Clinical characteristics, epidemiology, and mortality of patients receiving antifungal therapy at a university hospital of the Triângulo Mineiro, Brazil / Aspectos clínicos, epidemiológicos e mortalidade de pacientes em uso de terapia antifúngica em um hospital universitário do Triângulo Mineiro, Brasil / Aspectos clínicos, epidemiológicos y mortalidad de pacientes en uso de terapia antifúngica en un hospital universitario del Triângulo Mineiro, BrasiL

Background and Objectives: Invasive fungal infections are associated with high morbidity and mortality in patients admitted to hospital, including those receiving appropriate therapy. The aim of this study was to evaluate the use of prophylactic and preemptive antifungal therapy; clinical and epidemiological features; and mortality of patients admitted to an infectious disease ward of a public high complexity hospital in Uberlandia, Minas Gerais, Brazil. Methods: This is a retrospective study carried out in the infectious diseases ward of a public university hospital in Brazil. Data from patients hospitalized in 2019 and 2020 who received azole antifungals (fluconazole, itraconazole, or voriconazole), echinocandin (anidulafungin), and polyene (amphotericin B) were collected from medical records. Results: During the study period, 111 patients received one or more antifungal agent. The length of hospital stays of patients (29.35 days; p=0.0252), mean number of days of antibacterial drug use (23.5 days; p=0.0164), a diagnosis of AIDS (p=0.0397), mechanical ventilation (MV) (p<0.001), and presence of a nasoenteral tube (p<0.01) were variables that were associated with death. Fungal infection was confirmed in 79 (71.2%) patients who used antifungal drugs. The most frequent fungi isolated were Candida spp. (36; 32.4%) and Cryptococcus spp. (22; 19.8%), and there was an association between infection with these fungi and mortality (p<0.05; OR: 7.61 and 5.53, respectively). Regarding antifungal therapy indication, 56 (50.4%) patients received it as empirical therapy, 33 (29.7%) as targeted therapy, and 22 (19.8%) as preemptive therapy. Conclusion: The factors that contributed to mortality of the patients were longer hospital stays, AIDS, antibacterial medication use, mechanical ventilation, and presence of a nasoenteral tube. The type of antifungal therapy used did not influence the mortality in these patients.(AU)

Justificativa e Objetivos: As infecções fúngicas invasivas apresentam alta morbimortalidade para pacientes hospitalizados, inclusive para aqueles em uso de terapia apropriada. O objetivo foi avaliar a terapia antifúngica profilática e preemptiva, as características clínicas e epidemiológicas, e a mortalidade de pacientes internados em uma enfermaria de doenças infecciosas de um hospital público de alta complexidade de Uberlândia, Minas Gerais, Brasil. Métodos: Trata-se de estudo retrospectivo realizado em uma enfermaria de doenças infecciosas. Os dados coletados dos prontuários foram referentes aos pacientes internados nos anos de 2019 e 2020 e que fizeram uso de antifúngicos azólicos (fluconazol, itraconazol ou voriconazol), equinocandinas (anidulafungina) e poliênicos (anfotericina B). Resultados: Durante o período, 111 pacientes usaram um ou mais antifúngicos. O tempo de internação (29,35 dias, p= 0,0252), média de dias de uso de antibacterianos (23,5 dias; p=0,0164), aids (p=0,0397), uso de ventilação mecânica (VM; p <0,001) e uso de sonda nasoenteral (p<0,01) foram variáveis que se relacionaram com desfecho morte. A infecção por fungos foi confirmada em cultura para 79 (71,2%) pacientes em terapia antifúngica. Os fungos mais frequentes foram Candida spp. (36; 32,4%) e Cryptococcus spp. (22; 19,8%), mostrando relação da infecção por esses fungos com a mortalidade (p<0,05; OR: 7,61 e 5,53, respectivamente). Quanto à terapia, 56 (50,4%) pacientes estavam em terapia empírica; 33 (29,7%) usaram como terapia alvo; e 22 (19,8%) usavam como terapia preemptiva. Conclusão: A mortalidade foi mais frequente entre os pacientes com maior tempo de hospitalização, que tinham aids e que fizeram uso de antibióticos, de ventilação mecânica e de sonda nasoenteral em algum momento da internação. O tipo de terapia antifúngica não influenciou a mortalidade desses pacientes.(AU)

