, correlated tightly with the release of the luciferase. The new luciferase reporter system is a simple, sensitive, robust, and inexpensive method for measuring host cell damage and has a sensitivity comparable to the standard assay, release of lactate dehydrogenase. It is suitable for high-throughput studies of pathogenesis mechanisms of any microbe, for antimicrobial drug screening, and many other applications.IMPORTANCEWe present a quick, easy, inexpensive, and reliable assay to measure damage to mammalian cells. To this end, we created reporter cell lines which artificially express luciferase, an enzyme that can be easily detected in the supernatant when these cells are damaged. We used infections with the well-investigated fungal pathogen of humans, Candida albicans, as a test case of our system. Using our reporter, we were able to recapitulate the known effects of strain variability, gene deletions, and antifungal treatments on host cell damage. This easily adaptable reporter system can be used to screen for damage in infection models with different microbial species, assay cell-damaging potential of substances, discover new non-toxic antibiotics, and many other damage-based applications.

Effectiveness of Antifungal Treatment for Onychomycosis

Onychomycosis is a prevalent fungal infection of the nails, which causes thickening, discoloration, and detachment of the nail bed. The condition is mainly caused by various fungal species, including dermatophytes, yeasts and molds. Treatment of onychomycosis is complex, with antifungal drugs playing a key role. This research aimed to evaluate the effectiveness of various antifungal treatments, both topical and systemic, in managing onychomycosis. This research used a descriptive qualitative approach, using secondary data through documentation analysis. Data were triangulated to increase reliability and validity. The findings showed that the effectiveness of antifungal treatment varied depending on the type of drug, duration of treatment, and patient compliance. Systemic antifungals, such as terbinafine and itraconazole, showed higher cure rates compared to topical treatments such as ciclopirox and amorolfine. However, all treatments had high relapse rates, underscoring the need for continuous monitoring and customized therapy. The implications of this research demonstrate the importance of personalized treatment plans and the development of strategies to prevent relapse, which remains a significant challenge in the management of onychomycosis.

Fungal Shoulder Periprosthetic Infections: A Systematic Review.

Background: Data regarding fungal PJIs of the shoulder are scarce. The present systematic review aims to identify and evaluate all published shoulder fungal PJIs in an effort to better understand the diagnostic and therapeutic approach to these infections. Methods: A systematic review according to the PRISMA guidelines was conducted, locating all shoulder fungal PJIs. The initial search located 1435 articles. Data were collected on demographics, the causative fungus, antifungal treatment (AFT), surgical interventions, and infection outcomes. Results: After screening and implementation of the inclusion criteria, a total of 10 articles, including 10 cases, were eligible. The sample's mean age was 62.44 years. Diabetes mellitus was the most common comorbidity (30%), while 70% were immunocompromised. Candida spp. was the most common causative fungus (nine cases; 90%), while all cases were confirmed with cultures. In three cases (30%), there was bacterial co-infection. The mean duration of antifungal treatment (AFT) was 8.4 weeks, while the preferred agent was fluconazole (60% of cases), followed by amphotericin B (30%). Most cases (50%) underwent resection arthroplasty as part of the treatment, while two-stage revision arthroplasty was performed in 30%. Infection's eradication was reported in 90% of the studied cases. Conclusions: The diagnosis and management of fungal periprosthetic shoulder infections are particularly challenging and require a multidisciplinary approach. The combination of antifungal therapy and tailored surgical strategies is crucial, but further research is needed to refine treatment protocols and address the unique considerations in shoulder PJIs.

