Epidemiological indicators and predictors of lethality associated with fungal infections in a NICU: a historical series

Abstract Objectives: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. Methods: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. Results: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). Conclusion: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.

Fatal co-infection by multiple pathogens in an indigenous woman with autoimmune hemolytic anemia and tuberculosis: a case report.

BACKGROUND: Tuberculosis (TB), one of the leading causes of death worldwide, has a higher incidence among indigenous people. Albeit uncommon, autoimmune hemolytic anemia (AIHA) has been deemed a risk condition to develop mycobacterial infection, as a result of the immunosuppressive treatments. TB, in turn, can be a predisposing factor for secondary infections. CASE PRESENTATION: Here we present a case of a 28-year-old indigenous woman from Colombia, previously diagnosed with AIHA and pulmonary TB. Despite various treatments, therapies and medical interventions, the patient died after severe medullary aplasia of multiple causes, including secondary myelotoxicity by immunosuppressive therapy and secondary disseminated infections, underlining infection by Staphylococcus aureus, Klebsiella pneumoniae and Candida glabrata, which were identified as drug-resistant microorganisms. Together, this led to significant clinical complications. Invasive aspergillosis was diagnosed at autopsy. CONCLUSIONS: This report presents a rarely finding of AIHA followed by TB, and highlights the great challenges of dealing with co-infections, particularly by drug resistant pathogens. It also aims to spur governments and public health authorities to focus attention in the prevention, screening and management of TB, especially among vulnerable communities, such as indigenous people.

Fungal-associated pneumonia in patients with hematological malignancies.

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.

Candida Non-albicans and Non-auris Causing Invasive Candidiasis in a Fourth-Level Hospital in Colombia: Epidemiology, Antifungal Susceptibility, and Genetic Diversity.

Increasingly common and associated with healthcare settings, Candida infections are very important, since some species of this genus can develop antifungal resistance. We contribute data on the epidemiology, antifungal susceptibility, and genetic diversity of Candida non-albicans and non-auris affecting critically ill patients in a fourth-level hospital in Colombia. Ninety-seven isolates causing invasive infections, identified by conventional methods over 18 months, were studied. Data from patients affected by these yeasts, including sex, age, comorbidities, treatment, and outcome, were analysed. The antifungal susceptibility of the isolates was determined, and the ribosomal DNA was sequenced. Candida parapsilosis, Candida tropicalis, Candida glabrata, Candida dubliniensis, and Candida guilliermondii caused 48.5% of all cases of invasive candidiasis. The species were mainly recovered from blood (50%). Patients were mostly men (53.4%), between 18 days and 93 years old, hospitalized in the ICU (70.7%). Overall mortality was 46.6%, but patients in the ICU, using antibiotics, with diabetes mellitus, or with C. glabrata infections were more likely to die. Resistant isolates were identified in C. parapsilosis, C. tropicalis, and C. glabrata. This study provides epidemiological data for the surveillance of emerging Candida species, highlighting their clinical impact, as well as the emergence of antifungal resistance and clonal dispersal.

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)

COVID-19 associated with cryptococcosis: a scoping review.

Background: There is growing evidence of fungal infections associated with COVID-19. The development of cryptococcosis in these patients has been infrequently reported. However, it can be life-threatening. Objective: To identify cases of COVID-19 patients who developed cryptococcosis and to compare baseline characteristics and management between those who survived and those who died. Methods: We conducted a scoping review using PubMed, Scopus, Web of Science, and Embase to identify studies that reported patients with COVID-19 and cryptococcosis. No language restriction was applied. Single case reports, case series, and original articles were included. It is important to note that 'n' refers to the total number of individuals with the specified variable. Results: A total of 58 studies were included. Among these studies, 51 included individual patient data, detailing information on a total of 65 patients, whereas eight studies reported the proportion of cryptococcosis in COVID-19 patients. One study provided both individual and aggregate case information. From individual patient data, the majority were male (73.9%; n = 48) with a median age of 60 years (range: 53-70). Severe COVID-19 and multiple comorbidities, led by arterial hypertension and diabetes mellitus, were frequently reported, but few had classic immunosuppression factors. On the other hand, HIV status, either negative or positive, was reported in just over half of the patients (61.5%; n = 40). Most were admitted to the intensive care unit (ICU) (58.5%; n = 31), received mechanical ventilation (MV) (50.0%; n = 26), and developed disseminated cryptococcosis (55.4%; n = 36). Secondary infection, mainly bacterial, was reported in 19 patients (29.2%). Mortality was 47.7% (n = 31). Of the studies that reported the proportion of cryptococcosis in COVID-19 cases, the majority were descriptive studies published as conference abstracts. Conclusion: Cryptococcosis in COVID-19 patients has been reported more frequently. However, it is still not as common as other fungal infections associated with COVID-19. Few patients have some classic immunosuppression factors. The factors associated with mortality were male sex, age, ICU admission, MV, secondary infections, and lymphopenia.

