Low toxicity contributes to Sporothrix globosa invade the skin of patients in low-epidemic areas of China.

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.

Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae.

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

Comparison of the antifungal activity of the pyrimidine analogs flucytosine and carmofur against human-pathogenic dematiaceous fungi.

Chromoblastomycosis (CBM) and pheohyphomycosis (PHM) are the most common implantation mycoses caused by dematiaceous fungi. In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.

Fusarium falciforme eumycetoma: a diagnostic challenge of a neglected tropical disease.

Eumycetoma, a subcutaneous infection caused by various fungi with pathognomonic discharging grain, is rarely reported in Malaysia. This case concerns a eumycetoma infection in an immunocompetent man who presented with progressive left foot swelling complicated with pustules, sinuses and pale grain discharge for the past year after recurrent thorn pricks. Histological findings of the grain and tissue showed foci of septate fungal hyphae. Tissue culture yielded no growth. Amplification and sequencing of the rDNA internal transcribed spacer 1 (ITS1), ITS4 and large subunit regions of the tissue identified the causative agent as Fusarium falciforme, highlighting the role of molecular diagnostic method in identifying fungal species in eumycetoma. The patient was treated with surgical excision and oral itraconazole with excellent improvement. However, he presented again with recurrence after defaulting therapy. F. falciforme has been implicated in causing diseases in crops and sea turtles. Therefore, the One Health approach should be adopted to manage this emerging species.

Nodular lesions of the buttock for 20 years: the challenge of chromoblastomycosis in non-endemic settings.

Chromoblastomycosis is an implantation mycosis of the skin caused by certain species of melanised fungi. A man in his 50s, born in Kerala but living in England for 14 years, presented with a nodular lesion on his left buttock, which had been present for 20 years. Biopsy revealed muriform cells and fungal culture isolated Fonsecaea spp, consistent with a diagnosis of chromoblastomycosis. Treatment with oral terbinafine was initiated and changed to itraconazole based on results of antifungal susceptibility. Drug intolerance and low drug levels of itraconazole necessitated change to voriconazole and topical terbinafine. Despite long-term combined therapy, the lesions worsened, and the patient opted for surgical excision abroad. Recurrence was evident at surgical sites and combined therapy continues. Chromoblastomycosis is an insidious and burdensome neglected tropical disease. Within non-endemic countries, diagnosis remains challenging. A travel history and appropriate fungal investigations are vital.

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

BACKGROUND: The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. METHODS: An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. RESULTS: We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. CONCLUSION: We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Epistaxis and Facial Swelling Due to Nasal Blastomycosis in a Cat.

A 5 yr old castrated male domestic longhair was examined because of left-sided facial swelling and epistaxis. Head computed tomography with contrast identified a mass within the left nasal cavity and multifocal regions of nasal bone osteolysis. Histopathology of nasal mass biopsies and cytology of the facial swelling revealed pyogranulomatous inflammation due to Blastomyces dermatitidis. The cat experienced resolution of clinical signs following 8 mo of treatment with itraconazole. Although rare, clinicians should include blastomycosis on the differential diagnoses list of infectious causes for feline nasal disease if within an endemic area.

Itraconazole inhibits tumor growth via CEBPB-mediated glycolysis in colorectal cancer.

Advanced colorectal cancer (CRC) is characterized by a high recurrence and metastasis rate, which is the primary cause of patient mortality. Unfortunately, effective anti-cancer drugs for CRC are still lacking in clinical practice. We screened FDA-approved drugs by utilizing targeted organoid sequencing data and found that the antifungal drug itraconazole had a potential therapeutic effect on CRC tumors. However, the effect and mechanism of itraconazole on CRC tumors have not been investigated. A cell line-derived xenograft model in tumor-bearing mice was established and single-cell RNA sequencing was performed on tumor samples from four mice with or without itraconazole treatment. The proportion of cell populations and gene expression profiles was significantly different between the two groups. We found that itraconazole could inhibit tumor growth and glycolysis. We revealed that CEBPB was a new target for itraconazole, and that silencing CEBPB could repress CRC glycolysis and tumor growth by inhibiting ENO1 expression. Clinical analysis showed that CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival. In summary, itraconazole treatment remodeled cell composition and gene expression profiles. Itraconazole inhibited cell glycolysis and tumor growth via the CEBPB-ENO1 axis. In this study, we illustrate a new energy metabolism mechanism for itraconazole on tumor growth in CRC that will provide a theoretical basis for CRC targeting/combination therapy.

Itraconazole halts hepatocellular carcinoma progression by modulating sonic hedgehog signaling in rats: A novel therapeutic approach.