Pregnancy-related intracranial venous sinus thrombosis secondary to cryptococcal meningoencephalitis: a case report and literature review

BackgroundCerebral venous sinus thrombosis (CVST), a serious cerebrovascular and neurological emergency, is common in pregnant individuals and accounts for approximately 0.5–1.0% of all cerebrovascular diseases. However, CVST with cryptococcal meningoencephalitis in immunocompetent pregnant patients is rare.Case presentationA 30-year-old woman who was 33 weeks pregnant presented with recurrent dizziness, headache, and vomiting as the main clinical manifestations, all of which were initially nonspecific. After assessment of the cerebrospinal fluid, skull computerized tomography, magnetic resonance imaging, and other laboratory and imaging examinations, the patient was diagnosed with secondary pregnancy-related CVST with cryptococcal meningoencephalitis. Despite receiving potent anticoagulant and antifungal treatment, the patient’s condition deteriorated, and the patient’s family opted to cease treatment.ConclusionsWe present a rare case of CVST with cryptococcal meningoencephalitis in an immunocompetent pregnant patient. The difficulty of diagnosing and treating secondary pregnancy-related CVST caused by cryptococcal meningoencephalitis, as well as the great challenges faced at present are highlighted. One crucial lesson from the present case is that when clinical and imaging signs are unusual for CVST during pregnancy, it is essential to account for the possibility of other central nervous system (CNS) diseases, such as CNS infections with Cryptococcus, which may cause CVST.

Invasive Fungal Disease in Pediatric Heart Transplant Recipients

Abstract Background The epidemiology of IFD following pediatric heart transplantation (pHT) is poorly characterized. We sought to evaluate use of antifungal prophylaxis and describe the epidemiology of IFD in pHT at two large children’s hospitals. Methods We performed a retrospective cohort study of pediatric and young adult (≤21 years) patients undergoing heart transplantation at Cincinnati Children’s Hospital Medical Center (CCHMC) and Children’s Hospital of Philadelphia (CHOP) between 2012 and 2021. We recorded demographic, clinical, medication, and laboratory data for pHT patients through 12 months post-transplant. We identified use of topical (oral nystatin) and systemic antifungal prophylaxes in the peri-transplant period (7 days prior through 14 days following transplant) and analyzed if certain transplant variables were associated with the administration of systemic antifungals during this period using rank sum and chi squared tests. Applying published definitions, we quantified the incidence of proven and probable IFD and explored the characteristics of these cases. Results A total of 201 patients underwent heart transplant at CCHMC and CHOP. The majority were male (60.2%), White (66.7%), and not Hispanic or Latino (88.1%). Median age at time of transplant was 7.4 years (IQR 0.9-14.2). During the peri-transplant period, 143 (71.1%) patients received oral nystatin and 37 (18.4%) received systemic antifungal prophylaxis, not including PJP prophylaxis. 41 individuals (20.4%) were not on any antifungal prophylaxis throughout this period. Delayed chest closure was significantly associated with the administration of systemic antifungals (p&amp;lt;0.001) while several other variables (age, hospital, immunosuppression medication, ECMO/LVAD pre-transplant) were not. In total, 8 patients (4%) developed proven (n=5) or probable (n=3) IFD. In our cohort, the incidence rate of proven/probable IFD in the first year post-transplant was 44.8 per 1000 patient-years. The characteristics of these cases are shown in Table 1. Time from pHT to IFD ranged from 11 days to 196 days (median time = 25.5 days). All cases of proven IFD occurred within 28 days of transplant. In three cases of proven/probable IFD, patients were receiving a systemic antifungal or PJP prophylaxis in the seven days prior to IFD onset. Two cases met the definition of probable IFD but the infections resolved without directed therapies. Four patients with proven IFD died within 1 year following transplant, although in only 3 cases was IFD a contributing factor. The one-year all-cause mortality rate among pHT patients with proven/probable IFD (50%) was higher than that in pHT patients without IFD (10.3%; Fisher’s exact p=0.008). Conclusion Over a 10-year period at CCHMC and CHOP, 4% of pHT patients developed proven or probable IFD within one-year post-transplant. All proven IFD cases occurred within a month of transplant while probable cases occurred more than 100 days post-transplant. Delayed chest closure was significantly associated with the administration of systemic antifungal prophylaxis. Patients with proven IFD had poor outcomes despite receipt of appropriate antifungal treatment. Given the low incidence of IFD at these two centers, we were unable to evaluate risk factors for IFD in this population and so larger studies would be needed.