Justificación y Objetivos: Las infecciones fúngicas invasivas presentan una alta morbilidad y mortalidad en los pacientes hospitalizados, incluidos aquellos que utilizan la terapia adecuada. El objetivo fue evaluar la terapia antimicótica profiláctica y preventiva, las características clínicas, epidemiológicas y la mortalidad de pacientes ingresados en una sala de enfermedades infecciosas de un hospital público de alta complejidad en Uberlândia, Minas Gerais, Brasil. Métodos: Este es un estudio retrospectivo realizado en la sala de enfermedades infecciosas de un hospital universitario público en Brasil. Los datos recogidos de las historias clínicas se referían a pacientes hospitalizados en 2019 y 2020 y que utilizaban antifúngicos azoles (fluconazol, itraconazol o voriconazol), equinocandinas (anidulafungina) y polienos (anfotericina B). Resultados: Durante el período, 111 pacientes usaron uno o más antifúngicos. El tiempo de estancia hospitalaria (29,35 días, p= 0,0252), promedio de días de uso de antibacteriano (23,5 días; p=0,0164), SIDA (p=0,0397), uso de ventilación mecánica (VM; p<0,001) y uso de sonda nasoenteral (p<0,01) fueron variables que se relacionaron con el desenlace de muerte. La infección por hongos se confirmó en cultivo en 79 (71,2%) pacientes que usaban medicamentos antimicóticos. Los agentes fúngicos más frecuentes fueron Candida spp. (36; 32,4%) y Cryptococcus spp. (22; 19,8%), mostrando relación entre la infección por estos hongos y la mortalidad (p<0,05; 7,61 y 5,53, respectivamente). En cuanto a la terapia, 56 (50,4%) pacientes estaban en terapia empírica; 33 (29,7%) la utilizaron como terapia diana; y 22 (19,8%) la utilizaron como terapia preventiva. Conclusión: La mortalidad fue más frecuente entre los pacientes con mayor tiempo de internación, que tenían SIDA y que utilizaron antibióticos, ventilación mecánica y sonda nasoenteral en algún momento de la internación. El tipo de terapia antifúngica no influyó en la mortalidad de estos pacientes.(AU)

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.

Riesgo de mortalidad en infecciones invasoras por Fusarium spp en niños con enfermedades hemato-oncológicas: una revisión sistemática de la literatura / Risk of mortality in invasive infections by Fusarium spp in children with hematooncological diseases: a literature systematic review

INTRODUCCIÓN: Los estudios sobre la infección fúngica invasora (IFI) por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, son escasos, correspondiendo en general a series clínicas descriptas en forma retrospectiva, lo que dificulta conocer en profundidad sus características y evolución. OBJETIVO: Analizar la evolución fatal de la IFI causada por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, llevándose a cabo una revisión sistemática. MATERIAL Y MÉTODOS: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de PubMed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de EbscoHOST), SCI-EXPANDED y Scielo (a través de la WOS) y Scopus (a través de Scopus-Elsevier) y libre (mediante el motor Google) y revisando las citas de los artículos incluidos. RESULTADOS: Se rescataron 1.341 artículos, de los cuales se descartaron 931 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 11 estudios. Todos los estudios eran de nivel 4 (serie de casos). Se detectó una notoria heterogeneidad (p < 0,008) entre los mismos. La mediana de la frecuencia de muerte observada implicó a un tercio de los afectados (Md 33 %; Q1:22,7-Q4:75). CONCLUSIONES: La mortalidad por IFI por Fusarium spp fue alta en niños con patología hemato-oncológica, en especial en aquellos con neutropenia profunda y mala respuesta al tratamiento de su enfermedad de base

