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Background: Infections due to rare molds, such as Fusarium spp., cause severe and difficult-to-control diseases with increasing frequency. Data on fusariosis in children and on the use of voriconazole (VCZ), considered a drug of choice, are scarce in infants and children <2 years of age., Case Presentation: We present the first, to our knowledge, pediatric case of disseminated mycosis due to Fusarium musae in a 15-month-old boy with relapsed/refractory acute lymphoblastic leukemia, diagnostics and outcome. Herein, at this severely immunocompromised patient, after prompt diagnosis, disseminated fusariosis was successfully treated with high-dose VCZ at a final dose of 15 mg/kg of body weight twice a day. This occurred by achieving adequate drug exposures as determined by drug susceptibility testing and followed by therapeutic drug monitoring without observed toxicity., Conclusions: Appropriate diagnostic approach and timely administration of optimal antifungal therapy with VCZ were important for the successful treatment of disseminated fusariosis. Therapeutic drug monitoring, especially in <2-year-old children, is necessary to achieve sufficient drug exposure for optimal therapeutic response without toxicity., Competing Interests: Emmanuel Roilides received research grants from Merck, Abvie, Shionogi, Cidara and Pfizer, Inc, to his institution and is a scientific advisor and a member of the Speaker Bureau for Gilead, Merck, Shionogi, Mundipharma and Pfizer, Inc. The remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mycotic keratitis (MK) represents a corneal infection, with Fusarium species identified as the leading cause. Fusarium is a genus of filamentous fungi commonly found in soil and plants. While many Fusarium species are harmless, some can cause serious infections in humans and animals, particularly Fusarium keratitis, that can lead to severe ocular infections, prevalent cause of monocular blindness in tropical and subtropical regions of the world. Due to its incidence and importance in ophthalmology, we conducted a systematic analysis of clinical cases to increase our understanding of Fusarium keratitis by gathering clinical and demographic data., Methods: To conduct an analysis of Fusarium keratitis, we looked through the literature from the databases PubMed, Embase, Lilacs, and Google Scholar and found 99 papers that, between March 1969 and September 2023, corresponded to 163 cases of Fusarium keratitis., Results: Our analysis revealed the Fusarium solani species complex as the predominant isolate, with females disproportionately affected by Fusarium keratitis. Notably, contact lens usage emerged as a significant risk factor, implicated in nearly half of cases. Diagnosis primarily relied on culture, while treatment predominantly involved topical natamycin, amphotericin B, and/or voriconazole. Surprisingly, our findings demonstrated a prevalence of cases originating from the United States, suggesting potential underreporting and underestimation of this mycosis in tropical regions. This shows the imperative for heightened vigilance, particularly in underdeveloped regions with substantial agricultural activity, where Fusarium infections may be more prevalent than currently reported., Conclusion: Our study sheds light on the clinical complexities of Fusarium keratitis and emphasizes the need for further research and surveillance to effectively tackle this vision-threatening condition. Furthermore, a timely identification and early initiation of antifungal treatment appear to be as important as the choice of initial treatment itself., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Fungal keratitis due to Fusarium species is a rare but serious ocular disease. Due to its rapid progression, often late diagnostic confirmation as well as limited topical treatment options, this is potentially sight threatening. Increasing contact lens use and global climate change have been suggested to be factors leading to an increase in cases of fusarium keratitis, even in regions with moderate climate. Early recognition and initiation of antimycotic treatment, as well as early surgical treatment by penetrating keratoplasty are decisive for the outcome., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Infectious keratitis, a significant contributor to blindness, with fungal keratitis accounting for nearly half of cases, poses a formidable diagnostic and therapeutic challenge due to its delayed clinical presentation, prolonged culture times, and the limited availability of effective antifungal medications. Furthermore, infections caused by rare fungal strains warrant equal attention in the management of this condition., Case Presentation: A case of fungal keratitis was presented, where corneal scraping material culture yielded pink colonies. Lactophenol cotton blue staining revealed distinctive spore formation consistent with the Fusarium species. Further analysis using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) identified the causative agent as Fusarium proliferatum. However, definitive diagnosis of Pseudonectria foliicola infection was confirmed through ITS sequencing. The patient's recovery was achieved with a combination therapy of voriconazole eye drops and itraconazole systemic treatment., Conclusion: Pseudonectria foliicola is a plant pathogenic bacterium that has never been reported in human infections before. Therefore, ophthalmologists should consider Pseudonectria foliicola as a possible cause of fungal keratitis, as early identification and timely treatment can help improve vision in most eyes., (© 2024. The Author(s).)

