Necrotizing pneumonia due to Aspergillus and Salmonella after immune checkpoint inhibitor treatment: An unusual case and review of the literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising new treatment for different types of cancer. The infectious complications in patients taking ICIs are rare. CASE REPORT: A 58-year-old male who received chemotherapy consisting of pembrolizumab (PD-1 inhibitor) for esophagus squamous cell carcinoma one month before was admitted to the emergency room with shortness of breath soon after fiberoptic bronchoscopy, which was done for the inspection of the lower airway. A computed tomography of the chest revealed a progressive consolidation on the right upper lobe. Salmonella group D was isolated from the bronchoalveolar lavage (BAL) fluid culture. The fungal culture of the same clinical sample yielded Aspergillus niger; furthermore, a high titer (above the cut-off values) of Aspergillus antigen was found both in the BAL fluid and serum of the patient. Despite the effective spectrum and appropriate dose of antimicrobial treatment, the patient died due to disseminated intravascular coagulopathy. CONCLUSIONS: Awareness of unusual pathogens in the etiology of pneumonia after ICI treatment may help to avoid underdiagnosis.

Necrotizing pneumonia due to Aspergillus and Salmonella after immune checkpoint inhibitor treatment: An unusual case and review of the literature / Neumonía necrotizante por Aspergillus y Salmonella tras tratamiento con un inhibidor de puntos de control inmunitario: un caso inusual y revisión de la literatura

Background: Immune checkpoint inhibitors (ICIs) are a promising new treatment for different types of cancer. The infectious complications in patients taking ICIs are rare. Case report: A 58-year-old male who received chemotherapy consisting of pembrolizumab (PD-1 inhibitor) for esophagus squamous cell carcinoma one month before was admitted to the emergency room with shortness of breath soon after fiberoptic bronchoscopy, which was done for the inspection of the lower airway. A computed tomography of the chest revealed a progressive consolidation on the right upper lobe. Salmonella group D was isolated from the bronchoalveolar lavage (BAL) fluid culture. The fungal culture of the same clinical sample yielded Aspergillus niger; furthermore, a high titer (above the cut-off values) of Aspergillus antigen was found both in the BAL fluid and serum of the patient. Despite the effective spectrum and appropriate dose of antimicrobial treatment, the patient died due to disseminated intravascular coagulopathy. Conclusions: Awareness of unusual pathogens in the etiology of pneumonia after ICI treatment may help to avoid underdiagnosis.(AU)

Antecedentes: Los fármacos inhibidores de puntos de control inmunitario (ICI) son una nueva y prometedora opción de tratamiento para diferentes tipos de cáncer. Las complicaciones infecciosas en pacientes que toman ICI son poco frecuentes. Caso clínico: Un varón de 58 años que recibió quimioterapia con pembrolizumab (inhibidor de PD-1) para un carcinoma de células escamosas de esófago hacía un año, ingresó en Urgencias por dificultad respiratoria poco después de realizarse una broncoscopia de fibra óptica para una inspección de las vías aéreas inferiores. La tomografía computarizada de tórax reveló una consolidación progresiva en el lóbulo superior derecho. Se aisló Salmonella grupo D en el cultivo del líquido de lavado broncoalveolar (LBA). En el cultivo de hongos de la misma muestra creció Aspergillus niger; además, se detectó antígeno (por encima de los valores de corte) de Aspergillus tanto en la muestra del LBA como en el suero del paciente. A pesar del espectro eficaz y la dosis adecuada del antifúngico utilizado, el paciente falleció debido a una coagulopatía intravascular diseminada. Conclusiones: El conocimiento de patógenos inusuales en la etiología de la neumonía tras el tratamiento con ICI puede ayudar a evitar el infradiagnóstico.(AU)

Evaluation of the diagnostic accuracy of galactomannan from the bronchoalveolar lavage fluid of patients with suspected invasive pulmonary aspergillosis.