Maxillary mucormycosis and aspergillosis in post-COVID-19 patients in Mexico: A case series.

BACKGROUND: Fungal infections, during or as a consequence of SARS-CoV-2 infection, associated with uncontrolled diabetes mellitus and indiscriminate use of corticosteroids have been reported. In the jaw, mostly mucormycosis has been diagnosed in hospitals. METHODS: A retrospective, cross-sectional, descriptive study of the clinical, imaging, and histopathologic characteristics of maxillary invasive fungal infection in post-COVID-19 patients diagnosed in a private non-hospital oral pathology service in Mexico during 2020-2022 was conducted. RESULTS: We found 20 cases of maxillary invasive fungal infections in post-COVID-19 patients, 75% including a diagnosis of mucormycosis and 25% diagnosed as probable aspergillosis. The most common signs and symptoms were exposed necrotic bone followed by tooth mobility, discharge, and pain. On imaging, unilateral maxillary sinus involvement was observed in 6 cases (30%), and bilateral maxillary sinus involvement was observed in 3 cases (15%). CONCLUSIONS: It is essential to consider the association of osteonecrosis of the jaw in post-COVID-19 patients, with aspergillosis, not only mucormycosis, for early diagnosis and appropriate treatment.

Epidemiological indicators and predictors of lethality associated with fungal infections in a NICU: a historical series.

OBJECTIVES: Fungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. METHODS: This study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. RESULTS: Thirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). CONCLUSION: These findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.

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.

Enfermedad fúngica invasiva por Purpureocillium lilacinum, a propósito de un caso / Invasive disease due to Purpureocillium lilacinum a case report

Purpureocillium lilacinum, es un moho saprófito, filamentoso, que habita en el suelo y vegetación, los conidios pueden infectar al humano por vía inhalatoria y traumatismo cutáneo. Es un patógeno oportunista causante de infección en inmunocomprometidos. Se han documentado 101 casos en el mundo, uno en Latinoamérica. Se expuso caso de escolar masculino de 8 años, con diagnóstico de leucemia mieloblástica aguda M2, refractaria al tratamiento quimioterápico. Portador de catéter de port, con fiebre intermitente, lesiones algodonosas en paladar blando y duro, úlcera en cara lateral de lengua, ectima en rostro, aumento de volumen en sitio de inserción de catéter, neutropenia profunda y prolongada, trombocitopenia y anemia severa. Inicialmente, cultivos para bacterias y hongos reportaron negativos, pero el paciente poseía factores de riesgo infeccioso. Ante esto se administró antibioticoterapia, con mejoría parcial, con persistencia de la fiebre. Se realizó retrocultivo de catéter de port, hemocultivo periférico, biopsia de lesión de cara y sitio de inserción de catéter, aislándose Purpureocillium lilacinum. Ante esto se indicó voriconazol por 10 días, el cual cumplió sin respuesta. Tras la aplicación de este esquema sin mejoría sostenida, el paciente fallece. Se concluye que el uso de antimicóticos en pacientes inmunodeprimidos y demora en el diagnóstico aumentan los casos de micosis por hongos filamentosos. Se recomienda la toma de hemocultivos y/o biopsias de lesiones sugestivas de micosis. En vista de considerarse una infección oportunista emergente, se planteó presentar este caso inusual por este patógeno, con una revisión bibliográfica para su documentación.

Purpureocillium lilacinum is a saprophytic, filamentous mold that lives in soil and vegetation. The conidia can infect humans through inhalation and skin trauma. It is an opportunistic pathogen that causes infection in immunocompromised patients. 101 cases have been documented in the world, one in Latin America. A case of an 8-year-old male schoolboy was presented, with a diagnosis of M2 acute myeloblastic leukemia, refractory to chemotherapy treatment. Carrier of a port catheter, with intermittent fever, cottony lesions on the soft and hard palate, ulcer on the lateral surface of the tongue, ecthyma on the face, increased volume at the catheter insertion site, deep and prolonged neutropenia, thrombocytopenia and severe anemia. Initially, cultures for bacteria and fungi were negative, but the patient had infectious risk factors. Given this, antibiotic therapy was administered, with partial improvement, with persistence of fever. Retroculture of the port catheter, peripheral blood culture, biopsy of the facial lesion and catheter insertion site were performed, and Purpureocillium lilacinum was isolated. Given this, voriconazole was indicated for 10 days, which he completed without response. After the application of this scheme without sustained improvement, the patient died. It is concluded that the use of antifungals in immunosuppressed patients and delay in diagnosis increase cases of mycosis due to filamentous fungi. Taking blood cultures and/or biopsies of lesions suggestive of mycosis is recommended. In view of it being considered an emerging opportunistic infection, it was proposed to present this unusual case due to this pathogen, with a bibliographic review for its documentation.

