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PURPOSE: Patients with hematologic malignancies (HM) are at high risk of invasive lung fungal infections (ILFI). To describe the main characteristics, treatment, and outcomes for five years in adult patients with HM and fungal pneumonia. METHODS: We conducted a retrospective study at Instituto Nacional de Cancerología (INCan), a referral tertiary care oncology hospital with 135 beds in Mexico City, Mexico. We included all cases of fungal pneumonia in patients with HM from January 1, 2017, to December 31, 2022. Cases were classified as proven, probable, and possible according to EORTC/MSG criteria 2021. RESULTS: Two hundred ten patients were included; the mean age was 40 years. The most frequent HM was acute lymphoblastic leukemia (n = 74) and acute myeloid leukemia (n = 68). One hundred forty patients (66.7%) had severe neutropenia for a median of 16 days. All patients had a CT thorax scan; in 132 (62.9%), multiple nodules were documented. Serum galactomannan (GM) was positive in 21/192 (10.9%) and bronchoalveolar lavage in 9/36 (25%). Fifty-three patients (25.2%) died in the first month. In the multivariate analysis for mortality in the first 30 days, hypoalbuminemia, shock, possible ILFI, and inappropriate antifungal treatment were statistically associated. CONCLUSIONS: In high-risk HM patients, CT thorax scan and GM help diagnose ILFI. An appropriate antifungal improves mortality.
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Neoplasias Hematológicas , Humanos , Adulto , Masculino , Estudios Retrospectivos , Femenino , Neoplasias Hematológicas/complicaciones , Persona de Mediana Edad , Enfermedades Pulmonares Fúngicas/microbiología , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Enfermedades Pulmonares Fúngicas/complicaciones , Adulto Joven , Antifúngicos/uso terapéutico , México/epidemiología , Anciano , Neumonía/microbiología , Adolescente , Galactosa/análogos & derivados , Mananos/sangre , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/mortalidad , Infecciones Fúngicas Invasoras/diagnósticoRESUMEN
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)
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Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas Invasoras/mortalidad , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/epidemiología , AntifúngicosRESUMEN
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.
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Infecciones Fúngicas Invasoras/epidemiología , Neoplasias/complicaciones , Chile/epidemiología , Estudios Retrospectivos , Estudio Multicéntrico , Quimioprevención/métodos , Neutropenia Febril/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Hongos/aislamiento & purificación , Hospitales Públicos/estadística & datos numéricos , Anemia Aplásica/epidemiología , Antifúngicos/administración & dosificaciónRESUMEN
Systemic infections caused by rare yeasts are increasing given the rise in immunocompromised or seriously ill patients. Even though globally, the clinical significance of these emerging opportunistic yeasts is increasingly being recognized, less is known about the epidemiology of rare yeasts in Latin America. This review collects, analyzes, and contributes demographic and clinical data from 495 cases of infection caused by rare yeasts in the region. Among all cases, 32 species of rare yeasts, distributed in 12 genera, have been reported in 8 Latin American countries, with Trichosporon asahii (49.5%), Rhodotorula mucilaginosa (11.1%), and Saccharomyces cerevisiae (7.8%) the most common species found. Patients were mostly male (58.3%), from neonates to 84 years of age. Statistically, surgery and antibiotic use were associated with higher rates of Trichosporon infections, while central venous catheter, leukemia, and cancer were associated with higher rates of Rhodotorula infections. From all cases, fungemia was the predominant diagnosis (50.3%). Patients were mostly treated with amphotericin B (58.7%). Crude mortality was 40.8%, with a higher risk of death from fungemia and T. asahii infections. Culture was the main diagnostic methodology. Antifungal resistance to one or more drugs was reported in various species of rare yeasts.