BACKGROUND: Several studies to evaluate the accuracy of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) as a diagnostic tool have been carried out; however, there are still controversies about the optimal cut-off point of BALF GM. AIMS: The objective of this study was to determine the diagnostic accuracy and the optimal cut-off point on BALF GM from patients with suspected invasive pulmonary aspergillosis (IPA) in a tertiary care hospital. METHODS: A cross-sectional study with 188 patients (≥18 years) that had undergone a bronchoscopy with BAL due to suspected IPA was carried out. IPA was diagnosed according to the EORTC/MSG guidelines. RESULTS: The optimal optical density cut-off point for BALF GM was 0.67, with sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 70%, 32.3%, and 100%, respectively. CONCLUSIONS: BALF GM detection proved to be a useful supplementary technique in the early diagnosis of IPA in both neutropenic and non-neutropenic patients.

Evaluation of the diagnostic accuracy of galactomannan from the bronchoalveolar lavage fluid of patients with suspected invasive pulmonary aspergillosis

Background:Several studies to evaluate the accuracy of galactomannan (GM) in bronchoalveolar lavage fluid (BALF) as a diagnostic tool have been carried out; however, there are still controversies about the optimal cut-off point of BALF GM.Aims:The objective of this study was to determine the diagnostic accuracy and the optimal cut-off point on BALF GM from patients with suspected invasive pulmonary aspergillosis (IPA) in a tertiary care hospital.Methods:A cross-sectional study with 188 patients (≥18 years) that had undergone a bronchoscopy with BAL due to suspected IPA was carried out. IPA was diagnosed according to the EORTC/MSG guidelines.Results:The optimal optical density cut-off point for BALF GM was 0.67, with sensitivity, specificity, positive predictive value, and negative predictive value of 100%, 70%, 32.3%, and 100%, respectively.Conclusions:BALF GM detection proved to be a useful supplementary technique in the early diagnosis of IPA in both neutropenic and non-neutropenic patients. (AU)

Antecedentes:Diversos estudios han evaluado la precisión del galactomanano (GM) como herramienta diagnóstica en el líquido de lavado broncoalveolar (LBA); sin embargo, todavía existen controversias sobre el punto de corte óptimo de LBA GM.Objetivos:El objetivo de este estudio fue determinar la precisión diagnóstica y el punto de corte óptimo en LBA GM de pacientes con sospecha de aspergilosis pulmonar invasora (API) en un hospital de tercer nivel.Métodos:Se realizó un estudio transversal en el que fueron incluidos 188 pacientes (≥18años) a los que se les había realizado una broncoscopia con LBA por sospecha de API. La API se diagnosticó de acuerdo con las guías EORTC/MSG.Resultados:El punto de corte óptimo para el valor densidad óptica de LBA GM fue de 0,67, con sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo del 100%, 70%, 32,3% y 100%, respectivamente. (AU)ConclusionesLa detección de GM en LBA demostró ser un procedimiento útil en el diagnóstico precoz de la API, tanto en pacientes neutropénicos como en no neutropénicos.

Invasive pulmonary aspergillosis in patients with acute respiratory syndrome by COVID-19.

Patients with COVID-19 who are admitted to intensive care unit (ICU) are at high risk of developing secondary infections, including invasive fungal infections such as invasive pulmonary aspergillosis (IPA). The main purpose was to analyse the putative COVID-19 Associated Pulmonary Aspergillosis (CAPA) patients in our setting. In these patients, we performed mycological culture in bronchoalveolar lavage (BAL) for isolation of Aspergillus sp. We followed the AspICU algorithm to diagnose putative IPA. Moreover, we considered relevant the positivity of Galactomannan in BAL. We diagnosed putative IPA in 3 patients. The common features of these 3 patients were: more than 21 days of stay in ICU, severe acute respiratory distress syndrome (ARDS) and treatment with steroids (1 mg/kg per day). Therefore, CAPA has to be systematically considered although a new algorithm to diagnose it is needed to treat patients in early stages in order to avoid catastrophic outcomes.