Purpose of Review: Fusarium species are an increasingly important cause of meningitis and invasive disease in immunocompromised patients as well as in otherwise healthy patients as observed in two recent healthcare-associated outbreaks. This review summarizes recently published information on treatment and diagnosis of this infection., Recent Findings: Incidence of Fusarium species meningitis and invasive fusariosis are increasing. Molecular techniques are improving the speed of diagnosis. New antifungal agents in development show good in vitro activity against some Fusarium species. New technologies, including cerebrospinal fluid (CSF) filtration, may play a role in treatment of central nervous system (CNS) disease. Due to the continued prime importance of the host immune system in recovery, immunomodulatory treatments may play a role in treatment., Summary: The overall incidence of CNS fusariosis is increasing with a continued poor prognosis, but new diagnostic and treatment modalities are in development which may offer improvements., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023 Wiley-VCH GmbH. Published by John Wiley & Sons Ltd.)

Sea Turtle Egg Fusariosis (STEF) is a worldwide emergent fungal disease affecting eggs and causing embryos mortality in turtle's nests such as those of Caretta caretta. It is caused by a complex of species belonging to Fusarium genus, particularly those included in the Fusarium Solani Species Complex (FSSC). During the samplings carried out in summer 2020 along the Tuscany coastlines (Italy), C. caretta eggs showed clinical signs resembling those caused by STEF. A total of 32 fungal isolates were obtained from lesioned eggs whose molecular characterization allowing identifying as belonging to FSSC / Neocosmospora spp., Fusarium oxysporum Species Complex (FOSC) / F. oxysporum and Fusarium nodosum, i.e., fungal genera and speciesincluding also well-known plant pathogens. Isolates inoculated on several plant hosts did not result in any pathogenic activity but F. nodosum causing, on wheat spikes, disease symptoms.This is the first time F. nodosum has been isolated from portions of eggs showing evident signs of fungal infection. This work represents the first report of Fusarium spp. isolated from C. caretta eggs showing lesions resembling those caused by STEF on Tuscan coast thus posing a significant concern to loggerhead sea turtle conservation also in this region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

Invasive fungal rhinosinusitis (IFRS) is a life-threatening infection that can occur in immunocompromised patients, including those with COVID-19. Although Mucorales and Aspergillus species are the most common causes of IFRS, infections caused by other fungi such as Fusarium are rare. In this report, we present three cases of proven rhinosinusitis fusariosis that occurred during or after COVID-19 infection. The diagnosis was confirmed through microscopy, pathology, and culture, and species identification of the isolates was performed by DNA sequencing the entire ITS1-5.8 rRNA-ITS2 region and translation elongation factor 1-alpha (TEF-1α). Antifungal susceptibility testing was conducted according to CLSI guidelines. The causative agents were identified as Fusarium proliferatum, F. oxysporum + Aspergillus flavus , and F. solani/falciforme. Treatment involved the administration of antifungal medication and endoscopic sinus surgery to remove the affected mucosa, leading to the successful resolution of the infections. However, one patient experienced a recurrence of IFRS caused by A. flavus 15 months later. Early diagnosis and timely medical and surgical treatment are crucial in reducing mortality rates associated with invasive fusariosis. Additionally, the cautious use of corticosteroids in COVID-19 patients is highly recommended., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Erami, Aboutalebian, Hashemi Hezaveh, Matini, Momen-Heravi, Ahsaniarani, Arani, Ganjizadeh and Mirhendi.)

