Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

Species distribution and antifungal susceptibility profiles of clinical and environmental Fusarium isolates from Mexico: A multicenter study.

Fusarium spp. has emerged as an opportunistic etiological agent with clinical manifestations varying from localized infections to deep-seated systemic disease. It is also a phytopathogen of economic impact. There are few reports on the species diversity of this genus, and no comprehensive studies on the epidemiology nor the antifungal susceptibility of Fusarium in Mexico. The present multicentric study aims to shed light on the species distribution and antifungal susceptibility patterns of 116 strains of Fusarium isolated from clinical and environmental samples. Isolates were identified by standard phenotypic characteristics and by sequencing of the ITS (internal transcribed spacer), TEF1 (translation elongation factor 1-α), RPB2 (RNA polymerase II core subunit), and/or CAM1 (calmodulin) regions. Susceptibility tests were carried out against 15 antifungals of clinical and agricultural use. Regarding Fusarium distribution, we identified 27 species belonging to eight different species complexes. The most frequently isolated species for both clinical and environmental samples were F. falciforme (34%), F. oxysporum sensu stricto (12%), F. keratoplasticum (8%), and F. solani sensu stricto (8%). All Fusarium isolates showed minimum inhibitory concentrations (MICs) equal to or above the maximum concentration evaluated for fluconazole, 5-fluocytosine, caspofungin, micafungin, and anidulafungin. All isolates had a MIC of ≤16 µg/mL for voriconazole, with a mode of 4 µg/mL. F. verticillioides appeared to be the most susceptible to all antifungals tested.

Review Article White Piedra: Review of 131 cases.

This study analyzes the clinical characteristics of patients diagnosed with White Piedra through a systematic review of cases in the literature. A sample of 131 subjects was considered, of which 91.6% were female and most were 18 years of age or younger. Most studies were conducted in Brazil, followed by India, and Mexico. The most common etiologic agent found was Trichosporon spp (34.3%). Most affected patients were asymptomatic (94.6%) and predisposing factors included long hair, use of a hair band or hair accessories, and wet hair. The most common clinical feature was the presence of nodules. The evaluation of treatment effectiveness was hindered by the scarcity of follow-up information in the majority of the studies. It is concluded that White Piedra infection is more common in young women and is associated with hair-related factors.

Factors Associated with Candidiasis in Pemphigus Vulgaris Patients: Results from a Retrospective Study in Two Second-Care Level Hospitals in Mexico.

BACKGROUND: Infections are a major cause of morbidity and mortality in patients with pemphigus vulgaris (PV). One of the most common infections in these patients is candidiasis. This is probably due to the use of systemic immunosuppressants, including oral and intravenous corticosteroids, mainly in megadoses (pulse therapy), although it is unknown if there are other associated factors, in addition to immunosuppressive treatment. We determine the factors associated with candidiasis in PV patients in two second-care level hospitals in Mexico. METHODS: We reviewed 100 cases with PV. Cases were randomly selected from the databases of two second-care level hospitals between January 2010 and December 2019 (10 years). The primary endpoint was the incidence of candidiasis in patients with PV. RESULTS: One hundred patients with PV were enrolled in this retrospective study. Candidiasis was observed in 79 patients (79%). A maximum corticosteroid dose of 55 mg/day during the last year (p = 0.001) and a higher neutrophil/lymphocyte ratio were associated with candidiasis in patients with PV (p = 0.001). CONCLUSION: Risk factors favoring candidiasis in patients with PV are not only related to the use of corticosteroids, but also to demographic factors, the activity of the disease, and the systemic inflammation associated with autoimmunity.

An Overview of Trichobacteriosis (Trichomycosis): An Underdiagnosed Disease.

Trichobacteriosis (trichomycosis) is an asymptomatic infection at the axillary hair level caused by a bacterium of Corynebacterium spp. The aim of this study is to identify the clinical, epidemiological, and microbiological characteristics of previously reported cases. A review was conducted including the cases of trichomycosis (trichobacteriosis) reported in the PubMed database up to June 2023. Twenty-nine articles were included, involving 365 patients in total. A higher incidence was observed in men, representing 94% of the cases, most of which were in the age range of 20-50 years. The most frequently affected clinical topography was the axillar (90% of the cases). Most of the patients presented change in hair texture and bromhidrosis, some other frequent clinical manifestations were hyperhidrosis, hair color change, and cromhidrosis; 6% of the patients were asymptomatic. The etiological agent most frequently identified was Corynebacterium spp., the flavescens variety being the most prevalent. The most common form of treatment was shaving and topical clindamycin. In conclusion, trichobacteriosis is an infection that most frequently affects men at the axillary level; it manifests clinically with few symptoms and usually has a good response to treatment.