Aspergilosis pulmonar invasiva en pacientes con síndrome de distrés respiratorio por COVID-19 / Invasive pulmonary aspergillosis in patients with acute respiratory syndrome by COVID-19

Los pacientes con COVID-19 que ingresan en una unidad de cuidados intensivos (UCI), tienen un alto riesgo de desarrollar infecciones secundarias, incluyendo infecciones fúngicas invasivas como aspergilosis pulmonar invasiva (API). El objetivo principal fue el análisis de los casos con sospecha de COVID-19 Associated Pulmonary Aspergillosis (CAPA) en nuestra unidad. En estos pacientes realizamos cultivo micológico en el lavado broncoalveolar como métodos de aislamiento de Aspergillus sp. Se siguió el algoritmo AspICU para establecer el diagnóstico de API probable. Además, considerando también relevante la positividad del antígeno de galactomanano. Se confirmó API probable en 3 de ellos. Los 3 pacientes permanecieron ingresados más de 21 días por SDRA grave, y recibieron corticoterapia (1mg/kg/día). Por tanto, la CAPA se debe considerar de forma sistemática, aunque se necesita un nuevo algoritmo diagnóstico que permita tratamiento precoz por las consecuencias deletéreas que puede implicar en los pacientes críticos.(AU)

Patients with COVID-19 who are admitted to intensive care unit (ICU) are at high risk of developing secondary infections, including invasive fungal infections such as invasive pulmonary aspergillosis (IPA). The main purpose was to analyse the putative COVID-19 Associated Pulmonary Aspergillosis (CAPA) patients in our setting. In these patients, we performed mycological culture in bronchoalveolar lavage (BAL) for isolation of Aspergillus sp. We followed the AspICU algorithm to diagnose putative IPA. Moreover, we considered relevant the positivity of galactomannan in BAL. We diagnosed putative IPA in 3 patients. The common features of these 3 patients were: more than 21 days of stay in ICU, severe acute respiratory distress syndrome (ARDS) and treatment with steroids (1mg/kg per day). Therefore, CAPA has to be systematically considered although a new algorithm to diagnose it is needed to treat patients in early stages in order to avoid catastrophic outcomes.(AU)

Neumonía por coinfección de Aspergillus fumigatus y Pneumocystis jirovecii en un paciente no VIH: Reporte de caso / Pneumonia due to Aspergillus fumigatus and Pneumocystis jirovecii coinfection in a non-HIV- infected patient: Case report

RESUMEN La aspergilosis pulmonar invasiva es una enfermedad presente principalmente en pacientes inmunocomprometidos con alta carga de mortalidad. La neumonía por Pneumocystis jirovecii es una infección oportunista potencialmente mortal que afecta a pacientes inmunocomprometidos por diversas etiologías. La coinfección por estos patógenos en pacientes inmunocompetentes es inusual. Reportamos un caso de un paciente sin las causas tradicionales de inmunocompromiso en el desarrollo de una neumonía en coinfección por Aspergillus fumigatus y Pneumocystis jirovecii.

ABSTRACT Invasive pulmonary aspergillosis is a condition that mainly occurs in immunosuppressed patients, and it has a high mortality rate. Pneumonia caused by Pneumocystis jirovecii is a potentially lethal opportunistic infection affecting immunosuppressed patients with different etiology. Coinfection by Aspergillus and P. jirovecii in immunocompetent patients is unusual. We report a case of a patient with no common causes of immunosuppression who developed pneumonia coinfection caused by Aspergillus fumigatus and Pneumocystis jirovecii.

Invasive pulmonary aspergillosis in patients with acute respiratory syndrome by COVID-19. / Aspergilosis pulmonar invasiva en pacientes con síndrome de distrés respiratorio por COVID-19.

Patients with COVID-19 who are admitted to intensive care unit (ICU) are at high risk of developing secondary infections, including invasive fungal infections such as invasive pulmonary aspergillosis (IPA). The main purpose was to analyse the putative COVID-19 Associated Pulmonary Aspergillosis (CAPA) patients in our setting. In these patients, we performed mycological culture in bronchoalveolar lavage (BAL) for isolation of Aspergillus sp. We followed the AspICU algorithm to diagnose putative IPA. Moreover, we considered relevant the positivity of galactomannan in BAL. We diagnosed putative IPA in 3 patients. The common features of these 3 patients were: more than 21 days of stay in ICU, severe acute respiratory distress syndrome (ARDS) and treatment with steroids (1mg/kg per day). Therefore, CAPA has to be systematically considered although a new algorithm to diagnose it is needed to treat patients in early stages in order to avoid catastrophic outcomes.

[Individualized antifungal therapy in critically ill patients with invasive fungal infection]. / Tratamiento antifúngico individualizado en el paciente crítico con infección fúngica invasora.