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Background: Invasive Fungal Infections (IFI) are emergent complications of COVID-19. In this study, we aim to describe the prevalence, related factors, and outcomes of IFI in critical COVID-19 patients. Methods: We conducted a nested case-control study of all COVID-19 patients in the intensive care unit (ICU) who developed any IFI and matched age and sex controls for comparison (1:1) to evaluate IFI-related factors. Descriptive and comparative analyses were made, and the risk factors for IFI were compared versus controls. Results: We found an overall IFI prevalence of 9.3% in COVID-19 patients in the ICU, 5.6% in COVID-19-associated pulmonary aspergillosis (CAPA), and 2.5% in invasive candidiasis (IC). IFI patients had higher SOFA scores, increased frequency of vasopressor use, myocardial injury, and more empirical antibiotic use. CAPA was classified as possible in 68% and 32% as probable by ECMM/ISHAM consensus criteria, and 57.5% of mortality was found. Candidemia was more frequent for C. parapsilosis Fluconazole resistant outbreak early in the pandemic, with a mortality of 28%. Factors related to IFI in multivariable analysis were SOFA score > 2 (aOR 5.1, 95% CI 1.5-16.8, p = 0.007) and empiric antibiotics for COVID-19 (aOR 30, 95% CI 10.2-87.6, p = <0.01). Conclusions: We found a 9.3% prevalence of IFIs in critically ill patients with COVID-19 in a single center in Mexico; factors related to IFI were associated with higher SOFA scores and empiric antibiotic use for COVID-19. CAPA is the most frequent type of IFI. We did not find a mortality difference.
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Invasive fungal infections (IFI) are responsible for a large number of annual deaths. Most cases are closely related to patients in a state of immunosuppression, as is the case of patients undergoing chemotherapy. Cancer patients are severely affected by the worrisome proportions that an IFI can take during cancer progression, especially in an already immunologically and metabolically impaired patient. There is scarce knowledge about strategies to mitigate cancer progression in these cases, beyond conventional treatment with antifungal drugs with a narrow therapeutic range. However, in recent years, ample evidence has surfaced describing the possible interferences that IFI may have both on the progression of pre-existing cancers and in the induction of newly transformed cells. The leading gambit for modulation of tumor progression comes from the ability of fungal virulence factors to modulate the host's immune system, since they are found in considerable concentrations in the tumor microenvironment during infection. In this context, cryptococcosis is of particular concern, since the main virulence factor of the pathogenic yeast is its polysaccharide capsule, which carries constituents with high immunomodulatory properties and cytotoxic potential. Therefore, we open a discussion on what has already been described regarding the progression of cryptococcosis in the context of cancer progression, and the possible implications that fungal glycan structures may take in both cancer development and progression.
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Criptococosis , Cryptococcus neoformans , Neoplasias , Humanos , Criptococosis/microbiología , Polisacáridos , Antifúngicos , Factores de Virulencia , Microambiente TumoralRESUMEN
Chimeric antigen receptors (CARs) redirect T cells to recognize a specific target. CAR components play a pivotal role in antigen specificity, structure stability, expression on cell surface, and induction of cellular activation, which together determine the success of CAR T-cell therapy. CAR products targeting B-cell lymphoma encouraged the development of new CAR applications beyond cancer. For example, our group developed a CAR to specifically target glucuronoxylomannan (GXM) in the capsule of Cryptococcus species, called GXMR-CAR or GXMR-IgG4-28ζ. Cryptococcus are fungi that cause the life-threatening disease cryptococcosis, and GXMR-IgG4-28ζ redirected T cells to target yeast and titan cell forms of Cryptococcus spp. Here, we replaced the IgG4-hinge and CD28-transmembrane domains from GXMR-CAR with a CD8α molecule as the hinge/transmembrane and used CD28 or 4-1BB molecules as co-stimulatory domains, creating GXMR-8-28ζ and GXMR-8-BBζ, respectively. Jurkat cells expressing GXMR-CAR containing CD8α as the hinge/transmembrane improved the CAR expression and induced a tonic signaling. GXMR-8-28ζ and GXMR-8-BBζ induced high levels of IL-2 and up-regulation of CD69 expression in the presence of reference strains of C. neoformans and C. gattii. Moreover, GXMR-8-28ζ and GXMR-8-BBζ showed increased strength in response to incubation with clinical isolates of Cryptococcuss spp., and 4-1BB co-stimulatory domain triggered a more pronounced cellular activation. Dasatinib, a tyrosine kinase inhibitor, attenuated the GXMR-CAR signaling cascade's engagement in the presence or absence of its ligand. This study optimized novel second-generation GXMR-CARs containing the CD8-hinge/transmembrane domain that improved CAR expression, antigen recognition, and signal strength in T-cell activation.
