Invasive aspergillosis: A comprehensive review.

Invasive aspergillosis (IA) is a severe fungal infection caused by Aspergillus species, particularly Aspergillus fumigatus, although new species, sometimes resistant to antifungals are becoming more common. IA predominantly affects immunocompromised patients, such as those with haematological malignancies, solid organ transplant recipients, and critically ill patients. However, new at-risk populations have emerged in recent years, such as IA associated with severe viral infections. Advanced diagnostic methods are crucial, especially considering the rising concern of antifungal resistance. Early detection is critical for successful treatment, typically involving antifungal medications like voriconazole or amphotericin B, but new antifungals are arriving to complete the therapeutic strategies. Despite advancements, mortality rates remain high, underscoring the importance of timely interventions and ongoing research. Healthcare providers should maintain a high index of suspicion, especially in immunocompromised patients and other new risk factors that are arising, to promptly diagnose and manage invasive aspergillosis.

A Palearctic view of a bat fungal disease.

The fungal infection causing white-nose disease in hibernating bats in North America has resulted in dramatic population declines of affected species, since the introduction of the causative agent Pseudogymnoascus destructans. The fungus is native to the Palearctic, where it also infects several bat species, yet rarely causes severe pathology or the death of the host. Pseudogymnoascus destructans infects bats during hibernation by invading and digesting the skin tissue, resulting in the disruption of torpor patterns and consequent emaciation. Relations among pathogen, host, and environment are complex, and individuals, populations, and species respond to the fungal pathogen in different ways. For example, the Nearctic Myotis lucifugus responds to infection by mounting a robust immune response, leading to immunopathology often contributing to mortality. In contrast, the Palearctic M. myotis shows no significant immunological response to infection. This lack of a strong response, resulting from the long coevolution between the hosts and the pathogen in the pathogen's native range, likely contributes to survival in tolerant species. After more than 15 years since the initial introduction of the fungus to North America, some of the affected populations are showing signs of recovery, suggesting that the fungus, hosts, or both are undergoing processes that may eventually lead to coexistence. The suggested or implemented management methods of the disease in North America have encompassed, for example, the use of probiotics and fungicides, vaccinations, and modifying the environmental conditions of the hibernation sites to limit the growth of the pathogen, intensity of infection, or the hosts' responses to it. Based on current knowledge from Eurasia, policy makers and conservation managers should refrain from disrupting the ongoing evolutionary processes and adopt a holistic approach to managing the epizootic.

Vista paleártica de una enfermedad fúngica de murciélagos Resumen La enfermedad fúngica que produce el síndrome de nariz blanca en murciélagos en hibernación en Norte América ha resultado en declinaciones poblacionales dramáticas en las especies afectadas desde la introducción del agente causante, Pseudogymnoascus destructans. El hongo es nativo del Paleártico, donde también infecta a varias especies de murciélagos; sin embargo, raramente causa patología severa o la muerte del hospedero. Pseudogymnoascus destructans infecta a los murciélagos durante la hibernación invadiendo y digiriendo el tejido de la piel, lo que resulta en la disrupción de los patrones de torpor y la consecuente emaciación. Las relaciones entre el patógeno, el huésped y el ambiente son complejas, y los individuos, las especies y poblaciones responden al patógeno fúngico de distintas maneras. Por ejemplo, Myotis lucifugus, especie del Neártico, responde a la infección montando una respuesta inmune robusta, produciendo una inmunopatología que a menudo contribuye a la mortalidad. En contraste, M. myotis del Paleártico no presenta respuesta inmunológica significativa a la infección. La falta de una fuerte respuesta, resultado de la larga coevolución entre hospederos y el patógeno en el rango nativo de distribución del patógeno, probablemente contribuye a la supervivencia en especies tolerantes. Después de más de 15 años desde la introducción del hongo en Norte América, algunas de las poblaciones afectadas están mostrando señales recuperación, lo que sugiere que el hongo, hospederos, o ambos, están pasando por procesos que eventualmente pueden conducir a la coexistencia. Los métodos de manejo de la enfermedad sugeridos o implementados en Norte América han abarcado, por ejemplo, el uso de probióticos y fungicidas, vacunaciones y modificación de las condiciones ambientales de los sitios de hibernación para limitar el crecimiento del patógeno, la intensidad de la infección o las respuestas de los hospederos. Con base en conocimiento actual de Eurasia, los formuladores de políticas y los manejadores de la conservación deberían abstenerse de alterar los procesos evolutivos en curso y adoptar un enfoque holístico para gestionar la epizootia.