Clinical insights into Invasive Aspergillosis in Mexican children with cancer

Abstract Background In the last years Invasive Aspergillosis (IA) has become the most frequent invasive fungal infection (IFI) affecting children with hematological malignancies. This complication results in the delay of cancer treatment and/or poor prognosis mainly due to late diagnosis and late start of antifungal treatment. Therefore, antifungal prophylaxis and preemptive approaches have been proposed for these patients based on risk factors and local epidemiological data. For this reason, we performed a unicenter, descriptive and prospective study to determine the frequency and clinical course of IA in hospitalized cancer patients with fever and neutropenia. Methods we included events of fever and neutropenia of hospitalized patients with cancer and either with persistent febrile neutropenia (PFN: fever for &amp;gt;96h with total neutrophil count of &amp;lt;500cells/mm3) or profound prolonged neutropenia (PPN: total neutrophil count of &amp;lt;500cells/mm3 for &amp;gt;7 days). Informed consent was requested prior inclusion and follow up of these events was performed with weekly measurement of serum galactomannan antigen (until the recovery of neutrophil count), lung computed tomography (CT) and/or sinus and/or central nervous system (CNS) imaging, depending on clinical findings, and if feasible bronchoscopy to obtain bronchioalveolar lavage (BAL) samples. Clinical and laboratory data were obtained; with this information diagnosis of IA was classified as possible, probable, and proven, according to the EORTC/MSG guidelines. This protocol was approved by the hospital’s research and ethics committees (INP 041/2021). For data analysis categorical variables were presented as frequencies and numerical variables as median and range. Statistical analysis was made with X2 and U Mann Whitney tests. Results Seventy events were included, 14 (20%) had IA diagnosis; 2 possible, 11 probable and 1 proved. Median of age was 10.2y (5.5 – 17) and 64.3% were male. Acute lymphoblastic leukemia was the main oncologic diagnosis (71.4%), 35.7% during induction phase; followed by acute myeloblastic leukemia (21.4%). 92.9% of events with IA presented as PFN (p=0.001) with a fever duration of 3.5 days (1-8) (p=0.004). Pulmonary disease was evident in all events with IA, two had disseminated infection. In 5/14 events serum galactomannan antigen was positive in the first measurement. Only 8 events underwent bronchoscopy: BAL was positive in 6 and 4 had positive culture with Aspergillus spp. Lung CT scan showed different findings, lobar/segmental consolidation and nodule with halo sign were the most common; 85.7% of cases presented with more than one radiological sign (p=0.003). Voriconazole monotherapy was given to 78.5% of IA cases and 21.4% required combined antifungal therapy (added caspofungine or liposomal amphotericin B) due to disseminated disease or severe clinical course. Intensive care admission resulted with statistical significance for the events with diagnosis of IA (64.3% p= 0.019). Within the IA events survival at 60 days was of 78.6%. Conclusion Frequency of IA was high among our high risk cancer patients. This study demonstrates the importance of a complete work up for invasive fungal infection in high-risk patients with persistent febrile neutropenia. The information obtained is of great use for the implementation of pre-emptive approaches and antifungal prophylaxis in this patient population.