Invasive candidiasis (IC) is the most common invasive fungal infection (IFI) affecting critically ill patients, followed by invasive pulmonary aspergillosis (IPA). International guidelines provide different recommendations for a first-line antifungal therapy and, in most of them, echinocandins are considered the first-line treatment for IC, and triazoles are so for the treatment of IPA. However, liposomal amphotericinB (L-AmB) is still considered a second-line therapy for both clinical entities. Although in the last decade the management of IFI has improved, several controversies persist. The antifungal drugs currently available may have a suboptimal activity, or be wrongly used in certain IFI involving critically ill patients. The aim of this review is to analyze when to provide individualized antifungal therapy to critically ill patients suffering from IFI, emphasizing the role of L-AmB. Drug-drug interactions, the clinical status, infectious foci (peritoneal candidiasis is discussed), the fungal species involved, and the need of monitoring the concentration of the antifungal drug in the patient are considered.

Necrosis pulmonar masiva por micosis / Massive pulmonary necrosis due to mycosis

Introducción: La aspergilosis es una infección micótica oportunista que se presenta fundamentalmente en pacientes inmunodeprimidos y su principal fuente de transmisión lo constituyen las esporas presentes en el aire de salones de operaciones y unidades de cuidados intensivos. Objetivo: Presentar un caso de una micosis pulmonar masiva por una variante angioinvasiva de Aspergillus. Caso clínico: Se presenta un paciente con aspergilosis pulmonar grave, diagnosticada después de la resección de un tumor mediastinal. Se describen las características de la primera intervención, la evolución postoperatoria que condujo a la segunda, se muestran las imágenes tomográficas, quirúrgicas, microbiológicas y anátomo-patológicas que permitieron definir el diagnóstico. Conclusiones: La posibilidad de una micosis pulmonar debe tenerse en cuenta, aun cuando sea una afección rara y de manejo difícil, en pacientes inmunodeprimidos, con condensación pulmonar rebelde al tratamiento(AU)

Introduction: Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units. Objective: To present a case of a massive pulmonary mycosis due to an angioinvasive variant of Aspergillus. Clinical case: A patient with severe pulmonary aspergillosis, diagnosed after resection of a mediastinal tumor, is presented. The characteristics of the first intervention are described, the postoperative evolution that led to the second one, the tomographic, surgical, microbiological and anatomo-pathological images that allowed to define the diagnosis are shown. Conclusions: The possibility of a pulmonary mycosis should be taken into account, even when it is a rare and difficult-to-handle condition, in immunocompromised patients, with pulmonary condensation that is rebellious to treatment. Aspergillosis is an opportunistic fungal infection that occurs mainly in immunosuppressed patients and its main source of transmission is the spores present in the air of operating rooms and intensive care units(AU)

Clinical factors associated with pulmonary aspergillosis in patients with chronic obstructive pulmonary disease. / Factores clínicos asociados a enfermedad pulmonar por Aspergillus spp. en pacientes con enfermedad pulmonar obstructiva crónica.

OBJECTIVE: To explore the clinical and epidemiological characteristics of chronic obstructive pulmonary disease (COPD) patients with Aspergillus spp. isolation from respiratory samples, and to identify which factors may help us to distinguish between colonisation and infection. METHODS: A retrospective cohort study was performed. All patients with COPD and respiratory isolation of Aspergillus spp. over a 12-year period were included. Patients were assigned to 2 categories: colonisation and pulmonary aspergillosis (PA), which includes the different clinical forms of aspergillosis. A binary logistic regression model was performed to identify the predictive factors of PA. RESULTS: A total of 123 patients were included in the study: 48 (39.0%) with colonisation and 75 (61.0%) with PA: 68 with probable invasive pulmonary aspergillosis and 7 with chronic pulmonary aspergillosis. Spirometric stages of the GOLD classification were not correlated with a higher risk of PA. Four independent predictive factors of PA in COPD patients were identified: home oxygen therapy (OR: 4.39; 95% CI: 1.60-12.01; P=.004), bronchiectasis (OR: 3.61; 95% CI: 1.40-9.30; P=.008), hospital admission in the previous three months (OR: 3.12; 95% CI: 1.24-7.87; P=.016) and antifungal therapy against Candida spp. in the previous month (OR: 3.18; 95% CI: 1.16-8.73; P=.024). CONCLUSIONS: Continuous home oxygen therapy, bronchiectasis, hospital admission in the previous three months and administration of antifungal medication against Candida spp. in the previous month were associated with a higher risk of pulmonary aspergillosis in patients with COPD.