Purpose: Fusarium keratitis possesses significant diagnostic and therapeutic challenges. Medically relevant Fusaria belong to various species complexes and show prominent differences in their antifungal susceptibility profile which may influence the clinical outcome. Rapid diagnostic methods are warranted for precise identification of species complexes for prompt initiation of correct antifungals. The aim of the study was to compare between matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and polymerase chain reaction sequencing for correct species-level identification and to analyze the clinical outcome among different Fusarium species complexes., Methods: Twenty-nine culture-proven Fusarium keratitis cases were included in this study. A phylogenetic tree was constructed after TEF1α gene sequencing and isolates were subjected to MALDI-TOF MS, followed by database expansion and identification. Clinical outcome and risk association among species complexes were analyzed retrospectively., Results: Maximum likelihood phylogeny categorized 68.9% isolates as Fusarium solani species complex (FSSC), 17.2% as Fusarium dimerum species complex (FDSC), followed by 13.7% as Fusarium fujikuroi species complex (FFSC). With extended database, MALDI-TOF MS could correctly speciate 96.5% (28/29) isolates. Previous antibiotic usage ( P = 0.034) and preoperative antifungal treatment with natamycin, voriconazole, or ketoconazole ( P = 0.025) were significantly higher in the FSSC group. The patients in the FFSC group had a significantly longer duration of symptoms at the time of clinical presentation to the clinic (15 days vs. 5 days, P = 0.030). Among 11 patients with a clinically poor outcome, 9 (31%) had FSSC infection., Conclusions: Patients infected with the FSSC had more aggressive infection with poor prognosis. MALDI-TOF MS can serve as the best alternative method to conventional molecular identification with reduced turnaround time, which may help the ophthalmologists to consider the appropriate antifungals or early surgical intervention for improved outcome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce. The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

The outcome of invasive fusariosis in hematological patients is usually dismal, particularly in patients with persistent neutropenia. We report a patient with acute myeloid leukemia (AML) with Fusarium dimerum sinusitis with hematogenic dissemination to the brain. Despite surgical debridements of the sinuses and liposomal amphotericin B, voriconazole and terbinafine, there was progression with cerebral involvement after recovery of neutropenia and with detection of F. dimerum in the cerebrospinal fluid. Topical antifungal treatment with amphotericin B deoxycholate (deoxy-AMB) intrathecally was initiated with administration three times a week. After 99 treatments of intrathecal deoxy-AMB, she had regression of the fusarium CNS lesions and is currently in complete remission from AML. This report supports the use of intrathecal amphotericin B for treatment of CNS fusariosis., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Fusarium spp. can cause invasive infection with fatal outcomes in immunocompromised patients. Therefore, invasive fusariosis is rare after solid organ transplantation. For this reason, experience and management are limited to single published case reports.We report a 65-year-old female patient with disseminated brain abscesses caused by Fusarium after liver transplantation (LT). The patient underwent LT for secondary sclerosing cholangitis after acute respiratory distress syndrome (ARDS). After a complicated course with aneurysm and thrombosis of the hepatic artery, re-transplantation was performed after one month. Due to inadequate awakening response, cerebral imaging was performed, which showed multiple abscesses. The patient died shortly thereafter, and an autopsy showed fusariosis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Meningoencephalitis can be a diagnostic dilemma and one of its etiology are infectious causes including fungal agents. Fusarium species have attracted much attention as one of the invasive fungal infections. Major clinical manifestations of infections due to Fusarium spp. are broad such as keratitis, endophthalmitis, sino-pulmonary and central nervous system (CNS) infections. However, CNS fusariosis is rare and often happens due to hematogenous dissemination from other sites. Herein, we describe an unusual case of meningoencephalitis caused by Fusarium proliferatum, in a patient with rheumatoid arthritis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Fungal keratitis, an infective disease of the cornea, represents a serious diagnostic and therapeutic problem that, if not recognized on time, could lead to irreversible eye damage. Herein we report a case of fungal keratitis due to Fusarium spp. infection. The 60-year-old man was admitted to our clinic due to an atraumatic acute onset of the disease, with a decrease in the visual acuity, photophobia, redness, and severe pain in the right eye. Clinical observation revealed an ulcer that affected 1/3 of the cornea and a hypopion in the anterior chamber. After the first results of microbiological analyzes, local and systemic antifungal therapy was applied. Due to the fact that the patient voluntarily left the treatment, there was a drastic worsening of the local findings as a full thickness total corneal infiltrate with more intense anterior chamber reaction. Finally, evisceration was performed. Given the fact that fungal keratitis is more prevalent in developing countries, official protocols and available effective antifungals are crucial for adequate treatment and a favorable outcome of this infection., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Marija Trenkic, Gordana Stankovic Babic, Marina Randelovic, Miljan Krstic, Marija Radenkovic, Suzana Tasic-Otasevic.)