BACKGROUND: Studies on invasive fungal infection (IFI) by Fusarium spp in pediatric patients with hemato-oncological pathology are scarce and limited and a few series of cases described retrospectively, which makes it difficult to fully understand their characteristics and outcome. With the aim of analyzing the fatal evolution of these patients, this systematic review was carried out. METHODS: The literature search was performed up to March 23, 2023, in the main databases, as Medline (through PubMed), Embase (through Embase-Elsevier), The Cochrane Library (through Wiley), Cinahl (through EbscoHOST), SCI-EXPANDED and Scielo (through WOS) and Scopus (through Scopus-Elsevier) and free (through the Google engine) and reviewing the citations of the included articles. RESULTS: 1341 articles were retrieved, of which 931 were discarded for various reasons. By analyzing its full texts, 11 studies were finally included. It was observed that heterogeneity among them was relevant (p < 0.008). Median frequency of death involved one third of those affected (Md 33%; Q1:22,7-Q4:75). CONCLUSIONS: Mortality due to IFI due to Fusarium spp was high in children with hemato-oncological pathology, especially in those with severe neutropenia and poor response to treatment of their underlying disease.

Riesgo de mortalidad en infecciones invasivas por Mucor SPP. en niños con enfermedades hemato-oncológicas: revisión sistemática / Mortality risk of invasive Mucor spp. infections in children with cancer: A systematic review

Los estudios sobre la infección fúngica invasiva (IFI) por Mucor spp. en pacientes pediátricos con patología hematooncológica, son de baja solidez científica, lo que dificulta conocer en profundidad sus características y evolución. Con el objetivo de analizar la evolución fatal de esos pacientes, se llevó a cabo esta revisión sistemática (RS). Material y métodos: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de Pubmed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de Ebsco HOST), SCI-EXPANDED, SciELO (a través de la WOS) y Scopus (a través de Scopus-Elsevier), libre (mediante el motor Google) y revisando las citas de los artículos incluidos. Resultados: Se rescataron 1393 artículos, de los cuales se descartaron 1386 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 7 estudios. Todos los estudios eran series de casos (nivel 4). La mediana de la frecuencia de muerte observada fue de 36,6% (Q1 20% - Q347%). Conclusiones: Esta RS mostró en niños con patología hemato-oncológica, que la mortalidad por IFI por Mucor spp. alcanzó a casi un tercio de los pacientes (AU)

Studies on invasive fungal infection (IFI) by Mucor spp. in pediatric patients with cancer have a low level of evidence, which makes it difficult to elucidate its characteristics and progression. To analyze the fatal outcome of these patients, this systematic review (SR) was conducted. Material and methods: A literature search was carried out on March 23, 2023, in the following main databases (Medline (via Pubmed), Embase (via Embase-Elsevier), The Cochrane Library (via Wiley), Cinahl (via Ebsco HOST), SCI-EXPANDED, SciELO (via the WOS) and Scopus (via Scopus-Elsevier). Additionally, a complementary search was carried out using free search engines (such as Google) and by reviewing the references of the included articles. Results: A total of 1393 articles were retrieved, of which 1386 were excluded for various reasons. After a thorough analysis of the full-text articles, 7 studies were ultimately included in the review. All studies were case series (level 4). The median observed death rate was 36.6% (IQR, 20% - 47%). Conclusions: This SR showed that in children with hematological-oncological disease, mortality due to IFI by Mucor spp. affected almost one third of the patients (AU)

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.

Infección invasora por Trichosporon asahii en un niño con leucemia linfoblástica aguda / Invasive fungal infection by Trichosporon asahii in a pediatric patient with acute lymphoblastic leukemia: A case report and review of the literature

La enfermedad fúngica invasora (EFI) es una de las principales causas de morbimortalidad en los pacientes pediátricos inmunocom- prometidos. Los hongos que con mayor frecuencia causan EFI en este grupo de pacientes corresponden a especies de Candida y Aspergillus. Sin embargo, en los últimos años se ha descrito un aumento de patógenos no clásicos, tales como Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, entre otros. Se presenta un caso de EFI por Trichosporon asahii en un preescolar con una leucemia linfo- blástica aguda en quimioterapia de inducción. Además, se presenta una revisión actualizada de la literatura especializada, con énfasis en la importancia del diagnóstico precoz y el tratamiento antifúngico específico.