Liver cancer stands as the fourth leading global cause of death, and its prognosis remains grim due to the limited effectiveness of current medical interventions. Among the various pathways implicated in the development of hepatocellular carcinoma (HCC), the hedgehog signaling pathway has emerged as a crucial player. Itraconazole, a relatively safe and cost-effective antifungal medication, has gained attention for its potential as an anticancer agent. Its primary mode of action involves inhibiting the hedgehog pathway, yet its impact on HCC has not been elucidated. The main objective of this study was to investigate the effect of itraconazole on diethylnitrosamine-induced early-stage HCC in rats. Our findings revealed that itraconazole exhibited a multifaceted arsenal against HCC by downregulating the expression of key components of the hedgehog pathway, shh, smoothened (SMO), and GLI family zinc finger 1 (GLI1), and GLI2. Additionally, itraconazole extended survival and improved liver tissue structure, attributed mainly to its inhibitory effects on hedgehog signaling. Besides, itraconazole demonstrated a regulatory effect on Notch1, and Wnt/ß-catenin signaling molecules. Consequently, itraconazole displayed diverse anticancer properties, including anti-inflammatory, antiangiogenic, antiproliferative, and apoptotic effects, as well as the potential to induce autophagy. Moreover, itraconazole exhibited a promise to impede the transformation of epithelial cells into a more mesenchymal-like phenotype. Overall, this study emphasizes the significance of targeting the hedgehog pathway with itraconazole as a promising avenue for further exploration in clinical studies related to HCC treatment.

Disseminated Basidiobolomycosis Caused by Basidiobolus omanensis in a Child with Acute Lymphoblastic Leukemia (ALL). Case Report and Literature Review.

Basidiobolomycosis is an uncommon fungal infection caused by the genus Basidiobolus. In immunocompetent children, it usually causes cutaneous infection and rarely affects the gastrointestinal tract, and it is extremely rare for the disease to spread. The present study reports the first case of disseminated basidiobolomycosis caused by Basidiobolus omanensis in a child with acute lymphoblastic leukemia who died as a result of uncontrolled infection and multi-organ failure despite surgical and antifungal therapy with L-AMB and voriconazole. A review of the literature yielded 76 cases, including the current case with the majority of which were reported as invasive gastrointestinal infection. The median age was 4 years (61 male and 15 female) and the majority of these children were from the Middle East (80%), specifically Saudi Arabia (45%). Most patients were treated with systemic antifungal agents (mostly itraconazole and amphotericin B). Surgical intervention was done in 25% of these patients and the death rate was 12%.

Thamnostylum piriforme, a novel etiological agent of superficial mycosis.

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.

The cost-utility analysis of antifungal prophylaxis for invasive fungal infections in acute myeloid leukaemia patients receiving chemotherapy: a study from a middle-income country.

BACKGROUND: Invasive fungal infections (IFIs) contribute to morbidity and mortality during acute myeloid leukaemia (AML) treatment. Without prophylaxis, IFI rate during AML treatment in Thailand is high and results in a high mortality rate and a prolonged hospital stay. AIM: To evaluate the cost-utility of antifungal therapy (AFT) prophylaxis during AML treatment. METHODS: We assessed the cost-utility of AFT available in Thailand, including posaconazole (solution), itraconazole (solution and capsule), and voriconazole. A hybrid model consisting of a decision tree and the Markov model was established. RESULTS: The costs to prevent overall IFI using any AFT were all lower than the treatment cost of a non-prophylaxis group, resulting in a saving of 808-1507 USD per patient. Prevention with voriconazole prophylaxis showed the highest quality-adjusted life years (QALYs = 3.51, incremental QALYs = 0.23), followed by posaconazole (QALYs = 3.46, incremental QALY = 0.18) and itraconazole solution (QALYs = 3.45, incremental QALYs = 0.17). Itraconazole capsule reduced QALY in the model. For invasive aspergillosis prevention, posaconazole and voriconazole both resulted in better QALYs and life year savings compared with no prophylaxis. However, posaconazole prophylaxis was the only cost-saving option (976 USD per patient). CONCLUSION: Posaconazole, itraconazole solution and voriconazole were all cost saving compared with no prophylaxis for overall IFI prophylaxis, with voriconazole being the most cost-effective option. Posaconazole and voriconazole were both cost effective for invasive aspergillosis prevention but only posaconazole was cost saving. A change in reimbursement policy for the use of AFT prophylaxis during intensive AML treatment could provide both clinical benefits to patients and substantial economic benefits to healthcare systems.

Efficacy of topical trichloroacetic acid 100% either alone or combined with topical tioconazole 28% versus systemic itraconazole in the treatment of onychomycosis.

