Evolutionary trends in antifungal resistance: a meta-analysis.

The present paper includes a meta-analysis of literature data on 318 species of fungi belonging to 34 orders in their response to 8 antifungal agents (amphotericin B, caspofungin, fluconazole, itraconazole, ketoconazole, posaconazole, terbinafine, and voriconazole). Main trends of MIC results at the ordinal level were visualized. European Committee on Antimicrobial Susceptibility Testing and Clinical & Laboratory Standards Institute (CLSI) clinical breakpoints were used as the staff gauge to evaluate MIC values ranging from resistance to susceptibility, which were subsequently compared with a phylogenetic tree of the fungal kingdom. Several orders (Hypocreales, Microascales, and Mucorales) invariably showed resistance. Also the basidiomycetous orders Agaricales, Polyporales, Sporidiales, Tremellales, and Trichosporonales showed relatively high degrees of azole multi-resistance, while elsewhere in the fungal kingdom, including orders with numerous pathogenic and opportunistic species, that is, Onygenales, Chaetothyiales, Sordariales, and Malasseziales, in general were susceptible to azoles. In most cases, resistance vs susceptibility was consistently associated with phylogenetic distance, members of the same order showing similar behavior. IMPORTANCE: A kingdom-wide the largest set of published wild-type antifungal data comparison were analyzed. Trends in resistance in taxonomic groups (monophyletic clades) can be compared with the phylogeny of the fungal kingdom, eventual relationships between fungus-drug interaction and evolution can be described.

Fusariosis in burn patients: A systematic review of case reports.

Burns can cause skin damage, facilitating the entry of fungi and other microorganisms into the body, leading to infections. Fusarium is a fungus capable of infecting individuals with burn injuries. Diagnosing and treating Fusarium infections in burn patients can be challenging due to the manifestation of nonspecific symptoms. This study aims to investigate case reports and case series from published literature describing Fusarium infection in burned patients, in order to assess treatment regimens, clinical outcomes, and make recommendations for future management. We conducted searches on Web of Science, PubMed, ScienceDirect, and Medline for all case reports and case series containing keywords 'Burn', 'Burns', 'Burned', 'Fusarium', or 'Fusariosis' in the title or abstract. All burn patients who developed Fusarium fungal infections between January 1974 and March 2023 were included in the study. Demographic and clinical data were analyzed retrospectivity. The final analysis incorporates 24 case reports encompassing a total of 87 burn patients with Fusarium infection. Patient ages ranged from one to 85 years, with the majority being male (53%). The median percentage of burn surface area was 78%, and the skin in the face, upper limbs, and lower limbs were the most commonly infected sites. Fungal infections appeared around 10 days after the burn injury on average. The majority of the patients were identified through culture or histopathology. The Fusarium dimerum species complex, which was found in nine patients, was the most frequently identified Fusarium species complex. Amphotericin B was the most preferred treatment drug, followed by voriconazole, and 62% of patients underwent debridement. In our study, 23 patients (37%) died from fungal infections. Implementing early and effective treatment protocols targeting Fusarium spp. in burn treatment units can significantly reduce mortality rates. It is critical to enhance the understanding of fusariosis epidemiology and emphasize the importance of maintaining a high clinical suspicion for this condition in burn patients.

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%.

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.

Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae.

Several prolonged and significant outbreaks of dermatophytosis caused by Trichophyton indotineae, a new emerging terbinafine-resistant species, have been ongoing in India in recent years, and have since spread to various countries outside Asia. Miltefosine, an alkylphosphocholine, is the most recently approved drug for the treatment of both visceral and cutaneous leishmaniasis. Miltefosine in vitro activity against terbinafine-resistant and susceptible T. mentagrophytes/T. interdigitale species complex, including T. indotineae, is limited. The current study aimed to assess miltefosine's in vitro activity against dermatophyte isolates, which are the most common causes of dermatophytosis. Miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole susceptibility testing was performed using Clinical and Laboratory Standards Institute broth microdilution methods (CLSI M38-A3) against 40 terbinafine-resistant T. indotineae isolates and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale species complex isolates. Miltefosine had MIC ranges of 0.063-0.5 µg/mL and 0.125-0.25 µg/mL against both terbinafine-resistant and susceptible isolates. In terbinafine-resistant isolates, the MIC50 and MIC90 were 0.125 µg/mL and 0.25 µg/mL, respectively, and 0.25 µg/mL in susceptible isolates. Miltefosine had statistically significant differences in MIC results when compared to other antifungal agents (p-value 0.05) in terbinafine-resistant strains. Accordingly, the findings suggest that miltefosine has a potential activity for treating infections caused by terbinafine-resistant T. indotineae. However, further studies are needed to determine how well this in vitro activity translates into in vivo efficacy.