Invasive fungal disease (IFD) is one of the leading causes of morbidity and death among immunosuppressed pediatric patients. The fungi that most frequently cause IFD in this group of patients correspond to Candida and Aspergillus species, however, in recent years an increase in non-classical pathogens, such as Fusarium, Scedosporium, Mucorales, Cryptococcus, Trichosporon, among others. A case of invasive fungal disease caused by Trichosporon asahii is presented in a preschool patient with acute lymphoblastic leukemia in induction stage. This review highlights the importance of active search for pathogens in immunosuppressed patients, and proposes a specific treatment.

Infección por Aspergillus flavus y Rhizopus oryzae complex en paciente con diabetes mellitus / Infection due to Aspergillus flavus and Rhizopus oryzae complex in a patient with diabetes mellitus

La sinusitis micótica es una condición patológica que puede presentarse en pacientes con diabetes mellitus y estar asociada a una crisis hiperglucémica. Es una entidad agresiva con complicaciones locales que incluyen afectación de la órbita y el sistema nervioso central, y compromiso vascular. A pesar del tratamiento quirúrgico y antimicótico, la mortalidad es de hasta el 75 %. Se describe el caso de una paciente con diagnóstico de cetoacidosis diabética y signos de oftalmoplejía unilateral que llevaron al estudio con resonancia magnética del sistema nervioso central; se encontraron signos de sinusitis, meningitis y cerebritis. Los estudios microbiológicos iniciales fueron negativos, y los biomarcadores galactomanano sérico y el antígeno de Cryptococcus también fueron negativos. Tras el manejo quirúrgico, se llegó a la identificación de Aspergillus flavus y Rhizopus spp. en el tejido de los senos paranasales. La paciente recibió tratamiento con posaconazol y, tras dos meses de seguimiento, había presentado mejoría clínica. La infección fúngica dual y la infección por A. flavus son entidades poco frecuentes y de relevancia clínica, sin casos presentados previamente en nuestro país por lo que este corresponde a un caso de interés clínico.

Fungal sinusitis is a pathology that can occur in patients with diabetes mellitus and be associated with a hyperglycemic crisis. It is an aggressive entity with local complications that include involvement of the orbit or the central nervous system, and vascular involvement. Despite surgical and antifungal treatment, mortality raises up to 75%. We report the case of a female patient with a diagnosis of diabetic ketoacidosis and signs of unilateral ophthalmoplegia, which led to the study with magnetic resonance imaging of the central nervous system, finding signs of sinusitis, meningitis, and cerebritis. Initial microbiological studies were negative, and biomarkers such as serum galactomannan and Cryptococcus antigen were also negative. After surgical management and the identification of Aspergillus flavus and Rhizopus spp. in sinus tissue, the patient received treatment with posaconazole and after two months of follow-up she presented clinical improvement. Dual fungal infection and infection by A. flavus are uncommon and clinically relevant entities, with no cases previously reported in our country, therefore this corresponds to a case of clinical interest.

Un caso de paracoccidioidomicosis en laglándula suprarrenal bilateral / A case of paracoccidioidomycosisin the bilateral adrenal gland

La paracoccidioidomicosis es una micosis profunda. La afectación de la glándula suprarrenal es una forma de presentación rara que se asocia hasta un 10 a 15% de las insuficiencias supra renales y en algunas ocasiones puede ser la primera manifestación clínica de la patología. El objetivo del estudio es describir una presentación atípica de un paciente con diagnóstico de tumoración bilateral de la glándula supra renal, que en primer lugar se sospechó de un proceso tumoral de las glándulas supra renales y con la biopsia con punción guiada por ecografía se llegó al diagnóstico definitivo de paracocciodioidomicosis suprarrenal. Se realiza tratamiento con anfotericina B a una dosis de 50mg/día hasta una dosis acumulativa de 1500mg, con posterior seguimiento con itraconazol de 200 a 400mg/día por un periodo de 6 a 12 meses. Palabras Clave: paracoccidioidomicosis; glándulas suprarrenales; infecciones fúngicas invasoras