BACKGROUND: Treatment of onychomycosis is still challenging and warrants the development of new treatment strategies. Different trials were conducted to increase the penetration and efficacy of topical antifungals aiming at finding an alternative treatment especially when systemic antifungals are contraindicated. OBJECTIVES: To evaluate the efficacy of trichloroacetic acid (TCA) 100% either alone or combined with topical tioconazole 28% versus itraconazole pulse therapy in the treatment of onychomycosis. PATIENTS/METHODS: Forty-five patients with onychomycosis were divided into three groups: group (A) treated by topical TCA 100% for 12 sessions, group (B) treated by TCA 100% for 12 sessions combined with topical tioconazole 28% for 18 weeks and group (C) treated by itraconazole (400 mg/day for 1 week/month for 4 months). RESULTS: TCA 100% combined with topical tioconazole 28% showed the highest therapeutic response; however, the difference between the groups was statistically insignificant. Mycological cure (negative culture) was reported in 66.7% of group B versus 60% of group A and 40% of group C at the 20 week. CONCLUSIONS: TCA 100% is an effective and safe treatment option for onychomycosis especially when combined with antifungals. This modality is promising in the treatment of onychomycosis especially with the increased resistance to different antifungals.

Evaluation of the benefit of the addition of 1% topical luliconazole versus topical bland emollient to the systemic itraconazole therapy for the management of disseminated dermatophytosis: A randomised control trial.

BACKGROUND: The present epidemic of dermatophytosis in India is marked by an increase in chronic, recurrent and disseminated cases. A combination of oral itraconazole and topical luliconazole is being increasingly utilised by dermatologists in India. The superiority of this combination is not supported by robust clinical trial data. OBJECTIVE: We conducted this randomised, open-label, two arms, parallel assignment intervention trial between November 2022 and May 2023 to determine the superiority of topical 1% Luliconazole over bland emollient as adjuvant to systemic Itraconazole therapy in the management of dermatophytosis. METHOD: In this study, 135 patients of either sex were randomised to two study cohorts. Major exclusions being concomitant medical illness, use of concomitant medication and substance abuse. Participants were randomly assigned to receive topical bland emollient, (Cohort I, n = 67) or topical luliconazole, (Cohort II, n = 68). Both cohorts received oral itraconazole 200 mg/day (100 mg BID) and levocetirizine 5 mg twice a day as a systemic regime. Clinical and mycological cure at the end of 6 weeks and clinical relapse among cure patients during 10-week follow-up were observed. RESULTS: The cure rates for Cohorts I and II at 6 weeks were 50 (74.62%) and 56 (82.35%), (p = .46), respectively. During the 4-week follow-up period, clinical relapses were observed in 16 (32%) of the 50 patients in Cohort I and 12 (21.43%) of the 56 patients in Cohort II (p = .18). Luliconazole cohort shows a significantly higher medical cost (p < .05). CONCLUSION: Our study shows a similar cure rate and relapse rate for patients receiving topical Luliconazole versus topical bland emollient as an adjuvant to the systemic itraconazole regime.

Treatment of onychomycosis in an era of antifungal resistance: Role for antifungal stewardship and topical antifungal agents.

A growing body of literature has marked the emergence and spread of antifungal resistance among species of Trichophyton, the most prevalent cause of toenail and fingernail onychomycosis in the United States and Europe. We review published data on rates of oral antifungal resistance among Trichophyton species; causes of antifungal resistance and methods to counteract it; and in vitro data on the role of topical antifungals in the treatment of onychomycosis. Antifungal resistance among species of Trichophyton against terbinafine and itraconazole-the two most common oral treatments for onychomycosis and other superficial fungal infections caused by dermatophytes-has been detected around the globe. Fungal adaptations, patient characteristics (e.g., immunocompromised status; drug-drug interactions), and empirical diagnostic and treatment patterns may contribute to reduced antifungal efficacy and the development of antifungal resistance. Antifungal stewardship efforts aim to ensure proper antifungal use to limit antifungal resistance and improve clinical outcomes. In the treatment of onychomycosis, critical aspects of antifungal stewardship include proper identification of the fungal infection prior to initiation of treatment and improvements in physician and patient education. Topical ciclopirox, efinaconazole and tavaborole, delivered either alone or in combination with oral antifungals, have demonstrated efficacy in vitro against susceptible and/or resistant isolates of Trichophyton species, with low potential for development of antifungal resistance. Additional real-world long-term data are needed to monitor global rates of antifungal resistance and assess the efficacy of oral and topical antifungals, alone or in combination, in counteracting antifungal resistance in the treatment of onychomycosis.

Prolonged Itraconazole Therapy as Sole Treatment for Patients with Allergic Fungal Rhinosinusitis.