Purpose of Review: To investigate the peculiarities of invasive fusariosis (IF) in pediatric patients., Methods: We conducted a systematic literature review to identify human cases of locally invasive and systemic fusariosis documented in children (up to 18 years) published between 1973 (first case report) and 2021., Recent Findings: One hundred and six cases were retrieved, and hematologic malignancy was reported in 64% (68/106) of the cases. The most frequent anatomic sites involved were skin 66% (70/106), blood 47% (50/106), and lungs 35% (37/106), bone and joint (8%, 09/106), and eye/central nervous system involvement (8%, 9/106). Fusarium solani, followed by Fusarium oxysporum, were the most commonly reported species. In disseminated fusariosis, relapsed or refractory baseline disease (P < 0.001, OR=10.555, CI 95% 3.552-31.365) was associated with poor outcome, whereas voriconazole-based therapy was associated with better prognosis (P  = 0.04, OR = 0.273, CI 95% 0.076-0.978)., Summary: Hematologic malignancies and solid tumors requiring intensive immunosuppression are the main conditions related to IF in children where other organs than skin, blood, and lungs were frequently involved. Voriconazole therapy appears to be also effective in children with IF, despite the wide pharmacokinetic variability of this triazole in pediatric patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Invasive fusariosis is a serious infection affecting mostly patients with haematologic malignancies and hematopoietic cell transplant recipients., Objectives: To develop a scoring tool that evaluates guideline adherence in the management of invasive fusariosis., Methods: We reviewed two guidelines, provided by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and the European Confederation of Medical Mycology (ECMM), and selected the strongest recommendations for management quality as the bases for the scoring tool., Results: We reviewed the recommendations regarding primary and secondary prophylaxis, diagnostics procedures (images, blood cultures, biopsy of skin lesions with direct examination, culture and histopathology, species identification, antifungal susceptibility tests and antigen detection), treatment choices and follow-up procedures. The tool comprises 18 items, with a maximum of 24 points., Conclusions: The EQUAL score Fusariosis is a tool that may help clinicians to measure guidelines adherence., (© 2021 Wiley-VCH GmbH.)

Purpose: Fungal keratitis (FK) is a serious ophthalmic disease with a potentially devastating outcome that seems to be increasing in recent years. The use of contact lenses (CLs) was evaluated as a risk factor for FK to determine possible differences in course and outcome., Methods: Data from 173 cases reported in the German FK registry until August 2019 were evaluated regarding CL behavior, other ophthalmological and general risk factors, age, sex, identified pathogens, conservative and surgical therapy, visual acuity, and findings at admission and follow-up., Results: One hundred seventy-four eyes from 173 patients between 2000 and 2019 were included [64.4% women, median age 54 (39; 72) years]; 49.7% wore CL, of which 81.3% were soft CL, and 50.3% had no history of contact lens use (NCL). CL users were significantly more often women and otherwise healthy (CL: 80.2% vs. NCL: 48.9%; P < 0.0001). The spectrum of pathogens among CL users showed a significantly higher proportion of infections with filamentous pathogens, in particular Fusarium sp. (total filament: CL 69.8% vs. NCL 27.3%; P = 0.0001; Fusarium sp.: CL 50.0% vs. NCL 14.8%; P < 0.0001). Overall, 54.6% required keratoplasty and 8.6% enucleation., Conclusions: CLS are the most important risk factor for FK in Germany. With CLs, typically, the infection is caused by molds, and patients are comparably younger and otherwise healthy. Often, extensive surgery is needed. To evaluate changes in the pathogen and resistance spectrum and to further monitor possible CL-related risk factors, a consistent collection of data remains paramount., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Watermelon is an important commercial crop in the Southeastern United States and around the world. However, production is significantly limited by biotic factors including fusarium wilt caused by the hemibiotrophic fungus Fusarium oxysporum forma specialis niveum (Fon). Unfortunately, this disease has increased significantly in its presence over the last several decades as races have emerged which can overcome the available commercial resistance. Management strategies include rotation, improved crop resistance, and chemical control, but early and accurate diagnostics are required for appropriate management. Accurate diagnostics require molecular and genomic strategies due to the near identical genomic sequences of the various races. Bioassays exist for evaluating both the pathogenicity and virulence of an isolate but are limited by the time and resources required. Molecular strategies are still imperfect but greatly reduce the time to complete the diagnosis. This article presents the current state of the research surrounding races, both how races have been detected and diagnosed in the past and future prospects for improving the system of differentiation. Additionally, the available Fon genomes were analyzed using a strategy previously described in separate formae speciales avirulence gene association studies in Fusarium oxysporum races.