Etiología, clínica y evolución de infecciones fúngicas invasoras en pacientes con neoplasias hematológicas en un hospital universitario de Argentina / Etiology, clinical characteristics and outcomes of invasive fungal infection in patients with hematological malignancies in a university hospital in Argentina

INTRODUCCIÓN: Las infecciones fúngicas invasoras (IFI) en pacientes con neoplasias hematológicas (NH) representan un desafío diagnóstico y terapéutico. OBJETIVOS: Describir la etiología, características clínicas, diagnóstico y evolución de los episodios de IFI probadas y probables en pacientes con NH y trasplante de progenitores hematopoyéticos (TPH). PACIENTES Y MÉTODOS: Estudio descriptivo, retrospectivo y de cohorte que incluyó IFI probadas y probables en pacientes adultos con NH y TPH. Se realizó seguimiento hasta el día 90. RESULTADOS: Se incluyeron 80 episodios de IFI: 49% probadas y 51% probables, 67,5% por hongos filamentosos (HF), 30% por hongos levaduriformes (HL) y 2,5% por hongos dimorfos. Los tipos de IFI más frecuentes fueron aspergilosis invasoras pulmonares (AP) y candidiasis invasoras (CI), en su mayoría por Candida spp. no albicans. Todos los casos de AP se diagnosticaron por detección de galactomanano en sangre y/o lavado broncoalveolar, y solamente 22,2% presentaban nódulos con halo en la tomografía computada (TC) de tórax, siendo los infiltrados inespecíficos los hallazgos más frecuentes. Tuvieron coinfección bacteriana y viral el 30 y 17,5%, respectivamente. El 50% fueron IFI de brecha, y la mortalidad global y mortalidad relacionada a la IFI fue 51 y 24%, respectivamente. CONCLUSIÓN: Los HF fueron la principal causa de IFI, con una gran proporción de IFI de brecha, y presentaron elevada mortalidad. Para el diagnóstico, resulta importante la utilización de biomarcadores y jerarquizar cualquier imagen patológica en la TC.

BACKGROUND: Invasive fungal infections (IFI) in patients with hematological malignancies (HM) represent a diagnostic and therapeutic challenge. AIM: To describe the etiology, clinical characteristics, diagnosis and evolution of proven and probable IFI episodes in patients with HM and hematopoietic stem cell transplantation (HSCT). METHODS: Retrospective, descriptive, cohort study performed in adult patients with HM and HSCT, who developed proven and probable IFI. Follow-up was carried out until day 90. RESULTS: A total of 80 IFI episodes were included: 49% proven and 51% probable, 67,5% due to mold (M), 30% to yeast-like fungi (Y) and 2,5% to dimorphic fungi. The most frequent causes were probable pulmonary aspergillosis (PA) and invasive candidiasis (IC), mainly due to non-albicans Candida species. PA were all diagnosed by detection of galactomannan (GM) in blood and bronchoalveolar lavage, and only 22,2% presented halo sign on chest CT. Bacterial and viral coinfections were reported in 30% and 17,5% respectively. Breakthrough IFI occurred in 50%, and global and IFI-related mortality were 51% and 24% respectively. CONCLUSION: Mold was the main cause of IFI, with a large proportion of breakthrough IFI, presenting high mortality. The use of biomarkers and the classification of any pathological image on CT contribute to the diagnosis.

Mucormicosis maxilar asociado a COVID-19, tratamiento médico-quirúrgico y manejo multidisciplinario. Reporte de caso / Maxillary mucormycosis associated with COVID-19, medical-surgical treatment and multidisciplinary management. Case report