Invasive fungal infections in pediatric patients with central nervous system tumors: novel insights for prophylactic treatments?

Background and aims: Invasive fungal disease (IFD) poses significant morbidity and mortality risks, especially in pediatric patients with neoplastic diseases. However, there is a notable lack of data concerning patients with central nervous system (CNS) tumors. Considering vulnerability factors to infections such as neutropenia, corticosteroids, chemotherapy, surgical interventions, and others, this study aims to evaluate the incidence of IFD in pediatric patients with CNS tumors and determine appropriate indications for prophylactic measures. This is a single-center, retrospective study conducted between 2011 and 2022 at the Pediatric Institute of Oncology (IOP-GRAACC-UNIFESP). Results: A total of 38 cases of IFD were diagnosed in 818 children with CNS malignancies (4,6%). The mean age was 3.5 years (0.4-28y), with 22 (57.9%) male patients. Embryonal tumors (18/38, 47.3%) were the most prevalent CNS tumors, followed by low-grade gliomas (13/38, 34.2%). All episodes met the EORTC IFD criteria, and 36/38 (94.7%) were proven. Invasive yeast infections (33/36, 91.6%), predominantly Candida (30/33, 90.9%), were the most common diagnosis. In total, 25 patients (25/38, 65.8%) were receiving chemotherapy, with 13 of them having embryonal tumors. A total of 11 infants were in the Head Start scheme, resulting in a high prevalence of IFD in these group of patients (11/58, 18.9%). In total, 13 (13/38, 34.2%) patients underwent neurosurgery, mostly ventricular-peritoneal shunts revisions (10/13, 76.9%). Nine (9/38, 23.7%) were with prolonged use of corticosteroids, eight of them associated with neurosurgery. Conclusion: Routine systemic antifungal prophylaxis based solely on diagnosis is not recommended for low-risk cases. Evaluating patient- and treatment-specific risk factors is crucial in infants undergoing high-dose chemotherapy with expected neutropenia and in patients requiring prolonged corticosteroid therapy alongside neurosurgical procedures.

"Star of Bethlehem sign" in the analysis of the evolution of brain lesions during and after treatment for neuroparacoccidioidomycosis.

Objective: To describe the clinical and radiological evolution of lesions during and after treatment in patients diagnosed with neuroparacoccidioidomycosis (NPCM). Materials and Methods: This was a retrospective study of the medical records, computed tomography scans, and magnetic resonance imaging (MRI) scans of patients with NPCM treated between September 2013 and January 2022. Results: Of 36 cases of NPCM, eight were included in the study. One patient presented only with pachymeningeal and skull involvement, and seven presented with pseudotumors in the brain. Collectively, the eight patients presented with 52 lesions, of which 46 (88.5%) were supratentorial. There were 32 lesions with a diameter ≤ 1.2 cm, of which 27 (84.4%) disappeared during the treatment. In three cases, there were lesions > 1.2 cm that showed a characteristic pattern of evolution on MRI: an eccentric gadolinium contrast-enhanced nodule, with a subsequent decreased in the size and degree of contrast enhancement of the lesions. Conclusion: In NPCM, supratentorial lesions seem to predominate. Lesions ≤ 1.2 cm tend to disappear completely during treatment. Lesions > 1.2 cm tend to present with a similar pattern, designated the "Star of Bethlehem sign", throughout treatment.

Objetivo: Descrever a evolução clínica e radiológica das lesões durante e após o tratamento de pacientes diagnosticados com neuroparacoccidioidomicose (NPCM). Materiais e Métodos: Revisamos os prontuários médicos, estudos de tomografia computadorizada e ressonância magnética (RM) de pacientes com NPCM de nossa instituição, no período de setembro de 2013 a janeiro de 2022. Resultados: Dos 36 casos de NPCM, oito foram incluídos no presente estudo. Um caso apresentava apenas envolvimento paquimeníngeo e ósseo craniano e sete casos apresentavam lesões encefálicas pseudotumorais, totalizando 52 lesões, sendo 46 (88,5%) supratentoriais. Dentre 32 lesões com diâmetro ≤ 1,2 cm, 27 (84,4%) apresentaram resolução completa durante o tratamento. Três casos apresentaram padrão semelhante de evolução da lesão na RM em lesões > 1,2 cm, caracterizado pelo aparecimento de nódulo excêntrico com impregnação pelo gadolínio, seguido de redução das dimensões e do realce nodular pelo contraste nos estudos subsequentes. Conclusão: A NPCM apresenta-se predominantemente com lesões supratentoriais. Lesões ≤ 1,2 cm tendem a desaparecer completamente durante o tratamento. Lesões > 1,2 cm tendem a apresentar um padrão de imagem de RM característico ao longo do tratamento, descrito como o "sinal da Estrela de Belém".