Background: Filamentous fungi are ubiquitous in plants, water, and soil. The predominant fungi that infect the human cornea include Fusarium and Aspergillus species. The onset of fungal endophthalmitis is indolent, and typically takes weeks to months to develop after corneal infection. We report a case of Fusarium infection complicating rheumatic keratitis that acutely progressed to endophthalmitis during intravenous tocilizumab therapy., Case Presentation: A 65-year-old female patient was referred to our department due to pain and decreased vision in her left eye. Slit-lamp examination showed a white focus on the upper peripheral cornea, hypopyon, anterior chamber fibrin formation, marked ciliary hyperemia, and whole corneal epithelial defects. As the corneal scraping smear was positive for filamentous fungi and Fusarium species were detected by aqueous humor polymerase chain reaction, anti-fungal therapy was started. Although the initial response to anti-fungal therapy was good, we observed corneal infiltration, worsening hypopyon, and vitreous opacity after tocilizumab infusion. Given that the infection continued to progress despite conservative therapy, we performed penetrating keratoplasty combined with vitrectomy. After removal of the white focus beneath the intraocular lens, a temporary corneal prosthesis was mounted and the dense vitreous opacity was removed. Finally, a frozen donor graft was sutured in place. The corneal infiltration, hypopyon, and vitreous opacity all disappeared after the operation., Conclusion: The rapid progression of Fusarium keratitis to endophthalmitis in a patient who was receiving a regular infusion of tocilizumab demonstrates that ocular condition should be closely monitored during systemic tocilizumab administration due to increased risk of infection.

Neocosmospora pseudensiformis (formerly Fusarium pseudensiforme) is a hyaline mold in the Fusarium solani species complex that has been changed to the genus Neocosmospora. Invasive fusariosis is a rare fungal infection in solid organ transplantation. The most commonly reported manifestation of invasive fusariosis in this setting is localized cutaneous fusariosis. Here, we present the first case report of isolated N pseudensiformis pulmonary infection in a patient with non-alcoholic steatohepatitis cirrhosis who underwent orthotopic liver transplantation. A 67-year-old Thai woman developed acute graft rejection, dyspnea, and pulmonary consolidation 6 months after liver transplantation. N pseudensiformis was isolated from her sputum, and her clinical symptoms were improved with voriconazole treatment. However, she succumbed to Acinetobacter baumannii hospital-acquired pneumonia and acute coronary syndrome with cardiogenic shock after 10 days of treatment., (© 2020 Wiley Periodicals LLC.)

