Suchergebnisse

RESUMEN: El uso inadecuado de antibióticos es actualmente un problema mundial que requiere la revisión de las políticas sanitarias, dada la repercusión que tiene tanto a nivel individual como social. Es de gran importancia detectar la infección l oantes posible, identificar el foco y el patógeno causal, así como su susceptibilidad antibiótica para establecer un tratamiento antibiótico apropiado. Las resistencias a antibióticos son un problema que va aumentando tanto a nivel comunitario como hospitalario, generando una mayor morbilidad, mortalidad y gastos hospitalarios. Debido a esto en los últimos años se han creado en distintos centros hospitalarios programas de optimización de tratamientos antimicrobianos (PROA). Por otro lado, el aumento de las resistencias ha favorecido un incremento en el desarrollo y posterior comercialización de nuevas moléculas antibióticas frente a los principales microorganismos hospitalarios multirresistentes. ; ABSTRACT: The bad use of antibiotics is a growing problem in global public health that requires action by all government sectors and society in general. It is very important to detect the infection as soon as possible, identify the source of infection, causative pathogen and its antibiotic susceptibility to establish an appropriate antibiotic treatment. The antibiotic resistance is a problem that is increasing over time at Community and in hospitals, generating an increase in morbidity and mortality. Because of this, years ago, antimicrobial stewardships programs began to be created in different hospitals (called PROA in this document). On the other hand, increased resistance has favored the development and commercialization of new molecules of antibiotics against most of the multiresistant microorganisms.

During the COVID-19 pandemic, many studies have been carried out to evaluate different immune system components to search for prognostic biomarkers of the disease. A broad multiparametric antibody panel of cellular and humoral components of the innate and the adaptative immune response in patients with active SARS-CoV-2 infection has been evaluated in this study. A total of 155 patients were studied at admission into our center and were categorized according to the requirement of oxygen therapy as mild or severe (the latter being those with the requirement). The patients with severe disease were older and had high ferritin, D-dimer, C-reactive protein, troponin, interleukin-6 (IL-6) levels, and neutrophilia with lymphopenia at admission. Moreover, the patients with mild symptoms had significantly increased circulating non-classical monocytes, innate lymphoid cells, and regulatory NK cells. In contrast, severe patients had a low frequency of Th1 and regulatory T cells with increased activated and exhausted CD8 phenotype (CD8+CD38+HLADR+ and CD8+CD27-CD28-, respectively). The predictive model included age, ferritin, D-dimer, lymph counts, C4, CD8+CD27-CD28-, and non-classical monocytes in the logistic regression analysis. The model predicted severity with an area under the curve of 78%. Both innate and adaptive immune parameters could be considered potential predictive biomarkers of the prognosis of COVID-19 disease. ; Funding: This work was partially supported by the Cantabrian Government, grant number 2020UIC22-PUB-001, and by Instituto de Salud Carlos III, grant number COV20/00170.

Clinical cases of neonatal listeriosis are associated with brain disease and fetal loss due to complications in early or late pregnancy, which suggests that microglial function is altered. This is believed to be the first study to link microglial apoptosis with neonatal listeriosis and listeriosis-associated brain disease, and to propose a new nanovaccine formulation that reverses all effects of listeriosis and confers Listeria monocytogenes (LM)-specific immunity. We examined clinical cases of neonatal listeriosis in 2013–2015 and defined two useful prognostic immune biomarkers to design listeriosis vaccines: high anti-GAPDH1-22 titres and tumor necrosis factor (TNF)/ interleukin (IL)-6 ratios. Therefore, we developed a nanovaccine with gold glyconanoparticles conjugated to LM peptide 1-22 of GAPDH (Lmo2459), GNP-GAPDH1-22 nanovaccines formulated with a pro-inflammatory Toll-like receptor 2/4-targeted adjuvant. Neonates born to non-vaccinated pregnant mice with listeriosis, showed brain and vascular diseases and significant microglial dysfunction by induction of TNF-α-mediated apoptosis. This programmed TNF-mediated suicide explains LM dissemination in brains and livers and blocks production of early pro-inflammatory cytokines such as IL-1β and interferon-α/β. In contrast, neonates born to GNPGAPDH 1–22-vaccinated mothers before LM infection, did not develop listeriosis or brain diseases and had functional microglia. In nanovaccinated mothers, immune responses shifted towards Th1/IL-12 pro-inflammatory cytokine profiles and high production of anti-GAPDH1–22 antibodies, suggesting good induction of LM-specific memory ; This study was supported by IDIVAL grants API2010/03/SAF2009-08695, AIP13/2014/SAF2012- 34203 and INNVAL15/01 (to C. A-D and J.F), the Spanish Government through Plan Nacional (MINECO) (SAF2012-34203), FIPSE (ISCIII) (00-00002755-16) and CIBER-BNN (CIB16-NM009) (to C. A-D and I. G), RED RICET RD12/0018/0004 and BIOMID (ISCIII), SAF2013-42850-R (MINECO), HOMIN-317057- FP7-PEOPLE-2012-ITN (EU) (to M.F) and by the Spanish Government through Plan Nacional (MINECO) (CTQ2011-27268) (to S.P).