Antifungal activity of miltefosine against both azole-susceptible and -resistant Aspergillus strains.

Miltefosine, an alkylphosphocholine, has been approved recently for the treatment of visceral leishmaniasis. Miltefosine has shown promise as a treatment for paracoccidioidomycosis, and has mixed activity against other fungi and yeast. There are limited data on the in-vitro activity of miltefosine against azole-resistant and -susceptible Aspergillus spp. As such, the aim of this study was to determine the in-vitro activity of miltefosine against Aspergillus strains. Miltefosine was tested against 108 azole-susceptible and -resistant Aspergillus strains isolated from Iran and other countries using the broth microdilution method. Miltefosine was found to be effective against azole-resistant Aspergillus isolates, with minimum inhibitory concentrations (MICs) ranging from 1.562 to 6.25 µg/mL. MIC50 and MIC90 were 1.562 and 3.125 µg/mL, respectively. Miltefosine had a higher geometric mean MIC (2.459 µg/mL) for wild-type Aspergillus isolates than itraconazole (0.220 µg/mL) and voriconazole (0.298 µg/mL). No significant difference was found between miltefosine MICs for azole-resistant Aspergillus isolates and azole-susceptible Aspergillus isolates (P>0.05). Miltefosine appears to have good in-vitro activity against azole-resistant Aspergillus strains, according to these findings. Furthermore, the findings suggest that miltefosine could be used to treat infections caused by azole-resistant Aspergillus spp.

Otomycosis: The foremost aetiological agent causing otitis externa and the antifungal susceptibility pattern in North-Western Iran.

BACKGROUND: Otomycosis is considered a recurring fungal ear infection. The external auditory canal provides an appropriate and optimal situation for fungal growth. OBJECTIVES: The study aimed to identify the causative agents of otomycosis and determine corresponding antifungal drug susceptibility patterns in north-western Iran. METHODS: From October 2020 until November 2021, 200 patients attended an otolaryngology referral centre with otitis externa, and their ear discharge and debris were examined and cultured. The identification of the fungal agents was implemented by polymerase chain reaction-restriction fragment length polymorphism and sequencing. In vitro antifungal susceptibility testing of the isolates was conducted in accordance with the CLSI broth microdilution protocols. RESULTS: The prevalence of otomycosis was measured 50.5% (n = 101/200). The majority of patients were in their forties (n = 35, 34.6%) and female (n = 57, 56.4%), and the most prevalent symptom was otalgia (56.4%). The most underlying factor was remarked manipulation employing a cotton swab (65.3%). Regarding fungus, Aspergillus section Nigri (58.57%) was the foremost isolate, followed by Aspergillus section Flavi (19.23%) and Candida parapsilosis (14.96%). The predominance of Aspergillus isolates had minimal in vitro sensitivity to tioconazole and nystatin. Candida species represented higher geometric mean minimum inhibitory concentrations (MIC) against nystatin. The MIC of three Aspergillus species isolates shown above the epidemiologic cut-off values (ECV) against itraconazole. CONCLUSIONS: Otomycosis incidence surpassed in comparison with the previous study as the most common cause of otitis externa. The MIC distribution of Aspergillus species isolates against triazole antifungals is close to the defined ECVs and likely outrun it over time.

Invasive fungal infections in children with leukemia in a tertiary hospital in Oman: An eight-year review.