Paracoccidioidomycosis is aninvasive fungal infection.Involvement of the adrenal gland isa rare form of presentation that is associated with up to 10 to 15% of suprarenal insufficiencies and sometimes it can be the first clinical manifestation of the pathology. The objective of the study is to describean atypical presentation of a patient with a diagnosis of bilateral tumor of the suprarenal gland, that was suspected of a tumor process of the suprarenal glands and the definitive diagnosis with ultrasound-guided puncture biopsy was adrenal paracocciodioidomycosis.Treatment is carried out with amphotericin B at a dose of 50 mg/day up to a cumulative dose of 1500 mg, with subsequent follow-up with itraconazole of 200 to 400 mg/day for a period of 6 to 12 months. Key Words: paracoccidioidomycosis; adrenal glands; invasive fungal infections

Blinatumomab as bridging therapy in two children with B-cell acute lymphoblastic leukemia complicated by invasive fungal disease / 中国当代儿科杂志

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.

Infecciones fúngicas invasivas en niños hospitalizados en un centro de referencia de Uruguay / Invasive fungal infections in children hospitalized at a pediatric reference hospital in Uruguay / Infecções fúngicas invasivas em crianças internadas em um centro hospitalar de referência no Uruguai

Introducción: las infecciones fúngicas invasivas (IFI) son un problema de salud en creciente aumento. Objetivo: describir las características epidemiológicas, microbiológicas y clínicas de los menores de 15 años con IFI hospitalizados en el Hospital Pediátrico, Centro Hospitalario Pereira Rossell entre 2010- 2019. Metodología: estudio retrospectivo, mediante revisión de historias clínicas. Variables: edad, sexo, comorbilidades, factores de riesgo, clínica, patógenos, tratamiento y evolución. Resultados: se registraron 26 casos de IFI en 23 niños. La mediana de edad fue 8 años, de sexo femenino 17, con comorbilidades 17: infección por VIH 5, enfermedad hematooncológica 4. Todos presentaban factores de riesgo para IFI. Las manifestaciones clínicas de sospecha fueron: fiebre en 19, síntomas neurológicos 11, respiratorios 9, gastrointestinales 6, urinarios 2, sepsis/shock en 3. Los agentes identificados fueron: Candida spp en 14, Cryptococcus neoformans complex 8 y Aspergillus fumigatus complex 4. Tratamiento: se indicó fluconazol en 15, asociado a anfotericina B 11. Todas las infecciones por candida fueron sensibles a los azoles. Fallecieron 7 niños, la mediana de edad fue 1 año. En 4 se identificó Candida spp, Aspergillus fumigatus complex 2 y Cryptococcus neoformans complex 1. Conclusiones: las IFI son poco frecuentes, afectan en su mayoría a niños inmunocomprometidos asociando elevada mortalidad. El diagnóstico requiere alto índice de sospecha. Candida spp y Cryptococcus spp fueron los agentes más involucrados. El inicio precoz del tratamiento acorde a la susceptibilidad disponible se asocia a menor mortalidad.

Summary: Introduction: invasive fungal infections (IFI) are an increasing health problem. Objective: describe the epidemiological, microbiological and clinical characteristics of children under 15 years of age with IFI hospitalized at the Pereira Rossell Hospital Center between 2010-2019. Methodology: retrospective study, review of medical records. Variables: age, sex, comorbidities, risk factors, symptoms, pathogens, treatment and evolution. Results: 26 cases of IFI were recorded involving 23 children. Median age 8 years, female 17, comorbidities 17, HIV infection 5, hematological-oncological disease 4. All with risk factors. Suspicion symptoms: fever 19, neurological symptoms 11, respiratory 9, gastrointestinal 6, urinary 2, sepsis / shock 3. Identified agents: Candida spp 14, Cryptococcus neoformans complex 8 and Aspergillus fumigatus complex 4. Treatment: fluconazole 15, associated with amphotericin B 11. All candida infections were sensitive to azoles. 7 died, median age 1 year. In 4, Candida spp was isolated, Aspergillus fumigatus complex in 2 and Cryptococcus neoformans complex in 1. Conclusions: IFI are rare, mostly affecting immunocompromised children, associated with high mortality. The diagnosis requires a high index of suspicion. Candida spp and Cryptococcus spp were the most involved agents. Early treatment according to available susceptibility is associated with lower mortality.