Chronic Disseminated Candidiasis among Pediatric Cancer Patients: The Hidden Threat

Abstract Background Chronic disseminated Candidiasis (CDC) is a severe invasive fungal infection observed during neutrophil recovery in patients with acute leukemia treated with intensive chemotherapy. Clinical manifestations include persistent fever under broad-spectrum antibiotics and abdominal discomfort. HSC is characterized by the presence of nodular lesions in the liver, spleen, and other organs (lungs, kidneys, and skin) on radiological imaging. Methods The retrospective study was conducted from 2013 - 2022 including all pediatric hematological patients diagnosed with chronic disseminated candidiasis admitted and treated in Children’s Cancer Hospital Egypt (CCHE). Data included primary diagnosis, clinical presentation, microbiological, radiological, and treatment data. Results Three hundred fifty (350) pediatric cancer patients were diagnosed with candidemia. The median age was four years (4 months- 18 years). Chronic dissemination candidiasis (CDC) was reported in 30(9%) of our patients. The most affected organs were Liver (19 patients), spleen (13), renal (13), cautelous (13), brain (2) and retina (2). Candida tropicalis was the most common isolated spp. from blood/tissue culture (24 patients) followed by C. parapsilosis (3 patients). The primary diagnosis in patients with CDC was ALL (24 Patients) while (4 patients) has AML. CDC was developed on top of antifungal prophylaxis in 7 patients (24%): liposomal-amho B (3 patients), Micafungin (3 patients) and voriconazole (1 patient). Candida tropicalis was the most common isolated spp. from blood/tissue culture (80%). Steroid as treatment for CDC immune reconstitution syndrome done in around 50% of patients (Persistent fever with neutrophil recovery, absent progressive clinical/radiological findings). PET-CT was done in 10 patients with positive uptake in all cases, was helpful in resuming intensive chemotherapy in six patients despite persistent lesions in CT and was used to stop antifungal treatment despite positive radiological lesions in CT in three patients. The first line of treatment was echinocandin (53%) and liposomal ampho-B (46%) with overall mortality among CDC patients were 30%. Conclusion CDC is still a hidden threat among pediatric patients with still high mortality rate. Antifungal stewardship through screening and Rapid diagnosis using non-culture diagnostics are needed. PET scan is a helpful tool for diagnosis and response assessment and can add to treatment decision. Figure 1. Chronic Disseminated Candidiasis among Pediatric Cancer patients.

Identifying gaps in the international consensus case definitions for invasive aspergillosis (IA): a review of clinical cases not meeting these definitions

Abstract Background International consensus-definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically-significant cases are often excluded from clinical studies for not meeting proven/probable IA case-definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 of such cases, for their clinical, microbiological characteristics and outcomes. Methods Data on 47 cases not meeting consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. Clinical, microbiological, radiological characteristics of these cases were analysed. Mortality outcomes were compared with those of 221 proven/probable cases. Results Of 47 cases studied, 15 lacked classical host-factors, 22 exhibited only single positive Aspergillus PCR result, 7 lacked typical IA radiological findings on chest computed tomography, 3 had borderline galactomannan optical density indices (&amp;lt;1.0 but ≥0.5) in bronchoalveolar lavage fluid. Median age of patients was 61 years (IQR 52-68); 34 were males (72%). Seven patients (15%) required intensive-care admission. All patients had lung as primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to 30% mortality in the comparative cohort (n=221). Conclusion Our findings highlight the limitations of current consensus-definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to those with proven/probable IA. Further studies, especially of patients with single positive Aspergillus PCR and those without host-factors, are needed to determine if future consensus-definitions may benefit from modifications.

Angioinvasive Rhino-Orbital-Cerebral Mucormycosis in a Patient with Type 2 Diabetes Mellitus: A Complex and Lethal Cause of Stroke

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales, particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient’s condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases.

Azole Combinations and Multi-Targeting Drugs That Synergistically Inhibit Candidozyma auris.

Limited antifungal treatment options and drug resistance require innovative approaches to effectively combat fungal infections. Combination therapy is a promising strategy that addresses these pressing issues by concurrently targeting multiple cellular sites. The drug targets usually selected for combination therapy are from different cellular pathways with the goals of increasing treatment options and reducing development of resistance. However, some circumstances can prevent the implementation of combination therapy in clinical practice. These could include the increased risk of adverse effects, drug interactions, and even the promotion of drug resistance. Furthermore, robust clinical evidence supporting the superiority of combination therapy over monotherapy is limited and underscores the need for further research. Despite these challenges, synergies detected with different antifungal classes, such as the azoles and echinocandins, suggest that treatment strategies can be optimized by better understanding the underlying mechanisms. This review provides an overview of multi-targeting combination strategies with a primary focus on Candidozyma auris infections.