Resumen Introducción: Durante la actual pandemia de COVID-19 múltiples complicaciones se han desarrollado posterior a la enfermedad, dentro de las cuales se encuentran las infecciones fúngicas, como la mucormicosis, que puede resultar directamente de la infección por COVID-19 y/o como efecto secundario de los fármacos utilizados en su tratamiento. La mucormicosis es una infección causada por un grupo de hongos llamados mucormycetes; a nivel rinocerebral se presenta con celulitis facial, cefalea, proptosis, movilización del diente afectado y secreción nasal. Reporte de caso: Se presenta a un paciente femenino de 57 años con antecedente de neumonía grave por COVID-19 con posterior desarrollo de absceso periodontal que ameritó extracción del segundo molar superior derecho con posterior formación de fistula. Se toma TC de macizo facial donde se evidencia erosión ósea con pérdida de la morfología habitual y en pared anterior del seno maxilar derecho. Se realiza biopsia reportando tejido óseo con elementos micóticos (hifas aseptadas) morfológicamente compatibles con mucor sp. Se realizó tratamiento con anfotericina B y hemimaxilectomia derecha. Actualmente se encuentra en tratamiento con pozaconazol, y lavados quirúrgicos. Conclusión: La enfermedad de COVID-19 es una enfermedad muy común actualmente a nivel mundial, por lo que es importante identificar y llevar un seguimiento de aquellas personas con factores de riesgo para desarrollar mucormicosis; el diagnóstico y un plan de tratamiento temprano es fundamental para evitar complicaciones, las cuales pueden originar un desenlace fatal.

Abstract Introduction: During the current pandemic of COVID-19 multiple complications have developed after the disease, among which are fungal infections, such as mucormycosis, which can result directly from COVID-19 infection and/or as a side effect of the drugs used in its treatment. Mucormycosis is an infection caused by a group of fungi called mucormycetes; at the rhinocerebral level it presents with facial cellulitis, headache, proptosis, mobilization of the affected tooth and nasal secretion. Case report: the following is a 57-year-old female patient with a history of severe pneumonia due to COVID-19 with subsequent development of periodontal abscess that merited extraction of the upper right second molar with subsequent fistula formation. The patient started an infection with the presence of purulent secretion in the extraction area of the right molar. A CT scan of the facial mass was taken showing bone erosion with loss of the usual morphology in the right upper maxillary bone and anterior wall of the right maxillary sinus, as well as a biopsy of the right maxilla reporting bone tissue with mycotic elements (aseptates hyphae) morphologically compatible with mucor sp. Treatment with amphotericin B and right hemimaxillectomy was performed. She is currently being treated with pozaconazole and surgical washings. Conclusion: COVID-19 disease is currently a very common disease worldwide, so it is important to identify and follow up those people with risk factors for developing mucormycosis; early diagnosis and treatment plan is essential to avoid complications, which can lead to a fatal outcome.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020 / Invasive fungal infections in children with cancer and severe aplastic anemia in nine hospitals from PINDA Network, Chile. 2016-2020

INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP).

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

Documento de consenso de manejo de neutropenia febril en el paciente pediátrico oncohematológico de la Sociedad Española de Infectología Pediátrica (SEIP) y la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP) / Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP)

La neutropenia febril es una de las principales complicaciones infecciosas que sufren los pacientes pediátricos oncohematológicos, y a pesar los avances en diagnóstico y tratamiento, siguen condicionando una mortalidad y morbilidad significativa. Estos pacientes agrupan una serie de factores de riesgo de infección, donde destaca la neutropenia asociada a quimioterapia, la disrupción de barreras cutáneo-mucosas y el uso de dispositivos intravasculares. El abordaje diagnóstico y terapéutico precoz de los episodios de neutropenia febril en los pacientes oncohematológicos, ajustado a las características individuales de cada paciente, es fundamental para mejorar su pronóstico. Por ello, diseñar protocolos de abordaje, que sistematicen su atención, permite optimizar y homogeneizar su abordaje. Además, racionalizar el uso de los antimicrobianos, ajustando la duración y el espectro de los mismos, es crucial para hacer frente al incremento de resistencias a antimicrobianos. El objetivo de este documento, elaborado entre la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Hematología y Oncología Pediátrica, es dar recomendaciones de consenso sobre el manejo de la neutropenia febril en el paciente oncohematológico, respecto al abordaje inicial, terapia secuencial y de soporte e infección fúngica invasiva, que cada centro debe adaptar a las características de sus pacientes y epidemiología local. (AU)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends. (AU)

Unmasking the uncommon: post COVID-19's sinister encore. A clinical report of acute invasive fungal rhinosinusitis in a non-diabetic, non-steroid therapy patient / Descubriendo lo inusual: el siniestro epílogo post-COVID-19. Informe clínico de una rinosinusitis fúngica invasiva aguda en un paciente no diabético, sin terapia de esteroides