Introdução: as infecções fúngicas invasivas (IFI) são um problema de saúde crescente. Objetivo: descrever as características epidemiológicas, microbiológicas e clínicas de crianças menores de 15 anos com IFI internadas no Centro Hospitalar Pereira Rossell entre 2010 e 2019. Metodologia: estudo retrospectivo, revisão de prontuários. Variáveis: idade, sexo, comorbidades, fatores de risco, sintomas, patógenos, tratamento e evolução. Resultados: foram registrados 26 casos de IFI em 23 crianças. Idade mediana 8 anos, sexo feminino 17, comorbidades 17, infecção por HIV 5, doença hemato-oncológica 4. Todos com fatores de risco. Suspeita clínica: febre 19, sintomas neurológicos 11, respiratórios 9, gastrointestinais 6, urinários 2, sepse/choque 3. Agentes identificados: Candida spp 14, Cryptococcus neoformans complexo 8 e Aspergillus fumigatus complexo 4. Tratamento: fluconazol 15, associado à anfotericina B 11. Todas as infecções por cândida foram sensíveis aos azóis. 7 morreram, idade média de 1 ano. Em 4 das crianças Cândida spp foi isolada, Aspergillus fumigatus complexo em 2 e Cryptococcus neoformans complexo em 1. Conclusões: IFIs são raras, afetando principalmente crianças imunocomprometidas, associadas a alta mortalidade. O diagnóstico requer alto índice de suspeita. Cândida spp e Cryptococcus spp são os agentes mais envolvidos. O tratamento precoce de acordo com a suscetibilidade disponível está associado a menor mortalidade.

Acurácia da detecção do antígeno galactomanana no soro para o diagnóstico precoce de aspergilose pulmonar invasiva: uma revisão rápida / Accuracy of serum galactomannan antigen detection for the early diagnosis of invasive pulmonary aspergillosis: a rapid review

Tecnologia: Detecção do antígeno galactomanana no soro. Contexto: A aspergilose pulmonar invasiva (API) é uma infecção fúngica oportunista de grande risco para pacientes imunocomprometidos. A detecção do antígeno galactomanana no soro por meio de um imunoensaio (ELISA) pode ser um teste não invasivo que auxilie no diagnóstico precoce da doença nestes pacientes. Objetivo: Avaliar a acurácia da detecção do antígeno galactomana no soro para o diagnóstico precoce de aspergilose pulmonar invasiva. Métodos: Revisão rápida sistematizada sobre acurácia de diagnóstico. As bases de dados utilizadas na pesquisa foram: PUBMED, EMBASE, SCOPUS, BVS e Cochrane Library. A avaliação da qualidade metodológica dos estudos incluídos foi realizada por meio da ferramenta AMSTAR-2. Resultados: Foram selecionadas três revisões sistemáticas que atendiam aos critérios de elegibilidade com as quais foi realizada uma análise descritiva dos dados encontrados. A avaliação da qualidade metodológica demonstrou que duas das revisões sistemáticas (RS) apresentaram qualidade criticamente baixa e uma das RS apresentou qualidade alta. Conclusão: A detecção da galactomanana sérica por ELISA pode ser um teste auxiliar no diagnóstico de API, entretanto, possui várias limitações e deve ser utilizado juntamente com outros critérios diagnósticos do consenso do EORTC/MSG. Novas pesquisas devem ser fomentadas para avaliar a utilização do teste no tempo do diagnóstico e no monitoramento da API