Necrotizing pneumonia due to Saprochaete capitata in a patient with diabetes mellitus. Case report.

Saprochaete capitata is a yeast-like fungus of the Dipodascaceae family, capable of colonizing the skin and the respiratory and gastrointestinal tracts. We present a 56-year-old man with diabetes mellitus who was admitted to the hospital presenting with fever, cough and hemoptysis. The diagnosis of necrotizing pneumonia was made by direct microscopy of the bronchoalveolar lavage fluid showed and Saprochaete capitata was identified by Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF MS®). Treatment consisted of itraconazole 200 mg every 12 hours orally for 30 days, leading to clinical and radiological improvement. Saprochaete capitata infection is a rare cause of pulmonary mycoses.

First case report of tinea corporis caused by Trichophyton indotineae in Latin America.

A case of tinea corporis by Trichophyton indotineae observed in Argentina is presented. The patient had a history of having spent 18 months in Tulum, Mexico. She was suffering from tinea corporis in the anterior region of both thighs and the gluteal area. A mycological study was performed and T. mentagrophytes complex was isolated. The fungus was later identified as T. indotineae by DNA sequencing and treatment with SUBA-itraconazole was initiated with good clinical response.

Mixed oral candidiasis in type 2 diabetic patients: Identification and spectrum of sensitivity / Candidiasis oral mixta en pacientes con diabetes de tipo 2: identificación y espectro de sensibilidad

Introduction: Patients with type 2 diabetes mellitus are susceptible to acquire Candida spp. infections, sometimes involving more than one species. The resistance of some species to antimycotic agents can cause treatment failure. Objectives: To determine the frequency and clinical varieties of mixed oral candidiasis in patients with type 2 diabetes mellitus, the involved species, and its sensitivity spectra when exposed to antifungals used as candidiasis treatment. Material and methods: We developed an analytical cross-sectional study with 72 patients with type 2 diabetes mellitus with hyperglycemia (HbA1C ≥ 7%) and an oral candidiasis diagnosis. The causal species of oral candidiasis were identified through microbiological techniques, and sensitivity tests were carried out using the diffusion method in a plate with strips (E-test ®). Results: We included 72 patients in the study, 32 (44%) males and 40 (56%) females. Patients were divided into three age groups: young adults (17%), adults (74%), and older adults (9%). The mean age of the patients was 51 years. No significant differences were found between mixed oral candidiasis and groups (sex and age), or between mixed oral candidiasis and gender, glycosylated hemoglobin level (HbA1C), antihyperglycemic treatment, or type 2 diabetes mellitus time of diagnosis. We found a correlation between the adult group and development of mixed or simple oral candidiasis. The results showed eight (13%) cases of mixed oral candidiasis: seven with a coinfection of two species and one with a coinfection of three species. The identified species were Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis, and C. krusei. Most of these species presented sensitivity against ketoconazole and fluconazole, and higher resistance to itraconazole. Conclusions: Mixed oral candidiasis occurs in approximately 10% of the patients with type 2 diabetes mellitus and its treatment can be ineffective when the etiological agent is not identified.

Introducción: Los pacientes con diabetes mellitus de tipo 2 son propensos a adquirir infecciones por Candida spp., en ocasiones, causadas por más de una especie. La resistencia de algunas de ellas puede resultar en complicaciones médicas por falla del tratamiento. Objetivos: Determinar la frecuencia y las variedades clínicas de la candidiasis oral mixta en pacientes con diabetes mellitus de tipo 2, las especies de Candida involucradas y sus espectros de sensibilidad a los antifúngicos utilizados como tratamiento. Material y métodos. Se hizo un estudio transversal analítico en pacientes con diabetes mellitus de tipo 2, hiperglucemia (superior o igual al 7 % de la hemoglobina glucosilada, HbA1C) y con diagnóstico clínico de candidiasis oral. Mediante técnicas microbiológicas, se identificaron las especies causales de la candidiasis oral. Las pruebas de sensibilidad se llevaron a cabo con el método de difusión en placa con tiras (E-test®). Resultados: Se incluyeron 72 pacientes: 32 (44 %) hombres y 40 (56 %) mujeres, clasificados en tres grupos de edad: jóvenes adultos (17 %), adultos (74 %) y ancianos (9 %), con una media de 51 años. No se encontraron diferencias significativas en la candidiasis oral según los grupos de sexo y edad, ni entre las candidiasis orales mixtas y el sexo, el porcentaje de HbA1C, el tratamiento antihiperglucemiante o el tiempo de diagnóstico de la diabetes mellitus de tipo 2. En el grupo etario de adultos, se encontró una correlación con las candidiasis mixtas o simples. Se encontraron 8 (13 %) casos de candidiasis mixtas: siete con coinfección por dos especies de Candida y uno con coinfección por tres especies. Las especies identificadas en ellos, fueron: Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis y C. krusei. La mayoría de estas especies presentó sensibilidad a ketoconazol y fluconazol, y mayor resistencia a itraconazol. Conclusiones: Las candidiasis orales mixtas se presentan, aproximadamente, en el 10 % de los pacientes con diabetes mellitus de tipo 2 y el tratamiento puede ser ineficaz cuando no se identifica el agente etiológico.