Purpose: To evaluate the usefulness of serial in vivo confocal microscopy (IVCM) examinations to measure hyphal density for monitoring the treatment success among patients with fungal keratitis, and to compare the hyphal diameter as well as branching angle as a way of differentiation between Aspergillus and Fusarium species observed in IVCM., Study Design: Prospective nonrandomized study., Patients and Methods: The study was conducted from February 2015 to September 2016. Hyphal diameter, density and branching angle measurements were performed using IVCM at admission and on a weekly basis for at least 2 weeks after the start of treatment., Results: During the period of study, 65 patients with culture-confirmed fungal keratitis were recruited. Of them, 40 were culture-positive for Fusarium spp. and 25 patients for Aspergillus spp. Before the start of treatment, the mean branching angle did not differ between the two species and the mean hyphal diameter was statistically higher for Aspergillus spp. (p = 0.029). Two weeks after the start of treatment, the mean hyphal diameter was statistically lower (p < 0.001) in the treatment failure group. Also the hyphal density significantly decreased with successful treatment (p < 0.05)., Conclusion: Decreasing hyphal density in serial IVCMs might be used as an indicator to predict the successful response of fungal ulcers to treatment. Branching angle is not different between Aspergillus and Fusarium keratitis. The mean hyphal diameter is significantly lower in the treatment failure group.

Fusariosis is the second most common mold infection after aspergillosis, and keratomycosis is the most encountered implantation infection. Here, we report a case of a 4-year-old Han Chinese girl presenting with an itchy mass on her right face of almost 2 years' duration. Direct smear of the lesion sample was positive for fungal hyphae. Biopsy of the lesion showed many fungal hyphae in the epidermis and dermis. The pathogen was identified as Fusarium lichenicola by molecular sequencing and phylogenetic analysis based on the TEF-1α gene. Whole-exome sequencing analysis using her peripheral blood revealed a heterozygous mutation in the STAT3 gene, which is related to autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). The lesion improved following treatment with i.v. and intralesional amphotericin B, oral voriconazole and topical luliconazole cream. To our knowledge, this is the second reported case of a special localized cutaneous lesion caused by Fusarium species in a child with AD-HIES. Both cases suggest that STAT3 deficiency may increase susceptibility to fusariosis., (© 2019 Japanese Dermatological Association.)

Introduction: Onychomycosis is a debilitating, difficult-to-treat nail fungal infection with increasing prevalence worldwide. The main etiological agents are dermatophytes, which are common causative pathogens in superficial fungal mycoses. Conventional detection methods such as fungal culture have low sensitivity and specificity and are time-consuming. Aim: The main objective of this study was to design, develop and validate a real-time probe-based multiplex qPCR assay for the detection of dermatophytes and Fusarium species. Methodology: The performance characteristics of the qPCR assays were evaluated. The multiplex qPCR assays targeted four genes (assay 1:  pan-dermatophytes /Fusarium spp.; assay 2: Trichophyton rubrum/Microsporum spp.). Analytical validation was accomplished using 150 fungal isolates and clinical validation was done on 204 nail specimens. The performance parameters were compared against the gold standard (fungal culture) and expanded gold standard (culture in conjunction with sequencing). Results: Both the single-plex and multiplex qPCR assays performed well especially when compared against the expanded gold standard. Among the 204 tested nail specimens, the culture method showed that 125 (61.3 %) were infected with at least one organism, of which 40 yielded positive results for dermatophytes and Fusarium spp. These target organisms detected include 20 dermatophytes and 22 Fusarium spp. The developed qPCR assays demonstrated excellent limit of detection, efficiency, coefficient of determination, analytical and clinical sensitivity and specificity. Conclusion: The multiplex qPCR assays were reliable for the diagnosis of onychomycosis, with shorter turn-around time as compared to culture method. This aids in the planning of treatment strategies to achieve optimal therapeutic outcome.