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Cryptococcus , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Humanos , Antígenos CD28/metabolismo , Cryptococcus/inmunología , Cryptococcus/metabolismo , Inmunoglobulina G , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores Quiméricos de Antígenos/química , Receptores Quiméricos de Antígenos/metabolismo , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto , Polisacáridos/química , Polisacáridos/inmunología , Criptococosis/inmunología , Criptococosis/terapiaRESUMEN
Background and Purpose: Disseminated fusariosis is an opportunistic infection caused by the hyaline fungus Fusarium spp. and occurs mainly in patients with leukemia. Case report: Two cases of disseminated fusariosis in pediatric patients are presented. Profound and prolonged neutropenia, fever, myalgia, and skin lesions in the legs were present in two girls with leukemia undergoing chemotherapy. In the first case, infection by Fusarium spp. was confirmed by anatomopathological findings, pathogen isolation, and polymerase chain reaction. In the second case, Fusarium solani infection was confirmed by mass spectrometry using blood cultures and skin lesion samples. Conclusion: It is important to consider disseminated fusariosis in high-risk patients who present with profound and prolonged neutropenia and persistent fever that does not resolve after broad-spectrum antibiotics to initiate antifungal therapy in a timely manner.
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Magnusiomyces capitatus (also denominated "Geotrichum capitatum" and "the teleomorph stage of Saprochaete capitata") mainly affects immunocompromised patients with hematological malignancies in rare cases of invasive fungal infections (IFIs). Few cases have been reported for pediatric patients with acute lymphoblastic leukemia (ALL), in part because conventional diagnostic methods do not consistently detect M. capitatus in infections. The current contribution describes a systemic infection in a 15-year-old female diagnosed with ALL. She arrived at the Children's Hospital of Mexico City with a fever and neutropenia and developed symptoms of septic shock 4 days later. M. capitatus ENCB-HI-834, the causal agent, was isolated from the patient's blood, urine, bile, and peritoneal fluid samples. It was identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and a phylogenetic reconstruction using internal transcribed spacer (ITS) and 28S ribosomal sequences. The phylogenetic sequence of M. capitatus ENCB-HI-834 clustered with other M. capitatus-type strains with a 100% identity. In vitro antifungal testing, conducted with the Sensititre YeastOne susceptibility system, found the following minimum inhibitory concentration (MIC) values (µg/mL): posaconazole 0.25, amphotericin B 1.0, fluconazole > 8.0, itraconazole 0.25, ketoconazole 0.5, 5-flucytosine ≤ 0.06, voriconazole 0.25, and caspofungin > 16.0. No clinical breakpoints have been defined for M. capitatus. This is the first clinical case reported in Mexico of an IFI caused by M. capitatus in a pediatric patient with ALL. It emphasizes the importance of close monitoring for a timely and accurate diagnosis of neutropenia-related IFIs to determine the proper treatment with antibiotics, antifungals, and chemotherapy for instance including children with ALL.
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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.
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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.
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.
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COVID-19 , Cetoacidosis Diabética , Infecciones Fúngicas Invasoras , Mucormicosis , Argentina/epidemiología , Humanos , Mucormicosis/diagnóstico , Mucormicosis/tratamiento farmacológico , Mucormicosis/epidemiología , SARS-CoV-2RESUMEN
Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients. LAY SUMMARY: Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.
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Neoplasias Hematológicas , Infecciones Fúngicas Invasoras , Infecciones del Sistema Respiratorio , Animales , Antifúngicos/uso terapéutico , Geotrichum , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/veterinaria , Humanos , Huésped Inmunocomprometido , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/veterinaria , Masculino , México/epidemiología , Derivación y Consulta , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/veterinariaRESUMEN
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.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Fusariosis , Infecciones Fúngicas Invasoras , Enfermedades Hematológicas , Sinusitis , Neutropenia Febril , FusariumRESUMEN
Trichosporon yeasts are classical agents of superficial mycoses, and they are ranked as the first to second predominant basidiomycetous yeast able to cause invasive infections. The clinical presentation of Trichosporon infections varies with the affected anatomical site, with fungaemia present in the majority of invasive trichosporonosis cases. Only a limited number of antifungal compounds can be used to treat Trichosporon infections. Azoles are the first choice due to their intrinsic resistance to echinocandins. Better laboratory methods and up-to-date databases of commercial platforms are required to improve identification, susceptibility testing and surveillance of this potentially threating infection.
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Basidiomycota , Trichosporon , Tricosporonosis , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Equinocandinas , Tricosporonosis/diagnóstico , Tricosporonosis/tratamiento farmacológico , Tricosporonosis/microbiologíaRESUMEN
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 10cells/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.