COVID-19, caused by SARS-CoV-2, has been linked to various bacterial and fungal infections. The incidence of mucormycosis has notably increased in individuals with COVID-19, with many cases reported globally, especially in India. The risk factors for developing mucormycosis include uncontrolled diabetes and use of immunosuppressants such as corticosteroids. We report a case of acute invasive fungal rhino-sinusitis (mucormycosis) in a 42 year old patient with no history of diabetes or steroid therapy but recently diagnosed with COVID-19. The patient presented with facial swelling, loose teeth, and imaging findings consistent with mucormycosis. The history, examination, and laboratory investigations were sufficient to exclude other causes of immunocompromised status in the patient. The diagnosis was confirmed through KOH staining of excised tissue, which tested positive for mucor. The patient underwent systemic antifungal therapy and Functional Endoscopic Sinus surgery (FESS) associated with a bilateral maxillectomy to remove the affected tissue. These interventions were successful, and the patient experienced a positive clinical response. This case report details an uncommon presentation of post COVID-19 acute invasive fungal rhino-sinusitis in a patient without typical risk factors for the infection. Therefore, clinicians should have a high index of suspicion for mucormycosis in patients with a recent history of COVID-19 infection, especially those with symptoms such as facial swelling or tooth loss. Prompt detection and management of mucormycosis are critical for improving patient outcomes. However, delays in diagnosis and treatment can lead to significant morbidity and mortality. (AU)

La COVID-19, causada por el virus SARS-CoV-2, se ha relacionado con varias infecciones bacterianas y fúngicas. La incidencia de mucormicosis ha aumentado notablemente en individuos con COVID-19, habiéndose reportado muchos casos a nivel mundial, especialmente en la India. Los factores de riesgo para desarrollar mucormicosis incluyen diabetes descontrolada y el uso de inmunosupresores como los corticosteroides. Presentamos un caso de rinosinusitis fúngica invasiva aguda (mucormicosis) en un paciente de 42 años sin antecedentes de diabetes ni terapia con esteroides, pero recientemente diagnosticado con COVID-19. El paciente presentaba hinchazón facial, movilidad dental y hallazgos de imágenes consistentes con mucormicosis. La historia clínica, el examen físico y las investigaciones de laboratorio fueron suficientes para descartar otras causas de inmunocompromiso en el paciente. El diagnóstico se confirmó mediante tinción con KOH del tejido extirpado, que resultó positiva para mucor. El paciente recibió terapia antifúngica sistémica y se sometió a una cirugía endoscópica funcional de senos paranasales (FESS) junto con una maxilectomía bilateral para extirpar el tejido afectado. Estas intervenciones fueron exitosas y el paciente experimentó una respuesta clínica positiva.Este informe de caso detalla una presentación poco común de rinosinusitis fúngica invasiva aguda post-COVID-19 en un paciente sin factores de riesgo típicos para la infección. Por lo tanto, los médicos deben tener un alto índice de sospecha de mucormicosis en pacientes con antecedentes recientes de infección por COVID-19, especialmente aquellos con síntomas como hinchazón facial o pérdida de dientes. La detección y el manejo oportunos de la mucormicosis son fundamentales para mejorar los resultados del paciente. Sin embargo, los retrasos en el diagnóstico y el tratamiento pueden provocar una morbilidad y mortalidad significativas. (AU)

Entomoftoromicosis por Conidiobolus coronatus en un paciente joven proveniente de área rural / Entomophthoromycosis due to Conidiobolus coronatus in a young patient from a rural area

La conidiobolomicosis es una micosis subcutánea causada por un hongo saprofito, Conidiobulus spp. perteneciente a la clase Zigomicetos, orden Entomoftorales, que habita en regiones tropicales. La manifestación clínica clásica es la deformidad progresiva de estructuras faciales y su diagnóstico se basa en cultivos de la zona afectada y el estudio histopatológico, siendo el "fenómeno de Splendore-Hoeppli" el hallazgo más característico. Dada su baja frecuencia de presentación, no existe consenso sobre la mejor opción y tiempo de tratamiento. Aquí presentamos un caso de entomoftoromicosis rinofacial causada por Conidiobolus coronatus en un paciente inmunocompetente de la región sur de Colombia.