Identificación molecular de Aspergillus fumigatus aislados de pacientes con aspergilosis invasiva / Molecular identification of Aspergillus fumigatus isolated from patients with invasive aspergillosis

RESUMEN El objetivo del estudio fue identificar molecularmente cepas de aspergillus aislados de pacientes con aspergilosis invasiva (AI), que fueron tipificadas primariamente como Aspergillus fumigatus sensu lato por métodos fenotípicos convencionales. Se trabajó con 20 cepas de la micoteca de la sección de micología del Instituto de Medicina Tropical "Daniel A. Carrión". Para obtener el ADN fúngico se emplearon las técnicas de choque térmico, tratamiento enzimático y columnas de silica-gel; y se almacenó a -20 0C para conservarlo. En el procedimiento de la reacción en cadena de la polimerasa en tiempo real (qPCR) se incluyeron primers marcados con fluorocromo, los cuales amplificaron las secuencias específicas de A. fumigatus. La fluorescencia se midió con el termociclador al final de la fase de hibridación de cada ciclo. Se identificó molecularmente que sólo el 50% de las cepas estudiadas pertenecen a la especie Aspergillus fumigatus sensu stricto.

ABSTRACT The objective of the study was to identify molecularly-isolated strains of Aspergillus from patients with invasive aspergillosis (IA); these strains were primarily typed as Aspergillus fumigatus sensu lato by conventional phenotypic methods. We worked with 20 strains from the mycology section of the Institute of Tropical Medicine "Daniel A. Carrión." To obtain the fungal DNA, thermal shock, enzymatic treatment, and silica gel column techniques were used; and it was stored at -20°C to preserve it. The real-time polymerase chain reaction (qPCR) procedure included fluorochrome-labeled primers, which amplified the specific sequences of A. fumigatus. Fluorescence was measured with the thermocycler at the end of the hybridization phase of each cycle. It was molecularly-identified that only 50% of the strains studied belong to the species Aspergillus fumigatus sensu stricto.

Aspergilosis pulmonar invasiva: reporte de un caso / Invasive pulmonary aspergillosis: A case report

El hongo Aspergillus spp. causa infecciones oportunistas en huéspedes inmunocomprometidos. Cursa con una variedad de síndromes clínicos en el pulmón, que incluyen aspergilosis invasiva, aspergilosis pulmonar necrótica crónica, aspergilosis broncopulmonar alérgica y aspergiloma, cuya manifestación depende del tipo de relación con el huésped. El aspergiloma resulta de lesiones colonizadas por Aspergillus spp. en el árbol bronquial, en tanto que las formas invasivas se caracterizan por la presencia de hifas por debajo de la membrana basal del árbol bronquial. El objetivo de este trabajo es describir el caso de una paciente con aspergilosis pulmonar invasiva en su forma de traqueobronquitis seudomembranosa, considerando el curso clínico, el diagnóstico y el manejo paraclínico. Se trató de una paciente de cinco años de edad con antecedentes de anemia de Fanconi, que fue llevada a consulta con neutropenia febril y neumonía. Se inició el tratamiento antibiótico con cefepime, sin mejoría clínica. La tomografía computadorizada (TC) de tórax reveló opacidades parenquimatosas en ambas bases pulmonares. En una fibrobroncoscopia se encontró una lesión exofítica blanquecina en el bronquio principal derecho, que se sometió a biopsia, y se practicó un lavado broncoalveolar. En el examen de histopatología se hallaron hifas tabicadas a 45°, y el resultado del cultivo reveló la presencia del complejo Aspergillus flavi, por lo que se inició la administración de voriconazol. Se revisaron los reportes en la literatura científica sobre la infección pulmonar por Aspergillus spp. en niños, con énfasis en los síndromes clínicos, y en su manejo y tratamiento. Ante la presencia de síntomas respiratorios en pacientes pediátricos con enfermedades hematológicas que cursen con neutropenia febril, es indispensable considerar como agentes etiológicos los hongos, entre los cuales Aspergillus spp. se presenta frecuentemente causando diferentes síndromes clínicos.