Background and Purpose: Invasive fungal disease (IFD) is a common and serious consequence of leukemia in children and the incidence of these infections has increased due to chemotherapy. This study aimed to present the epidemiology of IFD in a cohort of children with leukemia from a tertiary reference institution in Oman. Materials and Methods: A retrospective study of IFDs in pediatric patients below 13 years of age with newly diagnosed or relapsed leukemia was conducted at the Royal Hospital in Muscat, Oman. From 2010 to 2017, IFD episodes in children with leukemia were evaluated retrospectively, considering age, gender, type of leukemia, chemotherapy regimen, IFD detection phase, neutropenia, prevention, diagnostic method, and treatment. Results: Between 2010 and 2017, 198 children with leukemia were admitted and treated at Royal Hospital. Invasive fungal infection (IFI) was diagnosed in 32 patients out of 198 (16.1%), and IFI was defined as probable and proven in 53% (n=17) and 47% (n=15) of the cases, respectively. At 1.1:1, the male-to-female ratio was roughly equal. According to chest computed tomography scans, 65.6% of patients had radiological features of fungal infections. Positive fungal cultures were found in the bronchoalveolar lavage of three patients, 37.5% of whom had positive blood cultures, and 3% had positive urine cultures as a neonatal invasive candidiasis. In three patients, invasive aspergillosis caused pulmonary IFD, accounting for 9.3% of all infection sites. Candidaemia was found in 28% of IFD patients, and the most common organism was Candida tropicalis (15.6%), followed by Candida parapsilosis (6.25%). Furthermore, the major risk factor was febrile neutropenia. Conclusion: In children with leukemia, invasive fungal infection is common and serious. Despite aggressive treatment, mortality among these high-risk patients remains high.

Actinomortierella wolfii: Identity and pathology.

Actinomortierella wolfii (Mortierellales), formerly Mortierella wolfii, is a causative agent of bovine systemic infection and abortion. Human infections caused by this species are extremely rare. Here, we present a case of a patient with B-Cell Acute Lymphoblastic Leukemia (B-ALL) who was diagnosed with a rhinocerebral infection caused by this fungus. Amphotericin treatment of the patient proved unsuccessful. This type of disease is otherwise nearly exclusively limited to members of the order Mucorales. The taxonomy of the causative agent is discussed.

Ten decadal advances in fungal biology leading towards human well-being.

Fungi are an understudied resource possessing huge potential for developing products that can greatly improve human well-being. In the current paper, we highlight some important discoveries and developments in applied mycology and interdisciplinary Life Science research. These examples concern recently introduced drugs for the treatment of infections and neurological diseases; application of -OMICS techniques and genetic tools in medical mycology and the regulation of mycotoxin production; as well as some highlights of mushroom cultivaton in Asia. Examples for new diagnostic tools in medical mycology and the exploitation of new candidates for therapeutic drugs, are also given. In addition, two entries illustrating the latest developments in the use of fungi for biodegradation and fungal biomaterial production are provided. Some other areas where there have been and/or will be significant developments are also included. It is our hope that this paper will help realise the importance of fungi as a potential industrial resource and see the next two decades bring forward many new fungal and fungus-derived products.

Detection of emerging genotypes in Trichophyton mentagrophytes species complex: A proposal for handling biodiversity in dermatophytes.

A resistant and hypervirulent dermatophyte from India has been described as a taxonomic novelty, Trichophyton indotineae, a species of the Trichophyton mentagrophytes complex. Rapid detection and correct identification of closely similar dermatophytes with different predilections are essential for efficient clinical management. We evaluated the efficacy of rapid diagnostic methods clinical and environmental strains in the T. mentagrophytes complex. The methods included Real-time-PCR, DermaGenius, LAMP, and MALDI-ToF MS, using rDNA ITS sequences as taxonomic standard. The results show that only MALDI-ToF MS can distinguish 96.97% T. indotineae from other closely related species. The complex comprises numerous clones which may differ in anonymous markers but with similar evolutionary behavior. Therefore, we recommend to distinguish species only when they show an appreciable degree of adaptation and thus are clinically significant. The distinction of remaining clonal diversity is an epidemiological query and can be solved by haplotype numbering.

In Vitro Antifungal Susceptibility Profile of Miltefosine against a Collection of Azole and Echinocandins Resistant Fusarium Strains.

Fusarium species are filamentous fungi that cause a variety of infections in humans. Because they are commonly resistant to many antifungal drugs currently available in clinical settings, research into alternative targets in fungal cells and therapeutic approaches is required. The antifungal activity of miltefosine and four comparators, amphotericin B, voriconazole, itraconazole, and caspofungin, were tested in vitro against a collection of susceptible and resistant clinical (n = 68) and environmental (n = 42) Fusarium isolates. Amphotericin B (0.8 µg/mL) had the lowest geometric mean (GM) MICs/MECs values followed by miltefosine (1.44 µg/mL), voriconazole (2.15 µg/mL), caspofungin (7.23 µg/mL), and itraconazole (14.19 µg/mL). Miltefosine was the most effective agent against Fusarium isolates after amphotericin B indicating that miltefosine has the potential to be studied as a novel treatment for Fusarium infections.