Conidiobolomycosis is a subcutaneous mycosis caused by a saprophytic fungus, Conidiobulus, belonging to the class of Zygomycetes, an order of Entomophtorales that inhabits tropical regions. Its most frequent clinical manifestation is the progressive deformity of facial midline structures, and the diagnosis is based on cultures taken from the affected area and the histopathological study, being the "Splendore-Hoeppli phenomenon" the most characteristic finding. Due to its low frequency of presentation, there is no consensus about the best option and treatment time. We present a case of rhinofacial entomophthoromycosis caused by Conidiobolus coronatus in an immunocompetent patient from the southern region of Colombia.

Una experiencia de siete años en el laboratorio de Micología del Hospital de Pediatría Juan P. Garrahan / A seven-year experience in the Mycology Laboratory of Hospital de Pediatría Juan P. Garrahan

En noviembre del año 2015 nos incorporamos al Laboratorio de Micología del Servicio de Microbiología del Hospital Garrahan. En este breve resumen queremos compartir los avances logrados a través de nuestra experiencia durante siete años de trabajo profesional. Debido a los diagnósticos realizados y su complejidad, consideramos que el Hospital Garrahan, sus pacientes y la comunidad toda necesitan contar con un laboratorio de Micología que responda a sus necesidades. Creemos haber iniciado un camino que esperamos continúe y culmine con la creación de la Unidad de Micología (AU)

In November 2015 we joined the Mycology Laboratory of the Microbiology Service of the Hospital Garrahan. In this brief summary we want to share the advances achieved through our experience during seven years of professional work. Due to the diagnosis made and their complexity, we believe that the Hospital Garrahan, its patients and the entire community, need to have a Mycology laboratory that responds to their requirements. We believe we have started a path that we hope will continue and culminate with the creation of the Mycology Unit (AU)

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient / COVID-19 asociado a histoplasmosis diseminada en un paciente trasplantado renal

Abstract We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Resumen Se presenta un caso de histoplasmosis diseminada e infección por COVID-19 en un paciente trasplantado renal en Argentina. El paciente presentó un cuadro clínico respiratorio, y la tomografía computarizada (TC) de tórax mostró múltiples opacidades centrolobulillares bilaterales con patrón de árbol en brote. El paciente fue tratado inicialmente con antibióticos para agentes causantes de neumonía bacteriana adquirida en la comunidad y luego como tuberculosis. Un mes después se le diagnosticó una histoplasmosis diseminada y el hongo fue aislado del esputo, la piel y la mucosa oral. El hongo fue tipificado molecularmente como Histoplasma capsulatum clado LAmB. El paciente fue hospitalizado y se inició tratamiento con anfoteric-ina B liposomal vía intravenosa. Durante el transcurso de la terapia antifúngica los síntomas respiratorios del paciente empeoraron, una nueva TC de tórax mostró una lesión unilateral con apariencia de vidrio esmerilado y se detectó SARS-CoV-2 en el hisopado nasofaríngeo. El paciente fue tratado con plasmoterapia y se modificó el régimen de inmunosupresión (se interrumpió everolimus, se redujo micofenolato de mofetilo y se incrementó la meprednisona). La evolución del paciente fue favorable y fue dado de alta con tratamiento oral con itraconazol.

Aspergillosis by cryptic Aspergillus species: A case series and review of the literature.

BACKGROUND: The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis. AIMS: We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital. METHODS: We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel. RESULTS: A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B. CONCLUSIONS: The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%.

Mucormicosis asociada a COVID-19. Un caso en Argentina / COVID-19 associated mucormycosis. A case in Argentina

Resumen La enfermedad COVID-19 provocada por el virus SARS-CoV-2 presenta una gravedad variable. Recientemente se ha observado un aumento en el número de casos informados de mucormicosis asociada a COVID-19 (CAM), principalmente en personas con diabetes mellitus, cetoacidosis diabética o en tratamiento con esteroides. El mayor número de casos ha sido notificado en India, en donde la prevalencia de CAM en pacientes hospitalizados en el año 2020 fue de 0.27%, lo que implica un aumento en la prevalencia de mucormicosis de 2.1 veces respecto del año 2019. Si bien el tratamiento con corticoides reduce la mortalidad en pacientes con COVID-19 grave, su uso prolongado, en combinación con otros factores clínicos e inmunológicos, puede aumentar el riesgo de infección fúngica invasiva. Comunicamos un caso de CAM en Argentina. El presente informe representa una alerta para fundar sospecha de infección fúngica invasiva en pacientes con COVID-19.