Invasive fusariosis (IF) usually presents with high fungal burden at diagnosis, and this may contribute to its high mortality rate. The use 1,3-beta-D-glucan (BDG) may help to establish the diagnosis at an earlier disease stage and to monitor treatment. To evaluate the performance of BDG in the diagnosis of IF and its kinetics in relation to the outcome, we retrospectively tested serum samples of 13 cases of IF, analysed the temporal relationship between the first positive BDG test and the date of the diagnosis of IF, and the kinetics of BDG in relation to patients' outcome. We selected 13 controls with similar underlying diseases as cases, at least two serum samples stored, and no invasive fungal disease. Twelve patients with IF had at least one positive BDG (median 4, range 1-16). The test was positive before the diagnosis of IF in 11 of the 12 patients (91.6%), at a median of 10 days (range 1-32). The median BDG value increased (from 109 to 316 pg/mL, P = 0.04) in patients who died by day 30, and did not change significantly (99-101 pg/mL, P = 0.60) in survivors. Using two consecutive BDG tests, sensitivity, specificity, and positive and negative predictive values were 85%, 69%, 7% and 99%, respectively. BDG is positive in the majority of patients with IF, usually before the diagnosis, but the low positive predictive value limits its use to diagnose IF earlier. Once therapy is started, decreasing BDG values suggests treatment response., (© 2019 Blackwell Verlag GmbH.)

Superficial mycoses are commonly reported in captive pinnipeds, usually maintained in wet and warm environments, favorable to fungal growth. Most superficial mycoses in pinnipeds have been described as difficult to treat; however, the majority of the reports come from past decades. Cutaneous lesions associated with opportunistic Fusarium sp. infections have been previously recognized in this taxon. We described the clinical signs, associated lesions and diagnosis (thermography, imprint cytology, histopathology, culture, electron microscopy, PCR) of a fusariosis case by Fusarium sp. in the nails and skin of an adult male captive South American sea lion (Otaria flavescens) recently transferred from another zoological institution, and its successful long-term treatment with Ketoconazole PO (60 days) and Miconazole solution spray TO, followed by Itraconazole PO (30 days). Herein we provide a successful approach to the diagnosis and treatment of fusariosis.

A peptidogalactomannan (PGM) from Fusarium oxysporum was structurally characterized by a combination of chemical and spectroscopic methods, including one and two-dimensional nuclear magnetic resonance (1D and 2D NMR). The galactomannan component consists of a main chain containing (1→6)-linked β-D-galactofuranose residues with side chains containing (1→2)-linked α-D-Glcp, (1→2)-linked -β-D-Manp (1→2) and β-D-Manp terminal nonreducing end units and differs from that of Aspergillus fumigatus and Cladosporium resinae that present a main chain containing (1→6)-linked α-D-Manp residues presenting β-D-Galf as side chains of 3-4 units that are (1→5)-interlinked. The importance of the carbohydrate moiety of the F. oxysporum PGM was demonstrated. Periodate oxidation abolished much of the PGM antigenic activity. A strong decrease in reactivity was also observed with de-O-glycosylated PGM. In addition, de-O-glycosylated PGM was not able to inhibit F. oxysporum phagocytosis, suggesting that macrophages recognize and internalize F. oxysporum via PGM. F. oxysporum PGM triggered TNF-α release by macrophages. Chemical removal of O-linked oligosaccharides from PGM led to a significant increase of TNF-α cytokine levels, suggesting that their removal could exposure another PGM motifs able to induce a higher secretion of TNF-α levels. Interestingly, F. oxysporum conidia, intact and de-O-linked PGM were not able to induce IL-10 cytokine release. The difference in patient serum reativity using a PGM from F. oxysporum characterized in the present study as compared with a PGM from C. resinae, that presents the same epitopes recognized by serum from patients with aspergillosis, could be considered a potential diagnostic antigen and should be tested with more sera.

Since 2017, the nomenclature of Fusarium, Acremonium and Sarocladium species have changed, as these morphologically homogeneous, but phylogenetically heterogeneous species and species complexes may be differentiated using MALDI-TOF MS examination, analyzing nucleotic sequences. This resulted in taxonomical changes. We summarize the clinical course, diagnostic and therapeutic options of keratitis caused by Fusarium and Sarocladium. The challenge of Fusarium and Sarocladium keratitis management for an ophthalmologist lies in delayed diagnosis and therapy, fulminant progression and penetration of the Descemet's membrane, restricted availability, poor penetration of antifungal agents and therapy resistance. The diagnosis is based on the clinical history of corneal trauma or contact lens wear, PCR and MALDI-TOF MS, confocal microscopic examination, microbiological culture and light-microscopic analysis of corneal scrapings. As primary conservative treatment, 5% natamycin eye drops have to be used and with results of an antimycogram, topical 1% voriconazole or 0.15-0.25% amphotericin B, in some cases 0.02% polyhexamethylene-biguanide (PHMB) may be applied. Fusarium keratitis may benefit from additional 2 × 200 mg oral voriconazole treatment, daily. In therapy resistant cases, early, large diameter penetrating keratoplasty (PKP) has to be performed, with complete removal of the infected area. With late diagnosis, delayed specific treatment and surgery, mycotic hyphae may penetrate the Descemet's membrane, leading to the loss of vision and enucleation in about every fourth patient. In our paper, we also present the heterogeneous clinical history of five Fusarium and Sarocladium keratitis cases. Orv Hetil. 2019; 160(1): 2-11.