Initial Results of the International Efforts in Screening New Agents against Candida auris.

BACKGROUND: Candida auris is an emergent fungal pathogen and a global concern, mostly due to its resistance to many currently available antifungal drugs. OBJECTIVE: Thus, in response to this challenge, we evaluated the in vitro activity of potential new drugs, diphenyl diselenide (PhSe)2 and nikkomycin Z (nikZ), alone and in association with currently available antifungals (azoles, echinocandins, and polyenes) against Candida auris. METHODS: Clinical isolates of C. auris were tested in vitro. (PhSe)2 and nikZ activities were tested alone and in combination with amphotericin B, fluconazole, or the echinocandins, micafungin and caspofungin. RESULTS: (PhSe)2 alone was unable to inhibit C. auris, and antagonism or indifferent effects were observed in the combination of this compound with the antifungals tested. NikZ appeared not active alone either, but frequently acted cooperatively with conventional antifungals. CONCLUSION: Our data show that (PhSe)2 appears to not have a good potential to be a candidate in the development of new drugs to treat C. auris, but that nikZ is worthy of further study.

Onychomycosis Caused by Fusarium Species.

Onychomycosis is a nail fungal infection that produces nail discolouration, thickness, and separation from the nail bed. The species of the Fusarium genus that cause onychomycosis are emerging and the number of cases has increased throughout the years. Microscopic examination, as well as cultures, are required for the accurate diagnosis of onychomycosis. The goal of treatment is to eliminate the organism that causes the disease and restore the nail's normal appearance. Here, we provide an overview of the onychomycosis cases that have been reported in literature over the last 24 years, which have been caused by the Fusarium species. We performed a review on the onychomycosis cases caused by the Fusarium species from January 1997 to January 2021. Patients aged between 40 and 49 years made up 30.23% of the cases. The most common aetiologic species was Fusarium solani species complex (FSSC), which accounted for 44.11% of the cases, followed by F. fujikuroi species complex (FFSC), which accounted for 17.64%; 14.70% of the cases were due to F. dimerum species complex (FDSC) and 14.70% of the cases were due F. oxysporum species complex (FOSC). Europe accounted for 29.06% of the cases caused by FOSC, whereas Africa accounted for 46.67% of the cases due to FSSC. The clinical presentation of onychomycosis due to Fusarium spp. is commonly the distal-lateral pattern of onychomycosis. Identification of the infectious agent in onychomycosis cases due to Fusarium is crucial in deciding the proper treatment. Although antifungal susceptibility tests have only been performed in a few cases, susceptibility testing can help with patient management.

Evaluation of Candida colonization index, molecular identification, and antifungal susceptibility pattern of Candida species isolated from critically ill pediatric patients: A single-center study in Iran.

Background and Purpose: Given the high mortality rate of invasive candidiasis in hospitalized pediatric patients, it is crucial to establish a predictive system to achieve early diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated from pediatric patients with high Candida colonization index (CI). Materials and Methods: This study was carried out at the Children's Medical Center in Tehran-Iran. In total, 661 samples were collected from 83 patients. The Candida CI was calculated according to the descriptions of previous studies. The isolates were identified using polymerase chain reaction-based techniques. The Clinical and Laboratory Standard Institute protocol M60 was used to conduct the antifungal susceptibility test. Results: A colonization index greater than 0.5 was confirmed in 29 cases (58% of positive samples) with two children developing candidemia. Candida albicans (n=53, 49.5%) was the most common Candida species in patients with CI > 0.5. Except for acute lymphoblastic leukemia, no risk factors were linked to a high index in colonized children (P > 0.05). Twelve isolates (7.01%) were multi-azole resistant with high MICs against both isavuconazole and ravuconazole and seven strains (4.09%) were echinocandins resistant. Conclusion: In pediatric intensive care units, patients are at risk of fungal infection, particularly candidemia. In this study, more than half of the children with positive yeast cultures had CI > 0.5, and 6.8% developed candidemia.