Abstract SARS-CoV-2 virus disease presents variable severity. Recently, an increasing report of cases of COVID-19 associated mucormycosis (CAM) has been observed, mainly in patients with diabetes mellitus, diabetic ketoacidosis or under steroids treatment. The highest number of cases have been reported in India, with a prevalence of 0.27 % in hospitalized patients with COVID-19 during year 2020, which implies a 2.1-fold increase in the prevalence of mucormycosis compared to year 2019. Although corticosteroids treatment reduces mortality in patients with severe COVID-19, its prolonged use, in combination with other clinical and immunological factors, could increase the risk of invasive fungal infection. We report a case of CAM in Argentina. This report represents a warning for considering the diagnosis of invasive fungal infection in patients with severe COVID-19.

Aspergillosis by cryptic Aspergillus species: A case series and review of the literature

Background:The cryptic Aspegillus species are rare, these microorganisms are usually more resistant to common antifungal therapies. Therefore, a correct identification is important when evaluating the impact of such species in aspergillosis.Aims:We aimed to describe the frequency, clinical and microbiological characteristics, and the outcomes of those cases of aspergillosis caused by cryptic species in a tertiary hospital.Methods:We retrospectively identified all microbiologically documented cases of aspergillosis between January 2013 and December 2018. Definitive species identification of clinically significant isolates was achieved via sequencing methods. The polymerase chain reaction (PCR) products were sequenced, and the results obtained were compared to sequences deposited in GenBank. Antifungal susceptibility testing was performed using the Sensititre® YeastOne® panel.Results:A total of 679 Aspergillus isolates were recovered from 489 patients, of which 109 were clinically relevant. Ten (9.2%) isolates were identified as cryptic species: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) and Aspergillus montevidensis (1). Most patients already suffered some type of immunosuppression. Half of these patients had required intensive care before the infection showed up, and most of them had a pulmonary infection. Mortality at the 100-day follow-up was 40%. Antifungal susceptibility testing was performed on three of the isolates (A. arcoverdensis, A. tubingensis and A. nomius), which showed high minimum inhibitory concentrations (MIC) for azoles and amphotericin B.Conclusions:The frequency of cryptic species in our centre was 9.2%. Most patients had some degree of immunosuppression, and the mortality rate was 40%. (AU)

Antecedentes:Las especies crípticas dentro del género Aspergillus son poco habituales, pero suelen mostrar una mayor resistencia al tratamiento antifúngico convencional. Por tanto, una correcta identificación de la especie es necesaria para evaluar el impacto de estas especies crípticas en el desarrollo de la aspergilosis.Objetivos:El objetivo de este estudio fue describir las características clínicas, epidemiológicas y microbiológicas, así como la evolución clínica, de los casos de aspergilosis por especies crípticas en un hospital de tercer nivel.Métodos:Se analizaron de forma retrospectiva todos los casos documentados de aspergilosis con identificación microbiológica entre enero de 2013 y diciembre de 2018. La identificación definitiva de los aislamientos clínicos se realizó mediante métodos de secuenciación. Los productos de amplificación obtenidos por la reacción en cadena de la polimerasa (PCR) fueron secuenciados, y los resultados se analizaron utilizando la base de datos del GenBank. Para el análisis de susceptibilidad a los antifúngicos de los aislamientos identificados se utilizó el panel Sensititre® YeastOne®.Resultados:Se identificaron un total de 679 aislamientos de Aspergillus de 489 pacientes, de los cuales un total de 109 eran clínicamente relevantes. Diez (9,2%) de los aislamientos correspondían a especies crípticas: Aspergillus arcoverdensis (2), Aspergillus lentulus (2), Aspergillus ellipticus (2), Aspergillus alliaceus (1), Aspergillus nomius (1), Aspergillus tubingensis (1) y Aspergillus montevidensis (1). La mayoría de los pacientes tenían algún tipo de inmunosupresión previa. La mitad de estos pacientes habían requerido de cuidados intensivos antes de la infección, y la mayoría sufría una infección pulmonar. La mortalidad a los 100 días de seguimiento fue del 40%. (AU)

Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico / Voriconazole monitorization in pediatric patients, difficulties in dose adjustment

