Enhancing pneumococcal bacteraemia diagnosis: A comparative assessment of culture-independent assays (MALDI-TOF-MS Sepsityper® module and a lateral flow inmunochromatography test).

INTRODUCTION: Pneumococcal bacteraemia is a major contributor to global morbidity and mortality. Traditional culture-based methods lack sensitivity and are time-consuming. This study aimed to assess the effectiveness of two culture-independent assays, the MALDI-TOF-MS Sepsityper® module and the lateral flow inmunochromatography test (LFICT) with the Standard F® Streptococcus pneumoniae, directly from positive blood culture (BC) bottles. METHODS: A prospective study was conducted from December 2021 to July 2022. For all BC positives for S. pneumoniae a double centrifugation protocol was implemented. The resulting pellet was subsequently processed using both techniques. RESULTS: The LFICT showed exceptional performance with 100% sensitivity and specificity, outperforming the MALDI-TOF-MS Sepsityper® module, which achieved 85.2% sensitivity and 100% specificity. Nevertheless, the combination of these assays offers a robust and comprehensive approach to diagnosis. CONCLUSIONS: The simultaneous use of both techniques offers a promising alternative that can be integrated into routine practices directly from BC samples.

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

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

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

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

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

Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.

PURPOSE: The clinical management of colorectal cancer patients has significantly improved because of the identification of novel therapeutic targets such as EGFR and VEGF. Because rapid tumor proliferation is associated with poor patient prognosis, here we characterized the transcriptional signature of rapidly proliferating colorectal cancer cells in an attempt to identify novel candidate therapeutic targets. EXPERIMENTAL DESIGN: The doubling time of 52 colorectal cancer cell lines was determined and genome-wide expression profiling of a subset of these lines was assessed by microarray analysis. We then investigated the potential of genes highly expressed in cancer cells with faster growth as new therapeutic targets. RESULTS: Faster proliferation rates were associated with microsatellite instability and poorly differentiated histology. The expression of 1,290 genes was significantly correlated with the growth rates of colorectal cancer cells. These included genes involved in cell cycle, RNA processing/splicing, and protein transport. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protoporphyrinogen oxidase (PPOX) were shown to have higher expression in faster growing cell lines and primary tumors. Pharmacologic or siRNA-based inhibition of GAPDH or PPOX reduced the growth of colon cancer cells in vitro. Moreover, using a mouse xenograft model, we show that treatment with the specific PPOX inhibitor acifluorfen significantly reduced the growth of three of the seven (42.8%) colon cancer lines investigated. CONCLUSIONS: We have characterized at the transcriptomic level the differences between colorectal cancer cells that vary in their growth rates, and identified novel candidate chemotherapeutic targets for the treatment of colorectal cancer.