First Case of Subcutaneous Mycoses Caused by Dirkmeia churashimaensis and a Literature Review of Human Ustilaginales Infections.

Objective: Dirkmeia churashimaensis, belonging to Ustilaginales fungi, has never been reported as clinical pathogenic until very recently. In this study, we report an unusual subcutaneous infection with Dirkmeia churashimaensis and reviewed all human Ustilaginales infections. The aim is to better understand their epidemiology, infection type, risk factors, and the sensitivity to antifungal agents. Methods: An 80-year-old female farmer developed extensive plaques and nodules on her left arm within 2 years. Pathological and microbiological examinations identified a new pathological agent, Dirkmeia churashimaensis, as the cause of this infection. The patient was successfully cured by oral itraconazole. We reviewed a total of 31 cases of Ustilaginales cases, among of which only three were skin infections. Results: Local barrier damage (i.e., surgery, trauma, and basic dermatosis) and systemic immunodeficiency (i.e., preterm and low birthweight, Crohn's disease, malignant cancer, and chemotherapy) are risk factors for Ustilaginales infection. The D1/D2 and ITS regions are the frequently used loci for identifying the pathogens together with phenotype. Most patients could survive due to antifungal treatment, whereas seven patients died. Amphotericin B, posaconazole, itraconazole, and voriconazole showed good activity against these reported strains, whereas fluconazole, 5-flucytosine, and echinocandins usually showed low susceptibility. Itraconazole had good efficiency for subcutaneous infections. Conclusions: The present case study and literature review reveal that Ustilaginales can be opportunistic pathogenic normally in immunocompromised and barrier damage people. A proper identification of fungi can be crucial for clinical treatment, and more data of antifungal are needed for choice of medication against this kind of infections.

Molecular Mechanisms of 5-Fluorocytosine Resistance in Yeasts and Filamentous Fungi.

Effective management and treatment of fungal diseases is hampered by poor diagnosis, limited options for antifungal therapy, and the emergence of antifungal drug resistance. An understanding of molecular mechanisms contributing to resistance is essential to optimize the efficacy of currently available antifungals. In this perspective, one of the oldest antifungals, 5-fluorocytosine (5-FC), has been the focus of recent studies applying advanced genomic and transcriptomic techniques to decipher the order of events at the molecular level that lead to resistance. These studies have highlighted the complexity of resistance and provided new insights that are reviewed in the present paper.

Antifungal Susceptibility of 182 Fusarium Species Isolates from 20 European Centers: Comparison between EUCAST and Gradient Concentration Strip Methods.

We determined the susceptibility of 182 Fusarium species isolates to five antifungal drugs (amphotericin B, voriconazole, posaconazole, isavuconazole, and terbinafine) by the EUCAST method. Based on the latest taxonomic insights, isolates collected from 20 European centers were distributed into seven complexes and 27 species. The susceptibility was variable, depending on the species. Comparison with the gradient concentration strip method, which was used for 77 isolates, showed essential agreement values for voriconazole, posaconazole, isavuconazole, and amphotericin B of 17%, 91%, 83%, and 70%, respectively.

Basidiobolus omanensis sp. nov. Causing Angioinvasive Abdominal Basidiobolomycosis.

Human infectious fungal diseases are increasing, despite improved hygienic conditions. We present a case of gastrointestinal basidiobolomycosis (GIB) in a 20-year-old male with a history of progressively worsening abdominal pain. The causative agent was identified as a novel Basidiobolus species. Validation of its novelty was established by analysis of the partial ribosomal operon of two isolates from different organs. Phylogeny of ITS and LSU rRNA showed that these isolates belonged to the genus Basidiobolus, positioned closely to B. heterosporus and B. minor. Morphological and physiological data supported the identity of the species, which was named Basidiobolus omanensis, with CBS 146281 as the holotype. The strains showed high minimum inhibitory concentrations (MICs) to fluconazole (>64 µg/mL), itraconazole and voriconazole (>16 µg/mL), anidulafungin and micafungin (>16 µg/mL), but had a low MIC to amphotericin B (1 µg/mL). The pathogenic role of B. omanensis in gastrointestinal disease is discussed. We highlight the crucial role of molecular identification of these rarely encountered opportunistic fungi.