The fungus Aspergillus spp. causes infections in immunocompromised hosts and produces a variety of clinical syndromes including lung tracheobronchial, chronic necrotizing pulmonary and allergic bronchopulmonary manifestations, as well as aspergilloma, depending on the type of host-fungus relationship involved. Aspergilloma is usually colonized by Aspergillus spp. lesions in the bronchial tree, while invasive forms are characterized by the presence of hyphae below its basement membrane. The objective of the present study was to describe the case of a pediatric patient with invasive pulmonary aspergillosis in the form of pseudomembranous tracheobronchitis, including the clinical course, diagnostic approach and paraclinical care provided. The patient was a 5-year-old female with a history of Fanconi anemia who presented with febrile neutropenia and pneumonia. Antibiotic treatment with cefepime provided no improvement in the patient´s condition and computed tomography of the thorax revealed bibasilar pulmonary opacities. Bronchoalveolar lavage and a lesion biopsy were performed after diagnostic bronchoscopy showed a white exophytic lesion. Since pathologic examination revealed numerous septate fungal hyphae exhibiting 45° branching compatible with Aspergillus spp., the patient was treated with voriconazole. Bronchoalveolar lavage culture produced fungi of the Aspergillus flavi complex. A review of pulmonary Aspergillus spp. infection in children is also included, with emphasis on the management and treatment of clinical syndromes. In pediatric patients with hematological diseases who present with febrile neutropenia and respiratory symptoms, it is essential to consider fungi as potential etiologic agents including Aspergillus spp., which is common and causes a variety of clinical syndromes.

Aspergilosis pulmonar invasiva en paciente neutropenico / Invasive pulmonary aspergillosis in neutropenic patient

La aspergilosis pulmonar invasiva (API) es una infección micótica oportunista necrotizante en pacientes inmunocomprometidos. El germen causante de la enfermedad tiene tropismo vascular que ocasiona trombosis y necrosis isquémica con la formación de cavidades, y según el grado de deterioro inmunitario se asocia a una mortalidad elevada. La clásica triada en pacientes neutropénicos comprende: la fiebre, el dolor pleurítico y la hemoptisis. La radiografía de tórax puede ser normal en la aspergilosis pulmonar invasiva o mostrar algunos signos radiológicos característicos como la consolidación, nódulos, y el signo de halo o el signo del aire creciente, en la tomografía computarizada. Lo más frecuente es la consolidación pulmonar que se presenta en alrededor del 60% de los pacientes. La mortalidad por API excede el 50% en pacientes neutropénicos, y es mayor a 90% en los casos de trasplante de médula ósea. El medicamento de elección es el voriconazol, otras alternativas es la anfotericina B. Los resultados del tratamiento no son siempre satisfactorios debido a la tardanza en la iniciación de la terapia farmacológica y la limitación en el número de agentes antimicóticos activos disponibles. Se presenta el caso de un paciente de sexo masculino de 61 años, con diagnóstico de API por la importancia que merece en la identificación temprana de esta patología, diagnóstico y tratamiento oportunos, evitando complicaciones que lleven a una mortalidad elevada

Invasive pulmonary aspergillosis (IPA) is an necrotizing opportunistic fungal infection in immunocompromised patients necrotizing. The germ causing the disease has vascular tropism that causing thrombosis and ischemic necrosis with the formation of cavities, and the degree of immune impairment is associated with high mortality. The classic triad in neutropenic patients include: fever, pleuritic pain and hemoptysis. The chest radiograph may be normal in the IPA or showing some characteristic radiological signs such as consolidation, nodules, and the sign of halo or air crescent sign, on computed tomography. The most frequent presentation is pulmonary consolidation having about 60% of patients. API mortality exceeds 50% in neutropenic patients, and more than 90% in cases of bone marrow transplantation. The drug of choice is voriconazole, amphotericin B in other alternatives. Treatment results are not always satisfactory because of the delay in the initiation of drug therapy and the limitation on the number of active antifungal agents available. Its reports the case of a male patient of 61 years, diagnosed with API for the importance it deserves in the early identification of this pathology, diagnosis and treatment, avoiding complications with high mortality.

Updates on Aspergillus, Pneumocystis and other opportunistic pulmonary mycoses.