Candidiasis oral mixta en pacientes con diabetes de tipo 2: identificación y espectro de sensibilidad / Mixed oral candidiasis in type 2 diabetic patients: Identification and spectrum of sensitivity

Introducción. Los pacientes con diabetes mellitus de tipo 2 son propensos a adquirir infecciones por Candida spp., en ocasiones, causadas por más de una especie. La resistencia de algunas de ellas puede resultar en complicaciones médicas por falla del tratamiento. Objetivos. Determinar la frecuencia y las variedades clínicas de la candidiasis oral mixta en pacientes con diabetes mellitus de tipo 2, las especies de Candida involucradas y sus espectros de sensibilidad a los antifúngicos utilizados como tratamiento. Materiales y métodos. Se hizo un estudio transversal analítico en pacientes con diabetes mellitus de tipo 2, hiperglucemia (superior o igual al 7 % de la hemoglobina glucosilada, HbA1C) y con diagnóstico clínico de candidiasis oral. Mediante técnicas microbiológicas, se identificaron las especies causales de la candidiasis oral. Las pruebas de sensibilidad se llevaron a cabo con el método de difusión en placa con tiras (E-test®). Resultados. Se incluyeron 72 pacientes: 32 (44 %) hombres y 40 (56 %) mujeres, clasificados en tres grupos de edad: jóvenes adultos (17 %), adultos (74 %) y ancianos (9 %), con una media de 51 años. No se encontraron diferencias significativas en la candidiasis oral según los grupos de sexo y edad, ni entre las candidiasis orales mixtas y el sexo, el porcentaje de HbA1C, el tratamiento antihiperglucemiante o el tiempo de diagnóstico de la diabetes mellitus de tipo 2. En el grupo etario de adultos, se encontró una correlación con las candidiasis mixtas o simples. Se encontraron 8 (13 %) casos de candidiasis mixtas: siete con coinfección por dos especies de Candida y uno con coinfección por tres especies. Las especies identificadas en ellos, fueron: Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis y C. krusei. La mayoría de estas especies presentó sensibilidad a ketoconazol y fluconazol, y mayor resistencia a itraconazol. Conclusiones. Las candidiasis orales mixtas se presentan, aproximadamente, en el 10 % de los pacientes con diabetes mellitus de tipo 2 y el tratamiento puede ser ineficaz cuando no se identifica el agente etiológico.

Introduction. Patients with type 2 diabetes mellitus are susceptible to acquire Candida spp. infections, sometimes involving more than one species. The resistance of some species to antimycotic agents can cause treatment failure. Objectives. To determine the frequency and clinical varieties of mixed oral candidiasis in patients with type 2 diabetes mellitus, the involved species, and its sensitivity spectra when exposed to antifungals used as candidiasis treatment. Materials and methods. We developed an analytical cross-sectional study with 72 patients with type 2 diabetes mellitus with hyperglycemia (HbAIC s 7%) and an oral candidiasis diagnosis. The causal species of oral candidiasis were identified through microbiological techniques, and sensitivity tests were carried out using the diffusion method in a plate with strips (E-test ®). Results. We included 72 patients in the study, 32 (44%) males and 40 (56%) females. Patients were divided into three age groups: young adults (17%), adults (74%), and older adults (9%). The mean age of the patients was 51 years. No significant differences were found between mixed oral candidiasis and groups (sex and age), or between mixed oral candidiasis and gender, glycosylated hemoglobin level (HbA1C), antihyperglycemic treatment, or type 2 diabetes mellitus time of diagnosis. We found a correlation between the adult group and development of mixed or simple oral candidiasis. The results showed eight (13%) cases of mixed oral candidiasis: seven with a coinfection of two species and one with a coinfection of three species. The identified species were Candida albicans, C. glabrata, C. dubliniensis, C. kefyr, C. tropicalis, and C. krusei. Most of these species presented sensitivity against ketoconazole and fluconazole, and higher resistance to itraconazole. Conclusions. Mixed oral candidiasis occurs in approximately 10% of the patients with type 2 diabetes mellitus and its treatment can be ineffective when the etiological agent is not identified.