Resumen Presentamos el caso de un escolar de 10 años, con el diagnóstico de una recaída de una leucemia mieloide aguda que cursó con un episodio de una neutropenia febril de alto riesgo, posterior a un ciclo intensivo de quimioterapia, evolucionando con una infección fúngica invasora demostrada por histopatología. Se inició tratamiento con voriconazol intravenoso, evolucionando con concentraciones plasmáticas erráticas que requirieron sucesivos ajustes de dosis, lo que también ocurrió con la administración oral del medicamento. Finalmente, tuvo una respuesta favorable al tratamiento, a pesar de la dificultad de la dosificación para alcanzar niveles terapéuticos. La búsqueda activa y la terapia antifúngica anticipada, así como la monitorización seriada de concentraciones terapéuticas de voriconazol, permitieron un tratamiento antifúngico óptimo y oportuno, mejorando el pronóstico del paciente.

Abstract We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient.

We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Invasive scedosporiosis in lung transplant recipients: A nine-year retrospective study in a tertiary care hospital.

BACKGROUND: Scedosporium species and Lomentospora prolificans (Sc/Lp) are emerging molds that cause invasive disease associated with a high mortality rate. After Aspergillus, these molds are the second filamentous fungi recovered in lung transplant (LT) recipients. AIMS: Our objective was to evaluate the incidence, risk factors and outcome of Sc/Lp infections in LT recipients at a tertiary care hospital with a national reference LT program. METHODS: A nine-year retrospective study was conducted. RESULTS: During this period, 395 LT were performed. Positive cultures for Sc/Lp were obtained from twenty-one LT recipients. Twelve patients (incidence 3.04%) developed invasive scedosporiosis (IS). In 66.7% of the patients with IS the invasive infection was defined as a breakthrough one. The main sites of infection were lungs and paranasal sinuses. Most of the patients received combination antifungal therapy. The IS crude mortality rate after 30 days was 16.7%, and 33.3% after a year. CONCLUSIONS: Our study highlights improved survival rates associated with combination antifungal therapy in LT recipients and underlines the risk of breakthrough infections in patients with allograft dysfunction on nebulized lipidic amphotericin B prophylaxis. In addition to pretransplant colonization, acute or chronic organ dysfunctions seem to be the main risk factors for IS.

[Invasive fungal infection over the last 30 years]. / Evolución de la infección fúngica invasora en los últimos 30 años.

Clinical mycology is in continuous development. The appearance of new clinical guidelines has made it possible to improve the approach to opportunistic fungal infections, especially in immunosuppressed patients (oncohematological and/or transplant recipients). At the same time, the development of new diagnostic tools and new antifungals with a greater spectrum of action and fewer side effects have led to faster diagnoses and treatments that are more effective. Along with these advances, there has been a change in the epidemiology of invasive fungal infection (IFI), with the appearance of new patients (e.g., COPD, liver cirrhosis, post-influenza) and new microorganisms (Candida auris, Lomentospora prolificans, mucorales), and resistant fungi (isolates of Aspergillus resistant to azoles) which the clinician must take into account when choosing the treatment of a patient with an IFI. In this paper we will briefly review the advances in recent decades and the emerging problems.

[Relevance of liposomal amphotericin B in the treatment of invasive fungal infections in patients with hematologic malignancies]. / Relevancia de la anfotericina B liposomal en el tratamiento de las infecciones fúngicas invasoras en pacientes oncohematológicos.

Liposomal amphotericin B (L-AmB) has been a key cornerstone for the management of invasive fungal infections (IFI) caused by a wide array of molds and yeasts during the last three decades. Multiple studies performed over this period have generated a large body of evidence on its efficacy and safety, becoming the main antifungal agent in the management of IFI in patients with hematologic malignancies in several not mutually exclusive clinical settings. First, L-AmB is the most commonly used antifungal agent in patients undergoing intensive chemotherapy for acute leukemia and high-risk myelodysplastic syndrome, as well as in hematopoietic stem cell transplant recipients. Additionally, due to the administration of newer targeted therapies (such as monoclonal antibodies or small molecule inhibitors), opportunistic mold infections are increasingly being reported in patients with hematologic malignancies usually considered low-risk for IFI. These agents usually have a high drug-drug interaction potential, being triazoles, commonly used for antifungal prophylaxis, included. Finally, patients developing breakthrough IFI because of either subtherapeutic concentrations of antifungal prophylactic drugs in blood or selection of resistant strains, require broad spectrum antifungal therapy, usually with an antifungal of a different class. In both situations, L-AmB remains as the best option for early antifungal therapy.