Mycoses are serious diseases with potentially fatal outcome. The introduction of immunosuppressive treatments and life support techniques has led to a growing prevalence of different degrees of immunosuppression. Compromised immune response is the primary risk factor for the development of opportunistic mycoses. Early diagnosis and treatment are crucial for improving prognosis. However, isolation in cultures or identification using antigen detection techniques cannot distinguish between colonization and invasive infection, and the clinical status of the patient often prevents biopsy sampling. Clinicians thus find themselves in an uncertain position, requiring them to quickly recognize clinical and radiological signs and interpret microbiological results in context. The aim of this review is to provide a general overview of the profile of patients susceptible to these infections, the role of the immune system and, in more detail, the major diagnostic developments that have gained most acceptance and recognition among the scientific community.

[Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease]. / Aspergilosis pulmonar invasiva en el enfermo con enfermedad pulmonar obstructiva crónica.

Invasive pulmonary aspergillosis (IPA) is a common infection in immunocompromised patients with hematological malignancies or allogenic stem cell transplantation, and is less frequent in the context of chronic obstructive pulmonary disease (COPD). Mucociliary activity impairment, immunosuppression due to the inhibition of alveolar macrophages and neutrophils by steroids, and receiving broad-spectrum antibiotics, play a role in the development of IPA in COPD patients. Colonized patients or those with IPA are older, with severe CODP stage (GOLD≥III), and have a higher number of comorbidities. The mortality rate is high due to the fact that having a definitive diagnosis of IPA in COPD patients is often difficult. The main clinical and radiological signs of IPA in these types of patients are non-specific, and tissue samples for definitive diagnosis are often difficult to obtain. The poor prognosis of IPA in COPD patients could perhaps be improved by faster diagnosis and prompt initiation of antifungal treatment. Some tools, such as scales and algorithms based on risk factors of IPA, may be useful for its early diagnosis in these patients.

[The different manifestations of pulmonary aspergillosis: multidetector computed tomography findings]. / Las diferentes manifestaciones de la aspergilosis pulmonar. Hallazgos en tomografía computarizada multidetector.

Pulmonary aspergillosis is a fungal infection usually caused by inhaling Aspergillus fumigatus spores. However, when we talk about aspergillosis, we normally refer to the spectrum of clinical and radiological findings that depend directly on the patient's immune status, on the prior existence of lung disease, and on the virulence of the infective organism. There are four types of pulmonary aspergillosis (aspergilloma, allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, and invasive aspergillosis), and each type has its own distinct radiologic findings. We review the signs of pulmonary aspergillosis on multidetector computed tomography and we correlate them with patients' symptoms and immune responses. Likewise, we discuss the differential diagnoses.

Aspergilosis diseminada: hallazgos postmortem en un caso de sepsis materna. ¿Es el embarazo un estado de inmunosupresión? / Disseminated aspergillosis: postmortem findings in a case of maternal sepsis

Se comunica un caso de muerte materno-fetal con diagnóstico de aspergilosis diseminada concluido a través del estudio de autopsia. Caso: Mujer de 20 años de edad con antecedente de preeclampsia quien en su segundo embarazo inició con dolor obstétrico asociado a fiebre y ataque al estado general. El trabajo de parto concluyó con la expulsión de un feto óbito macerado y placenta fétida, hipotonía uterina e inestabilidad hemodinámica. Fue referida a segundo nivel, cursaba con fiebre persistente, foco séptico pélvico, trastornos de la ventilación, evidencia de lesiones encefálicas por tomografía, sangrado de tubo digestivo, oliguria, datos de respuesta inflamatoria sistémica y necrosis bilateral de miembros inferiores. Falleció a los 10 días de haber sido internada. Resultados: En el examen necrológico, la División de Anatomía Patológica halló pulmones con áreas extensas de consolidación y hemorragia, corazón con vegetaciones valvulares y murales, así como cerebro con múltiples lesiones similares a infarto. La microscopía de luz reveló la presencia de hifas septadas ramificadas en ángulos de 45° que transgredían el lumen de arterias en pulmón, asentadas sobre la superficie endocárdica e invadían el miocardio, el espacio subaracnoideo y neurópilo. Dichas hifas también se identificaron en los cortes histológicos de tiroides, tráquea, estómago y riñón. Conclusión: La aspergilosis diseminada es una entidad de elevada letalidad que usualmente afecta a pacientes inmunocomprometidos, específicamente a quienes cursan con neutropenia. Si bien durante el embarazo el sistema inmune experimenta determinadas adaptaciones fisiológicas, éstas no predisponen per se al desarrollo de infecciones oportunistas.