An update on the development of novel antifungal agents for eumycetoma.

Eumycetoma, a chronic subcutaneous mycosis, responds poorly to the available antifungal treatments and patients often require extensive surgical resection or amputation of the affected limb. More effective treatments are needed for eumycetoma. This article will describe some of the approaches being used to develop and evaluate new treatments for eumycetoma, summarise the latest developments and discuss the challenges that lie ahead.

High-Throughput Microsatellite Markers Development for Genetic Characterization of Emerging Sporothrix Species.

Sporotrichosis is the main subcutaneous mycosis worldwide transmitted by animal or plant vectors and often escalates to outbreaks or epidemics. The current cat-transmitted sporotrichosis driven by Sporothrix brasiliensis has become a significant public health issue in South America. Transmission dynamics remain enigmatic due to the lack of development of polymorphic markers for molecular epidemiological analysis. This study used a high-throughput mining strategy to characterize simple sequence repeat (SSR) markers from Sporothrix genomes. A total of 118,140-143,912 SSR loci were identified (82,841-98,369 unique markers), with a 3651.55-3804.65 SSR/Mb density and a majority of dinucleotides motifs (GC/CG). We developed a panel of 15 highly polymorphic SSR markers suitable for genotyping S. brasiliensis, S. schenckii, and S. globosa. PCR amplification revealed 240 alleles in 180 Sporothrix isolates with excellent polymorphic information content (PIC = 0.9101), expected heterozygosity (H = 0.9159), and discriminating power (D = 0.7127), supporting the effectiveness of SSR markers in uncovering cryptic genetic diversity. A systematic population genetic study estimated three clusters, corresponding to S. brasiliensis (population 1, n = 97), S. schenckii (population 2, n = 49), and S. globosa (population 3, n = 34), with a weak signature of mixed ancestry between populations 1 and 2 or 3 and 2. Partitioning of genetic variation via AMOVA revealed highly structured populations (ΦPT = 0.539; Nm = 0.213; p < 0.0001), with approximately equivalent genetic variability within (46%) and between (54%) populations. Analysis of SSR diversity supports Rio de Janeiro (RJ) as the center of origin for contemporary S. brasiliensis infections. The recent emergence of cat-transmitted sporotrichosis in northeastern Brazil indicates an RJ-Northeast migration resulting in founder effects during the introduction of diseased animals into sporotrichosis-free areas. Our results demonstrated high cross-species transferability, reproducibility, and informativeness of SSR genetic markers, helping dissect deep and fine-scale genetic structures and guiding decision making to mitigate the harmful effects of the expansion of cat-transmitted sporotrichosis.

Diagnosis and Treatment of Pulmonary Coccidioidomycosis and Paracoccidioidomycosis.

Coccidioidomycosis (CM) and paracoccidioidomycosis (PCM) are systemic mycoses that are highly endemic in Latin America and have recently been included on the World Health Organization (WHO) Fungal Priority Pathogens List. Coccidioides immitis and Coccidioides posadasii are recognized as etiological agents of CM, with peculiarities in their geographic distribution. The genus Paracoccidioides now includes Paracoccidioides lutzii and the Paracoccidioides brasiliensis complex, which encompasses four phylogenetic species. In both diseases, pulmonary signs and symptoms are the main reasons for patients to seek medical assistance, and they are frequently misdiagnosed as tuberculosis. In this paper, we present a critical view of the strategies for diagnosis and clinical management of CM and PCM. Over the past few decades, there has been an increase in the number of reports of endemic fungal infections in areas previously thought to be "non-endemic" due to climate change and increased travel, among other factors. Learning to recognize their main epidemiological aspects and clinical manifestations is crucial so that clinicians can include them in the differential diagnosis of lung disease and avoid late diagnosis.