7183 Histoplasmosis Of Adrenal In An Immunocompetent Patient From Arizona: A Surprising Biopsy

Abstract Disclosure: R. Habibi: None. S. Penquite: None. N. Ebrahimi: None. R. Cardenas Lara: None. Introduction: Histoplasmosis of adrenal gland in the context of disseminated infection is a rare entity in a non-endemic area. Early diagnosis and treatment can save one’s life. Here we present a case of a patient from Arizona who was referred to us with a large adrenal mass initially resembling malignancy. Presentation: A 58-year-old male with no significant medical history from Bisbee Arizona presented to our clinic with significant weight loss of 120 pounds in 8months, jaundice, fatigue, nausea and vague abdominal pain. He had an abdominal CT scan in a rural area hospital which showed a left adrenal 4.2 x 4.3 x 3.7 cm mass with average HU=40, with interval development from a CT scan 6months prior to that which showed left adrenal 1.5 x 1.3 x 1.3 cm mass. He had the initial CT scan after a mechanical fall. He was experiencing sweating, dizziness and low blood pressure of 90/60 mmhg, but used to have hypertension. Physical examination revealed diffuse jaundice in an ill appearing cachectic individual. Laboratory data were significant for total bilirubin of 4.9, direct bilirubin 0.7. Plasma metanephrines and normetanephrines, 24-hour urine free cortisol, morning cortisol levels and DHEA sulfate were normal. Other findings on the CT scans of head, chest and abdomen were soft tissue thickening between the right posterior 10th and 11th ribs along with hepatosplenomegaly, nodular lung lesions with calcified granuloma, sub centimeter brain lesions within the left putamen/external capsule junction with corresponding mild edema. During the following month after initial visit he developed bilateral tongue masses with dysphagia along with enlarging bilateral adrenal lesions, measuring up to 4.4 cm on the right and 5.2 cm on the left. The patient was admitted to hospital for further extensive work up. He underwent biopsies of left adrenal mass and tongue lesions which demonstrated necrotizing granulomatous inflammation with fungal elements compatible with histoplasmosis. Liposomal amphotericin B was started, which was quickly switched to itraconazole 200mg twice a day once lumbar puncture result was normal. His transient low blood pressures resolved. He was seen in clinic after few weeks with overall improving symptoms. Follow up with imaging of adrenal in few months is planned. He is currently in his third month of treatment for histoplasmosis with itraconazole. Discussion: The presentation of disseminated histoplasmosis can resemble malignancy as illustrated in this case. Southwest of the United States is an unusual geographical area for such infection. Initial unilateral involvement of adrenal as a mass in an immunocompetent individual is also uncommon. Considering dramatic response to antifungal treatment, a clinician should suspect such rare infections when seeing a nonfunctional adrenal mass with rapidly progressive constitutional symptoms. Presentation: 6/3/2024

Optimizing Water, Temperature, and Density Conditions for In Vitro Pea (Pisum sativum L.) Germination.