We describe autopsy findings in a case of maternal death caused by invasive aspergillosis in its disseminated form. Case: 20 year old female with previous medical history of preeclampsia who started with malaise, pelvic pain and fever during her second pregnancy. A fetal obitus was obtained after labor although she remained with uterine hypotony and hemodynamic unsteadiness. She was referred to a general hospital subsisting with fever, acute pelvic sepsis, deteriorated ventilatory function, cerebral lesions visualized by tomography, gastrointestinal bleeding, oliguria and systemic inflammatory response with bilateral acral lower extremities necrosis. She died ten days after her arrival and autopsy was authorized. Results: Necropsy uncovered lungs with consolidated areas and extensive haemorrhage, valvular and mural heart vegetations and numerous cerebral lesions with infarct-like appeareance. Light microscopy revealed the presence of septate hyphae with regular acute angle branching invading lung microvasculature, endocardial surface, myocardium, Virchow-Robin space and neuropil. The hyphae were also identified in thyroid, trachea, gastric mucosa and kidney histological sections. Conclusion: Disseminated aspergillosis is a high-mortality infectious process that usually affects immunocompromised patients, specially those coursing with neutropenia. Despite immunological changes experienced as part of normal pregnancy, these per se do not predispose the mother to infections caused by opportunistic pathogens.

Caracterización de los pacientes con sospecha de aspergilosis invasiva estudiados con prueba Platelia Aspergillus® / Characterization of patients with suspected invasive aspergillosis studied by Platelia test

Objetivo: describir las características de los pacientes en los que se realizó prueba Platelia Aspergillus® por sospecha de AI, y los resultados de la prueba según las categorías diagnósticas. Metodología: se revisaron retrospectivamente las historias clínicas de pacientes con sospecha de AI atendidos en instituciones de salud de Medellín a quienes se les realizó la prueba Platelia Aspergillus®. Se colectaron y analizaron de manera descriptiva los datos clínicos, imaginológicos, microbiológicos y los resultados de la prueba Platelia Aspergillus®. Resultados: se incluyeron 78 pacientes atendidos entre 2006- 2008. Se diagnosticó AI en 21 (26.9%) pacientes, colonización en ocho (10.3%) pacientes. La forma pulmonar invasiva aguda se encontró en 17 (81.0%), forma diseminada en tres (14.3%). La fiebre y la disnea fueron la principal manifestación. En la tomografía de pulmón se observaron más frecuentemente nódulos pulmonares. La prueba fue positiva en 31 (39.7%) pacientes, en 50% de los pacientes colonizados. En 17 (47.2%) de los 36 pacientes recibieron antibióticos betalactámicos, la prueba fue positivo. Conclusiones: la AI puede encontrarse hasta en la tercera parte de pacientes con sospecha clínica; sin embargo, el diagnóstico es difícil debido al cuadro clínico inespecífico, además de las dificultades para obtener muestras clínicas y al pobre rendimientode las pruebas diagnósticas.

Objective: to describe the characteristics of patients with suspected IA, who were studied with the platelia test as well as theresults according to different diagnostic categories. Methods: the medical records of patients with suspected IA treated at health facilities in Medellin who were tested with platelia were retrospectively reviewed. Clinical data, imaging, microbiology and the platelia test results were collected and descriptively analyzed. Results: we included 78 patients treated from 2006 to 2008. IA was diagnosed in 21 (26.9%) patients and colonization was found in 8 (10.3%) patients. The acute invasive pulmonary form was found in 17 (81.0%), disseminated form in three (14.3%). Fever and dyspnea were the principal manifestation. Nodules were found more frequently in lung tomography. The tests were positive in 31 (39.7%) patients and in 50% of colonized patients. In 17 (47.2%) of 36 patients who received beta-lactamantibiotics, the test showed a positive result. Conclusions: IA can be found in up to one third of patients with clinical suspicion, but diagnosis remains difficult because of the nonspecific clinical picture, coupled with the difficulty for obtaining clinical samples and the poor performance of diagnostic tests.