Physiological characterization and molecular identification of Saccharomycopsis fibuligera as the etiological agent of a skin lesion.

Routine laboratory methods are not effective in identifying cryptic species resulting in the underreporting of infections caused by non-Candida yeasts. This paper presents the physiological characteristics and antifungal susceptibility of Saccharomycopsis fibuligera 12-771, isolated from a tinea-like lesion. Isolate 12-771 was identified by ITS and D1/D2 analysis as S. fibuligera. The isolate presented an auxonogram profile similar to Candida utilis, as well as protease, esterase and hemolysin activity. MICs were of 0.25 â€‹µg/mL for amphotericin B, 1-2 â€‹µg/mL for echinocandins, and 16 â€‹µg/mL for fluconazole. This work represents the first record in America of S. fibuligera as an infectious agent.

Diagnostics to support mycetoma management-Development of two target product profiles.

OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different microorganisms and identified by the WHO as one of the high-priority diseases for developing diagnostic tests. To ensure the production of diagnostic assays for use by clinical staff in endemic regions, target product profiles (TPPs) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another that would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a 1-month online public consultation on 25 October 2021, and the final TPP was posted online on 5 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them.

Ocular Fungal Infections.

Fungal infections of the eye continue to be an important cause of ocular morbidity and loss of vision, particularly in the developing world [...].

Encapsulated eumycetoma caused by Biatriospora mackinnonii.

Eumycetoma is a chronic infection due to filamentous fungi. Herein, we report a case of eumycetoma presenting as a subcutaneous encapsulated lesion on the right leg with no previous traumatic implantation. From microscopic morphological characteristics and molecular analysis, the pathogenic fungal species were identified as Biatriospora mackinnonii. Surgical excision of the entire lesion was performed to reduce the fungal load and improve antifungal therapy response.

Current situation of endemic mycosis in the Americas and the Caribbean: Proceedings of the first international meeting on endemic mycoses of the Americas (IMEMA).

BACKGROUND: The Americas are home to biologically and clinically diverse endemic fungi, including Blastomyces, Coccidioides, Emergomyces, Histoplasma, Paracoccidioides and Sporothrix. In endemic areas with high risk of infection, these fungal pathogens represent an important public health problem. OBJECTIVES: This report aims to summarise the main findings of the regional analysis carried out on the status of the endemic mycoses of the Americas, done at the first International Meeting on Endemic Mycoses of the Americas (IMEMA). METHODS: A regional analysis for the Americas was done, the 27 territories were grouped into nine regions. A SWOT analysis was done. RESULTS: All territories reported availability of microscopy. Seventy percent of territories reported antibody testing, 67% of territories reported availability of Histoplasma antigen testing. None of the territories reported the use of (1-3)-ß-d-glucan. Fifty two percent of territories reported the availability of PCR testing in reference centres (mostly for histoplasmosis). Most of the territories reported access to medications such as trimethoprim-sulfamethoxazole, itraconazole, voriconazole and amphotericin B (AMB) deoxycholate. Many countries had limited access to liposomal formulation of AMB and newer azoles, such as posaconazole and isavuconazole. Surveillance of these fungal diseases was minimal. CONCLUSIONS: A consensus emerged among meeting participants, this group concluded that endemic mycoses are neglected diseases, and due to their severity and lack of resources, the improvement of diagnosis, treatment and surveillance is needed.

Evaluation of the synergistic antifungal activity of micafungin and voriconazole plus sertraline against Candida auris.

Candida auris is an emerging global public health threat. It is an opportunistic yeast that usually affects critically ill patients in healthcare settings and is characterized by reduced susceptibility to multiple antifungal classes. Combination therapy with antifungals and repurposed drugs is a feasible alternative to overcome this problem. The aim of this study was to examine the in vitro interactions and potential synergy of micafungin (MFG) and voriconazole (VRC) plus the antidepressant sertraline (SRT) against clinical isolates of C. auris. Conventional antifungal testing was first performed with the three drugs according to the CLSI methodology. Drug interactions were determined by the checkerboard microdilution assay using the fractional inhibitory concentration (FIC) index. Synergistic interactions were noted with the combination of MFG and SRT plus VRC with FIC values of 0.37 to 0.49 for some strains. Indifferent interactions were observed when MFG was combined with SRT with just one exception (FIC 0.53). No antagonism was observed for any combination. The combination of VRC with MCF or SRT may be relevant for treating C. auris infections.