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BACKGROUND: COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. METHODOLOGY: A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. RESULTS: During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. CONCLUSION: A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.
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Aspergilosis , COVID-19 , Candidemia , Coinfección , Criptococosis , Adulto , Anciano , Aspergilosis/epidemiología , Brasil/epidemiología , COVID-19/epidemiología , Candidemia/epidemiología , Coinfección/epidemiología , Criptococosis/epidemiología , Femenino , Hongos , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Derivación y Consulta , Estudios RetrospectivosRESUMEN
We present the case of a man with acute lymphoblastic leukemia and prolonged profound neutropenia, who developed an invasive infection by Fusarium graminearum, acquired via non-cutaneous entry, with gastrointestinal symptoms, sigmoid perforation and liver abscesses due to portal dissemination. The etiologic agent was identified using the 18S-ITS1-5.8S-ITS2-28S rRNA sequence gene, from a liver biopsy. The infection was resolved with surgical drainage and antifungal treatment based on voriconazole. As far as we know, there are no previous reports in the literature of cases of human infection due to Fusarium graminearum.
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Resumen Objetivo: Comparar los resultados obtenidos de diferentes sistemas de identificación de C. auris. Métodos: Análisis descriptivo con datos recopilados durante 2016-19 mediante la vigilancia nacional. Se evaluaron los resultados generados por los sistemas MicroScan, Phoenix BD, VITEK 2 y MALDI-TOF MS de instituciones hospitalarias de 843 aislamientos clínicos sospechosos de C. auris remitidos al INS y se compararon con los resultados generados de confirmación a través de MALDI- TOF MS (Bruker Daltonics) o PCR. Resultados: De los 843 aislamientos clínicos remitidos al INS, el 81,7% fueron confirmados como C. auris mediante MALDI- TOF MS o PCR en el INS y el resto, 18,3%, fueron identificados como otras especies de Candida spp. Las identificaciones correctas enviadas por los laboratorios representaron el 42,4%. MicroScan identificó C. auris principalmente como C. haemulonii, C. guilliermondii, C. albicans y C. famata; Phoenix BD, VITEK 2 y MALDI-TOF MS identificó C. auris como C. haemulonii. Discusión: Estudios señalan que C. auris exhibe una estrecha relación filogenética con C. haemulonii. Las identificaciones discrepantes pueden darse debido a que las bases de datos de los sistemas de diagnóstico son limitadas para este patógeno. Las deficiencias de los sistemas comerciales para la identificación de C. auris deben ser complementados con otros sistemas como MALDI-TOF MS o pruebas moleculares.
Abstract Objective: To compare the identification results obtained by different identification systems of C. auris isolates. Methods: A descriptive study with data collected during the years 2016-19 through surveillance. The results generated by the MicroScan, Phoenix BD, VITEK 2 and MALDI-TOF MS systems of 843 clinical isolates of C. auris submitted to the INS were evaluated and compared with the results generated from confirmation through MALDI-TOF MS (Bruker Daltonics) or PCR. Results: Out of 843 clinical isolates submitted to the INS, 81.7% were confirmed as C. auris by MALDITOF MS or PCR in the INS and the rest, 18.3%, were identified as other species of Candida spp. The correct identifications sent by the laboratories was 42.4%. MicroScan identified C. auris as C. haemulonii, C. guilliermondii, C. albicans and C. famata; Phoenix BD, VITEK 2 and MALDI-TOF MS identified C. auris as C. haemulonii. Discussion: Studies indicate that C. auris exhibits a close phylogenetic relationship with C. haemulonii. In addition, discrepant identifications may occur because the databases of diagnostic systems are limited with reference to this pathogen. The deficiencies of commercial systems for the identification of C. auris must be complemented with other systems such as MALDI-TOF MS or molecular tests.