This study aimed to determine the optimal water, temperature, and density conditions, alongside antifungal treatments, for pea (Pisum sativum L.) germination in a laboratory setting, with implications for research, breeding, and microgreen production. Germination and early seedling growth were assessed across various temperatures (5 °C to 40 °C), water levels (0-14 mL per Petri dish), seed densities (5, 7, 9, and 11 seeds per Petri dish), and antifungal treatments (Hypo and Bordeaux mixture). The results indicated that optimal germination occurred between 15 °C and 25 °C, with peak performance at 25 °C. Water levels between 7 and 11 mL per 9 cm diameter Petri dish supported robust root and shoot development, while minimal water levels initiated germination but did not sustain growth. Five seeds per Petri dish was optimal for healthy development, whereas higher densities led to increased competition and variable outcomes. Antifungal treatments showed slight improvements in germination and growth, though differences were not statistically significant compared to controls. The study's novelty lies in its holistic approach to evaluating multiple factors affecting pea germination, offering practical guidelines for enhancing germination rates and seedling vigor. These findings support efficient and resilient crop production systems adaptable to varying environmental conditions, contributing to sustainable agriculture and food security. Future research should explore these factors in field settings and across different pea cultivars to validate and refine the recommendations.

Invasive Candidiasis in Pediatric Hematologic Malignancy: Increased Risk of Dissemination With Candida tropicalis.

Candida species are the most common cause of invasive fungal disease, and children with hematologic malignancy are at increased risk. Non-albicans Candida (NAC) now account for more than half of all invasive candidiasis (IC) and carry a worse prognosis. We aimed to compare the epidemiology, risk factors, organ dissemination, biomarkers and outcomes in IC based on the species implicated and evaluate trends in antifungal resistance over time. Patients 0-18 years of age with hematologic malignancy and IC at 2 centers were included. Fifty-three patients from 2011 to 2022 were identified. Information related to demographics, host and risk factors, Candida species and antifungal susceptibilities, treatment and outcomes was collected via retrospective chart review. Data were analyzed at the species level. The incidence rate of IC was 29 per 1000 patients with leukemia and lymphoma. The median time to infection from diagnosis of malignancy was 38 days. Candida tropicalis (n = 17; 30%) was the most identified species followed by Candida albicans (n = 14; 25%). Patients with C. tropicalis infection were more likely to have dissemination to the eyes (P = 0.035), spleen (P = 0.001) and skin (P = 0.003) than patients with C. albicans or other NAC. Of the 34 patients who underwent dilated retinal examination, 24% (n = 8) had evidence of intraocular candidiasis. Seven of the 8 patients with intraocular disease had prolonged candidemia (3 or more days; P = 0.003). The 12-week crude mortality rate was 16.9%. NAC, specifically C. tropicalis, accounted for most of the IC in children with hematological malignancies. Screening for intraocular candidiasis continues to play an important role in patients with IC, and future studies are needed to determine if screening can be limited to patients with select risk factors.

Phytotherapy as an alternative approach in oral candidiasis management: A systematic review protocol

Background Conventional antifungal therapies, including topical applications, are effective against oral candidiasis but have limitations such as resistance development and cytotoxicity especially for immunocompromised patients. Phytotherapy presents a promising alternative, offering potential solutions to these challenges. However, despite numerous clinical trials, there is a lack of standardized protocols for phytotherapeutic applications. This systematic review protocol seeks to evaluate the potential of phytotherapy as an alternative treatment for oral candidiasis and compare its efficacy with standard antifungal therapies. Protocol This protocol aims to assess the effectiveness of phytotherapy compared to standard antifungal treatments for oral candidiasis. Initially, controlled descriptors in MeSH terms (e.g., “Candidiasis, Oral,” “Phytotherapy”) and keywords were selected from MEDLINE and combined using Boolean operators (‘AND’, ‘OR’) to create a comprehensive search strategy. Titles and abstracts will be screened by two independent reviewers to select studies that meet the inclusion criteria. The quality and risk of bias of the selected studies will be assessed afterward. Data will be gathered using standardized tools and subsequently synthesized for analysis. Discrepancies between reviewers will be settled through discussion, or, if required, by involving a third reviewer. Discussion Results obtained from this systematic review will describe various natural compounds like essential oils, herbal extracts, and bioactive plant ingredients that exhibit antifungal properties used against oral candidiasis and will evaluate their effectiveness in comparison to standard antifungal treatments. Systematic review registration PROSPERO: CRD42024584029 (Registered on 07/09/2024)

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.