Fusarium species have emerged as responsible for a broad spectrum of infections, including superficial, locally invasive and disseminated ones, especially in the hospital environment. Since there are few reports of invasive and disseminated fusariosis in children, the aim of this study was to report four cases of nosocomial infection caused by this microorganism in children with cancer hospitalized in a public children's hospital located in Brazil. Two of these patients were female and two were male. All patients presented febrile neutropenia, while three patients had acute lymphocytic leukemia and one patient had Wilms' tumor as underlying disease. In two cases, fungi were isolated from blood and identified as Fusarium oxysporum species complex after phenotypic and genotypic studies, while in two other cases fungi were isolated from skin biopsies and identified as Fusarium solani species complex. One patient died 12 days after the onset of cutaneous lesions. All isolates, after susceptibility testing, presented high levels of minimum inhibitory concentration for itraconazole, voriconazole and amphotericin B. Considering the emergence of filamentous fungi as etiologic agents of nosocomial infections, health professionals should be aware of the problems these infections, especially fungal ones, may cause to debilitated patients.

Safflower wilt, caused by Fusarium oxysporum f. sp. carthami (Foc) is a major limiting factor for safflower (Carthamus tinctorius) production worldwide. In India alone, about 40-80% disease incidence has been reported. A rapid, efficient, specific, and sensitive diagnostic technique for Foc is therefore crucial to manage Fusarium wilt of safflower. Twenty-five isolates of F. oxysporum formae speciales infecting other crops, 17 isolates of Fusarium spp. and seven isolates of other fungal pathogens of safflower along with 75 Foc isolates were used for identification of band specific to Foc using inter-simple sequence repeat (ISSR) analysis. Out of 70 ISSR primers, the one that specifically amplified a 490 bp fragment from all the Foc isolates was selected. Sequence of the amplified fragment was utilized to design sequence characterized amplified region (SCAR) primers (FocScF/FocScR). The primer pair unambiguously and exclusively amplified a DNA fragment of approximately 213 bp in all the 75 Foc isolates. The primer set was able to detect as low as 10 pg of Foc genomic DNA using conventional PCR, while the SCAR primers when coupled with real-time qPCR demonstrated detection limits of 1 pg for Foc genomic DNA and 1000 conidia/g for soil. The assay enabled reliable diagnosis of Foc DNA in contaminated safflower fields and expedited Foc detection at 72 h post inoculation in asymptomatic seedlings. This method facilitates quick and precise detection of Foc in plant and soil samples and can be exploited for timely surveillance and sustainable management of the disease.

Owing to a lack of appropriate diagnostic and therapeutic approaches for mycotic keratitis, approximately one million cases of preventable corneal blindness are reported each year. The number of keratitis cases due to infection with Fusarium is increasing significantly worldwide, many of which are not treated adequately and in a timely manner due to frequent misdiagnosis. In the current report, we describe three cases of keratitis caused by Fusarium solani sensu stricto (FSSC5) from Turkey and The Netherlands, following ocular trauma. The etiological agent of keratitis, FSSC5, identified by sequencing of the partial tef1-α gene, exhibited low minimum inhibitory concentrations (MICs) of 1 µg/mL for amphotericin B and high MICs above the published epidemiological cutoff values for voriconazole (8 µg/mL). Patients were successfully treated with topical amphotericin B and voriconazole with complete recovery.