Technology: Detection of galactomannan antigen in serum. Background: Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection of serious risk for immunocompromised patients. Detection of galactomannan antigen in serum by immunoassay (ELISA) could be a noninvasive test that contributes to the early diagnosis of the disease in this group of patients. Objective: To evaluate the accuracy of serum galactomannan antigen detection for the early diagnosis of invasive pulmonary aspergillosis. Methods: Rapid review of diagnostic accuracy. Databases used in the search were: PUBMED, EMBASE, SCOPUS, BVS, and Cochrane Library. The methodological quality of the included studies was assessed using the AMSTAR-2 tool. Results: Three systematic reviews that satisfied the eligibility criteria were selected, and a descriptive analysis of the data found was performed. The methodological quality assessment showed that two of the systematic reviews (SR) presented critically low quality, and one of the SR presented high quality. Conclusion: Detection of serum galactomannan by ELISA may be a valuable test for diagnosing IPA; however, it has a series of limitations and should be used in conjunction with other diagnostic criteria of the EORTC/MSG consensus. Further research should be encouraged to evaluate the use of this assay, considering the time to diagnosis and IPA monitoring

COVID-19 associated rhinomaxillary mucormycosis: a case series and review of literature

During COVID-19 pandemic, fulminant deep fungal infection started emerging in India, known as Mucormycosis. This type of mucormycosis was termed as COVID-19 associated mucormycosis (CAM). These patients had previous history of COVID-19 infection. Such cases were mainly reported in immunocompromised patients such as patients with poorly controlled diabetes and chronic renal diseases etc. Rhinomaxillary mucormycosis is an aggressive, fulminant, fatal deep fungal infection of head and neck region. Early diagnosis and prompt treatment can reduce the mortality and morbidity associated with the disease; hence we present case series of rhinomaxillary mucormycosis to create awareness amongst dental surgeons

Evaluation of interactions of silibinin with the proteins ALS3 and SAP5 against Candida albicans / Avaliação das interações da silibinina com as proteínas ALS3 e SAP5 contra Candida albicans

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.

Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.

Infección fúngica invasiva por Saprochaete capitata en un niño con aplasia medular / Invasive fungal infection by Saprochaete capitata in a child with bone marrow aplasia

RESUMEN Saprochaete capitata es una causa rara de infección fúngica invasiva en pacientes inmunocomprometidos con alta mortalidad y resistencia antifúngica. Presentamos el caso de un niño de cinco años con diagnóstico de aplasia medular, sometido a trasplante de progenitores hematopoyéticos (TPH), que cursó con neutropenia febril persistente, dolor abdominal intenso, aparición de lesiones maculopapulares en piel y deterioro de la función renal. Se identificó la presencia de S. capitata, en hemocultivos transcatéter venoso central. Esta infección fúngica invasiva resulta ser rara, pero emergente y potencialmente mortal, en pacientes con neutropenia febril persistente y uso prolongado de dispositivos invasivos intravasculares como catéter venoso central.

ABSTRACT Saprochaete capitata is a rare cause of invasive fungal infection in immunocompromised patients with high mortality and antifungal resistance. We present the case of a 5-year-old boy with bone marrow aplasia, who underwent hematopoietic stem cell transplantation (HSCT) and presented persistent febrile neutropenia, abdominal pain, appearance of maculopapular lesions on the skin, and impaired renal function. The presence of S. capitata was identified by blood culture from a central venous catheter. This invasive fungal infection is rare but emergent and life-threatening, especially in immunocompromised patients with persistent febrile neutropenia and prolonged use of invasive devices such as central venous catheters.

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.

Evaluación de la dosificación de voriconazol intravenoso tres veces al día vs dos veces al día para el tratamiento de aspergilosis invasora en niños inmunocomprometidos: monitorización terapéutica y seguridad / Evaluation dosing intravenous voriconazole three times a day vs twice daily for the treatment of invasive aspergillosis in immunocompromised children: therapeutic drugs monitoring and safety