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.

Rare Yeasts in Latin America: Uncommon Yet Meaningful.

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.

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.

Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico.

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.

Pediatric invasive fungal rhinosinusitis.

Pediatric invasive fungal rhinosinusitis (PIFR) is a rapidly progressive, potentially fatal disease. Previous medical literature demonstrates that its early diagnosis significantly reduces the risk of mortality in these patients. This study aims to present an updated clinical algorithm for optimized diagnosis and management of PIFR. A comprehensive review was conducted with only original, full-text articles published in English and Spanish from Cochrane Library, Pub-Med/MEDLINE, Embase, Scopus, and Google Scholar between January 2010 and June 2022. Relevant information was extracted and then integrated to develop a clinical algorithm for a proper diagnosis and management of PIFR.

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

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.

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 infections in pediatric patients with acute myeloid leukemia in a tertiary hospital.

Introduction: Acute leukemia accounts for more than 30% of all pediatric cancer cases, and of these, 15-20% are acute myeloid leukemia (AML). Children who super from AML are more likely to develop infections due to the humoral and cellular immune deficits generated by the disease and its treatment. The incidence of fungal infections is underestimated; reports show that up to 75% of fungal infections go undiagnosed until autopsy. In only 30 years, the incidence of invasive candidiasis has increased by 40-fold. Thus, the high morbidity and mortality associated with fungal infections in hematological patients make it necessary to adopt preventive measures. Methods: This work aimed to retrospectively identify pediatric patients with acute myeloid leukemia and invasive fungal diseases (IFDs) in a Latin American tertiary care hospital. A retrospective analysis of 36 clinical records of pediatric patients diagnosed with AML from 2007 to 2017 was carried out. Results: One hundred and twenty-nine hospitalizations were associated with infectious events. Thirteen patients in our study presented 15 infectious events associated with IFDs (11.6%). Two patients died because of complications related to IFDs (15.3%). The most frequent IFD type was aspergillosis, which was observed in 7 cases, followed by Candidemia, which was observed in 4 cases. The most frequent clinical manifestations were fever and respiratory distress. Discussion: Mortality due to IFD can be prevented with effective pharmacotherapy. An appropriate antifungal prophylaxis strategy still needs to be developed through larger prospective studies in Latin America.

Rhino-orbital mucormycosis in a Mexican patient with COVID-19: Case report.

BACKGROUND: A variety of bacterial and fungal co-infections may be attributed to the coronavirus disease 2019 (COVID-19), particularly in people who already have a medical condition such diabetes mellitus or those who received large dosages of steroids. CASE REPORT: We described a 52-year-old diabetic man who was receiving high doses of dexamethasone and antibiotics while receiving ambulatory care for COVID-19 pneumonia. His anterior rhinoscopy revealed a necrotic scab, and a sample confirmed Mucor spp. He underwent surgery and was given amphotericin as a result of the severity of the condition, palpebral ptosis, and right ocular palsy he was experiencing. The patien ́s progression was satisfactory. CONCLUSIONS: pre-existing diabetes mellitus, previous steroid and antimicrobial use, as well as SARS-CoV-2 infection are some of the risk factors associated with Mucor spp. infection. Prompt detection of mucormycosis is important in the management of these affected patients.

ANTECEDENTES: A la enfermedad por coronavirus (COVID-19) se le han atribuido diversas coinfecciones bacterianas y fúngicas, especialmente en sujetos con enfermedades preexistentes (diabetes mellitus) o en quienes han recibido altas dosis de corticosteroides. REPORTE DE CASO: Paciente masculino de 52 años, con antecedente de diabetes mellitus, quien recibió altas dosis de dexametasona y antibióticos mientras recibía atención ambulatoria por neumonía secundaria a COVID-19. La rinoscopia anterior reveló una costra necrótica, y una muestra de exudado confirmó la coexistencia de Mucor spp. Debido a la complicación del cuadro clínico, ptosis palpebral y parálisis ocular derecha, se le administró anfotericina B y fue intervenido quirúrgicamente. La evolución del paciente fue satisfactoria. CONCLUSIONES: La diabetes mellitus preexistente, el consumo de corticosteroides y antimicrobianos, además de la infección por SARS-CoV-2 son factores de riesgo asociados con la infección por Mucor spp. Es importante la detección oportuna de mucormicosis en el tratamiento de estos pacientes.