BACKGROUND: Currently, the mainstay of treatment for allergic fungal rhinosinusitis (AFRS) is surgical debridement along with topical or systemic steroids. However, prolonged systemic steroid therapy comes with side effects and is also sometimes contraindicated. Systemic antifungals have been used earlier as an adjunct to steroids or in refractory cases, but they have not been used as the sole primary treatment. OBJECTIVE: To study the effectiveness of sole Itraconazole therapy in patients with AFRS by comparison of clinical, radiological, and biochemical parameters before and after treatment. METHODS: Thirty-four patients diagnosed with localized sino-nasal AFRS were recruited and started on the tablet Itraconazole 200 mg orally twice daily for 3 months with q2weekly monitoring of liver function tests. The baseline clinical, radiological, and biochemical parameters were then compared with those after completion of 3 months of Itraconazole therapy. RESULTS: There was significant difference between all the parameters-clinical: SNOT-22 score (p < 0.001) and Meltzer endoscopy score (p < 0.001), radiological: Lund-Mackay score (p = 0.004) and 20-point CT score (p = 0.002), and biochemical: serum total IgE (p < 0.001), Aspergillus-specific IgE (p < 0.001), and absolute eosinophil count (p < 0.001). The clearance of the disease was more in anterior sinuses than the posterior ones. CONCLUSION: Prolonged Itraconazole can be given as sole therapy in AFRS, especially in patients for whom steroids are contraindicated or in those who are awaiting surgery. It can result in symptomatic and radiological improvement, but surgery still remains the definitive treatment option for AFRS for complete clearance of disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:545-551, 2024.

Hyperthermia is a promising potential adjunct to treating sporotrichosis: A refractory case of HIV sporotrichosis and in vitro experiments on Sporothrix spp.

BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.

A comprehensive review of nondermatophyte mould onychomycosis: Epidemiology, diagnosis and management.

Nondermatophyte moulds (NDMs) are widely distributed and can be detected in association with mycotic nails; however, sometimes it can be challenging to establish the role of NDMs in the pathogenesis of onychomycosis (i.e. causative vs. contaminant). In studies where the ongoing invasive presence of NDMs is confirmed through repeat cultures, the global prevalence of NDMs in onychomycosis patients is estimated at 6.9% with the 3 most common genus being: Aspergillus, Scopulariopsis and Fusarium. NDM onychomycosis can, in many cases, appear clinically indistinguishable from dermatophyte onychomycosis. Clinical features suggestive of NDMs include proximal subungual onychomycosis with paronychia associated with Aspergillus spp., Fusarium spp. and Scopulariopsis brevicaulis, as well as superficial white onychomycosis in a deep and diffused pattern associated with Aspergillus and Fusarium. Longitudinal streaks seen in patients with distal and lateral onychomycosis may serve as an additional indicator. For diagnosis, light microscopic examination should demonstrate fungal filaments consistent with an NDM with at least two independent isolations in the absence of a dermatophyte; the advent of molecular testing combined with histological assessment may serve as an alternative with improved sensitivity and turnover time. In most instances, antifungal susceptibility testing has limited value. Information on effective treatments for NDM onychomycosis is relatively scarce, unlike the situation in the study of dermatophyte onychomycosis. Terbinafine and itraconazole therapy (continuous and pulsed) appear effective to varying extents for treating onychomycosis caused by Aspergillus, Fusarium or Scopulariopsis. There is scant literature on oral treatments for Neoscytalidium.

Effect of Protein Corona on the Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections.

Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti-F4/80 and anti-MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.

Onychomycosis due to Fusarium species in different continents, literature review on diagnosis and treatment.

Fusarium species are an emerging cause of onychomycosis, and the number of cases has dramatically increased in recent decades worldwide. This review presents an overview of the onychomycosis cases caused by Fusarium species and diagnosis and treatment that have been reported in the literature. The most common causative agent of onychomycosis is F. solani species complex, which accounts for 11.68% of the cases of Fusarium onychomycosis, followed by the F. oxysporum species complex (164 out of 1669), which is accounted for 9.83% of the total. F. fujikuroi species complex (42 out of 1669) and F. dimerum species complex (7 out of 1669) are responsible for 2.52% and 0.42 cases, respectively. Fusarium nail infections were reported in patients aged range 1-98, accounting for 5.55% (1669 out of 30082) of all cases. Asia has the highest species diversity of Fusarium onychomycosis (31.51%). South America accounts for 21.09%, and the most common causative agent is F. solani (19.32%), followed by F. oxysporum species complex (15.63%). Europe accounts for 4.90% of cases caused by F. oxysporum, followed by F. solani. Africa accounts for 23.87% of the cases due to the F. solani species complex, followed by F. oxysporum and F. fujikuroi. Distal and lateral subungual onychomycosis was the most common clinical symptom accounting for 58.7% (135 out of 230) of the cases. Data analysis relieved that terbinafine and itraconazole are active treatments for Fusarium onychomycosis. For a definitive diagnosis, combining of direct examination, culture and sequencing of the elongation factor of translation 1α are recommended. Accurate identification of the causative agents of onychomycosis due to Fusarium species and antifungal susceptibility testing is essential in patient management.