INTRODUCCIÓN: Voriconazol es el antifúngico de elección para el tratamiento de la aspergilosis invasora (AI). Concentraciones plasmáticas (CPs) > 1 μg/mL se han asociado a mejores resultados terapéuticos, las que no siempre se alcanzan durante el tratamiento en niños inmunocomprometidos. Dada la necesidad de iniciar una terapia precoz y efectiva de la infección, es relevante establecer el régimen de administración de voriconazol que se asocie con CPs óptimas en esta población. OBJETIVO: Comparar las CPs y seguridad de voriconazol intravenoso (IV), dosificado BID y TID en niños inmunocomprometidos con indicación de tratamiento antifúngico. MÉTODO: Estudio observacional retrospectivo de enero de 2015 a julio de 2018 en un hospital pediátrico de alta complejidad de Santiago de Chile, en pacientes de 0 a 17 años que recibieron tratamiento con voriconazol IV. Se excluyeron aquellos con terapia de reemplazo renal, falla hepática y/o falla renal. Se compararon las CPs valles entre un grupo con régimen de dosificación BID y otro grupo con administración TID. Se evaluaron las reacciones adversas en ambos grupos. RESULTADOS: Se obtuvieron 137 CPs valles en 76 niños, con una mediana de edad de 9 años (0-17 años) en el grupo BID y 9 años (0-16 años) en el grupo TID, con una mediana de peso de 27 kg (6-83 kg) y 28 kg (9,3-60 kg), respectivamente. Resultados: Pacientes 1 gg/mL en comparación con la administración BID (p = 0,001). Se reportaron ocho reacciones adversas, principalmente fotofobia, sin encontrarse diferencias significativas entre grupo BID y TID. CONCLUSIÓN: Dosificaciones TID están asociadas a una mayor probabilidad de obtener una adecuada exposición a voriconazol en pacientes < 12 años en comparación a dosificaciones BID, con baja frecuencia de reacciones adversas.

BACKGROUND: Voriconazole is the antifungal of choice for the treatment of invasive aspergillosis (IA). Plasma concentrations (PCs) > 1 μg / mL llave been associated with better therapeutic results which have not always been achieved during treatment in immunocompromised children. In the necessity to initiate early and effective therapy for the infection, it is relevant to establish the voriconazole administration regimen that is associated with optimal PCs in this population. AIM: To compare the PC and safety of intravenous (IV) voriconazole, dosed BID and TID in immunocompromised children with indication of antifungal treatment. METHOD: Retrospective observational study since January 2015 until July 2018 in a highly complex pediatric hospital in Santiago of Chile, in patients aged 0 to 17 years who received treatment with IV voriconazole. Those with renal replacement therapy, liver failure and / or renal failure were excluded. Trough PCs were compared between a group with BID dosing regimen versus another group with TID administration. Adverse reactions were evaluated in both groups. RESULTS: 137 trough PCs were obtained in 76 children, with a median age of 9 years (0-17 years) in the BID group and 9 years (0-16) in the TID group with a median weight of 27 kg (6-83 kg) and 28 kg (9.3-60 kg), respectively. Patients 1 gg/mL compared to BID administration (p = 0.001). Eight adverse reactions were reported, mainly photophobia, with no significant difference found between the BID and TID groups. CONCLUSION: TID dosages are associated with a greater probability of obtaining adequate exposure to voriconazole in patients < 12 years old compared to BID dosages, with a low frequency of adverse reactions.

Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases

Abstract Introduction Invasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential. Objectives The aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses. Methods This was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality. Results A total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10 cells/μL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia. Conclusion Both confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.

Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.@*METHODS@#The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.@*RESULTS@#Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.@*CONCLUSION@#The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.

Consensus on diagnosis and treatment of invasive fungal infection in patients with severe liver disease / 中华肝脏病杂志

The prognosis of severe liver disease combined with invasive fungal infection (IFI) is poor, and the clinical manifestations are often atypical. Moreover, most of the antifungal drugs are metabolized in the liver, with severe toxicities and side effects, making clinical diagnosis and treatment difficult. The Professional Committee for Hepatology, the Chinese Research Hospital Association and the Hepatology Branch of China Medical Association organized relevant experts to formulate an expert consensus based on the characteristics of patients with severe liver disease combined with IFI, in order to provide reference for medical personnel in making decisions on the diagnosis and treatment.