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Humanos , Femenino , Candida , Vigilancia en Desastres , Diagnóstico , Laboratorios , Reacción en Cadena de la Polimerasa , Epidemiología Descriptiva , Colombia , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Técnicas de Diagnóstico Molecular , ÁlcalisRESUMEN
Resumen Candida auris es una levadura multi-resistente emergente con rápida diseminación mundial. Desde el primer reporte el 2009, varios aislados a través de los cinco continentes han sido identificados como agentes de infecciones asociadas a la atención en salud. Brotes independientes y simultáneos por C. auris se han vuelto prioridad para la comunidad hospitalaria y científica. Además, los errores en identificación y los perfiles de multi-resistencia, raramente observados para otras especies de Candida, resultan en una difícil erradicación y fallas terapéuticas frecuentes en infecciones por C. auris. Presentamos el primer aislamiento de una cepa de C. auris en un hospital en Santiago, en un paciente proveniente de la India, que fue admitido para tratamiento de su pie diabético. La cepa fue recuperada de un cultivo de tejido e identificada por VITEK® 2 Compact. La identificación de C. auris fue confirmada por MALDI-TOF MS y secuenciación. El aislado fue resistente a fluconazol y susceptible a anfotericina y caspofungina, según puntos de corte recomendados por el CDC. La emergencia de C. auris es alarmante debido a que el modo de transmisión dentro del ambiente hospitalario no es claro y probablemente es multifactorial.
Candida auris is an emerging multi-drug-resistant fungus that is rapidly spreading worldwide. Since the first reports in 2009, many isolates across five continents have been identified as agents of hospital-associated infections. Independent and simultaneous outbreaks of C. auris are becoming a major concern for healthcare and scientific community. Moreover, laboratory misidentification and multi-drug-resistant profiles, rarely observed for other non-albicans Candida species, result in difficult eradication and frequent therapeutic failures of C. auris infections. In this article we present the first case of isolation of a strain of C. auris at a hospital in Santiago, in a patient coming from India, who was admitted for treatment of diabetic foot complications. The strain was recovered from a tissue culture and identified by VITEK® 2 Compact. The accurate identification of C. auris was confirmed by means of MALDI-TOF MS and DNA sequence analysis. The isolate was resistant to fluconazole, retaining only susceptibility to amphotericin and caspofungin with MIC breakpoints recommended by CDC. The emergence of C. auris is alarming because the mode of transmission within the healthcare environment is not clear and is likely to be multifactorial.
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Humanos , Candida/genética , Candidiasis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Chile , Antifúngicos/uso terapéutico , Antifúngicos/farmacologíaRESUMEN
Introducción: Las infecciones fúngicas invasivas son producidas casi universalmente por Candida o Aspergillus, pero se identifican otros hongos que requieren abordajes individualizados, principalmente en pacientes inmunocomprometidos. El micetoma es una enfermedad granulomatosa crónica, generalmente limitada a la piel y al tejido subcutáneo; sin embargo, existen localizaciones como la torácica y abdominal, consideradas de mal pronóstico, debido a una diseminación visceral. Objetivo: Mostrar otra alternativa de diseminación visceral de un micetoma, en un paciente que fue sometido a un trasplante renal. Caso clínico: Paciente que se sometió a un trasplante de riñón de un donante de cadáver. Se le diagnosticó micetoma por Candida albicans en el brazo derecho y daño pulmonary. Tuvo buena respuesta al tratamiento. Comentarios: Las infecciones fúngicas invasivas son cada vez más frecuentes en la práctica clínica, especialmente en pacientes inmunodeprimidos. En la actualidad, hay nuevos medicamentos disponibles que son útiles para el tratamiento de estos pacientes, pero el pronóstico continúa siendo desalentador en muchos casos. Estas entidades tienen la capacidad de afectar a diferentes órganos, lo cual condiciona un compromiso grave para el paciente(AU)
Introduction: Invasive fungal infections are almost universally produced by Candida or Aspergillus, but other fungi are identified that require individualized approaches, mainly in immunocompromised patients. Mycetoma is a chronic granulomatous disease, usually limited to the skin and subcutaneous tissue; however, there are localizations such as the thoracic and abdominal, considered of poor prognosis due to a visceral dissemination. Objective: To show another alternative of visceral dissemination of a mycetoma in a patient who underwent a kidney transplant. Clinical case: We report the case of a female patient who underwent a kidney transplant from a cadaveric donor. She had a diagnosis of Candida albicans mycetoma in the right arm and lung damage. She had a good response to treatment. Comments: Invasive fungal infections are becoming more frequent in clinical practice, especially affecting immunosuppressed patients. At present, new drugs are available that are useful in the treatment of these patients, but the prognosis continues to be discouraging in many cases. These infections have the capacity to affect different organs, which determines a serious problem for the patient(AU)