The Different Microbial Etiology of Prosthetic Joint Infections according to Route of Acquisition and Time after Prosthesis Implantation, Including the Role of Multidrug-Resistant Organisms

The aim of our study was to characterize the etiology of prosthetic joint infections (PJIs)—including multidrug-resistant organisms (MDRO)—by category of infection. A multicenter study of 2544 patients with PJIs was performed. We analyzed the causative microorganisms according to the Tsukayama’s scheme (early postoperative, late chronic, and acute hematogenous infections (EPI, LCI, AHI) and “positive intraoperative cultures” (PIC)). Non-hematogenous PJIs were also evaluated according to time since surgery: 12 months. AHIs were mostly caused by Staphylococcus aureus (39.2%) and streptococci (30.2%). EPIs were characterized by a preponderance of virulent microorganisms (S. aureus, Gram-negative bacilli (GNB), enterococci), MDROs (24%) and polymicrobial infections (27.4%). Conversely, coagulase-negative staphylococci (CoNS) and Cutibacterium species were predominant in LCIs (54.5% and 6.1%, respectively) and PICs (57.1% and 15.1%). The percentage of MDROs isolated in EPIs was more than three times the percentage isolated in LCIs (7.8%) and more than twice the proportion found in AHI (10.9%). There was a significant decreasing linear trend over the four time intervals post-surgery for virulent microorganisms, MDROs, and polymicrobial infections, and a rising trend for CoNS, streptococci and Cutibacterium spp. The observed differences have important implications for the empirical antimicrobial treatment of PJIs.Instituto de Salud Carlos IIIMinisterio de Economía y Competitividad PI15/1026European Regional Development Fund (FEDER)European Social Fund "Investing in your future"European Development Regional Fund “A way to achieve Europe

Stenotrophomonas maltophilia: estudio clínico, epidemiológico y pronóstico

Stenotrophomonas maltophilia es un patógeno emergente oportunista. Con este trabajo se pretende conocer las características clínicas de los pacientes que adquieren este microorganismo (tanto si están infectados o sólo colonizados), su epidemiología, y el pronóstico de los pacientes que tienen infecciones por este microorganismo. Se diseñó un estudio multicéntrico de casos y controles para el estudio de los factores de riesgo asociados a la adquisición de este microorganismo, y un estudio de cohorte de los pacientes que adquirieron S. maltophilia en el Hospital Virgen Macarena de Sevilla, con el que se pretendía describir la clínica asociada a las infecciones por este microorganismo, su epidemiología clínica y molecular, la sensibilidad antimicrobiana, y los factores asociados a la mortalidad, así como la respuesta a los distintos tratamientos antimicrobianos. Las conclusiones finales fundamentales del trabajo fueron: 1) S. maltophilia es un microorganismo que, en ausencia de brotes epidémicos, se encuentra en nuestros hospitales en forma de baja endemia. Las áreas de mayor incidencia son las Unidades de Cuidados Intensivos. 2) Los factores de riesgo para la adquisición de S. maltophilia son el consumo previo de carbapenemas, ceftazidima y quinolonas, y la ventilación mecánica, así como la duración de los mismos. 3) En algunas ocasiones, incrementos en el número de casos de colonización o infección por S. maltophilia en unidades de hospitalización específicas, pueden estar asociados a incrementos en el consumo de carbapenemas. 4) Existe una gran variabilidad genética en S. maltophilia que no se corresponde con la gran homogeneidad de la sensibilidad antimicrobiana de las cepas. Aunque se ha demostrado la transmisión cruzada de forma ocasional, nuestros datos sugieren que la forma más habitual de transmisión del microorganismo podría estar en relación con la adquisición independiente desde diversas fuentes ambientales. 5) Trimetoprim-sulfametoxazol continúa siendo uno de los fármacos más activos in vitro frente a S. maltophilia. Doxiciclina fue el fármaco más activo (100% de las cepas sensibles). Las nuevas fluoroquinolonas, como moxifloxacino, son fármacos con buenas expectativas para el tratamiento. 6) Entre los pacientes que adquieren S. maltophilia en nuestro estudio, la administración previa de ceftazidima y el no estar ingresado en UCI se asociaron a la presencia de infección por este microorganismo. 7) S. maltophilia produce un amplio espectro clínico de infecciones, fundamentalmente nosocomiales, y en pacientes predispuestos. Las infecciones más frecuentes son las del tracto respiratorio inferior, sobre todo neumonías. Estas ocurren en pacientes severamente enfermos, tienen un curso clínico grave y se asocian a una elevada mortalidad. En general, el resto de las infecciones evolucionan favorablemente con un tratamiento antimicrobiano adecuado, drenaje quirúrgico o limpieza de heridas y abscesos, y retirada de dispositivos invasivos. 8) La adquisición nosocomial de S. maltophilia no parece suponer un marcador de riesgo de mortalidad hospitalaria. El pronóstico de la mayoría de las infecciones producidas por S. maltophilia es favorable. Los factores de riesgo asociados a la mortalidad en los pacientes que adquieren S. maltophilia están relacionados con la edad y la severidad de su enfermedad de base. La mortalidad asociada a la infección por S. maltophilia está relacionada con la edad y la neumonía (50% de las muertes).Premio Extraordinario de Doctorado U

Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride

[EN] The synthesis of capped mesoporous silica nanoparticles (MSN) conjugated with an antibody (AB) as a gatekeeper has been carried out in order to obtain a delivery system able to release an entrapped cargo (dye) in the presence of a target molecule (antigen) to which the conjugated antibody binds selectively. In particular, MSN loaded with rhodamine B and functionalized on the external surface with a suitable derivative of N-(t-butyl)- 3-oxo-(5a,17b)-4-aza-androst-1-ene-17-carboxamide (finasteride) have been prepared (S1). The addition of polyclonal antibodies against finasteride induced capping of the pores due to the interaction with the anchored hapten-like finasteride derivative to give a MSN¿hapten¿AB nanoparticle S1-AB. It was found that the addition of capped material S1-AB to water solutions containing finasteride resulted in displacement of the antibody, pore uncapping and entrapped-dye release. The response of the gated material is highly selective, and only finasteride, among other steroids, was able to induce a significant uncapping process. Compared with finasteride, the finasteride metabolite was able to release 17% of the dye, whereas the exogen steroids testosterone, metenolone and 16-b-hydroxystanozolol only induced very little release of rhodamine B (lower than 10%) from aqueous suspensions containing sensing solid S1-AB. A detection limit as low as 20 ppb was found for the fluorimetric detection of finasteride. In order to evaluate a possible application of the material for label-free detection of finasteride, the capped material was isolated and stored to give final sensing solid S1-AB-i. It was found to display a similar behavior towards finasteride as to that shown by freshly prepared S1-AB; even after a period of two months, no significant loss of selectivity or sensitivity was noted. Moreover, to study the application for the detection of finasteride in biological samples, this ¿aged¿ material, S1-AB-i, was tested using commercially available blank urine as matrix. Samples containing 70 and 90% blank urine were spiked with a defined amount of finasteride, and the concentration was determined using capped S1-AB-i. Recovery ranges from 94% to 118% were reached.Financial support from the Spanish Government (project MAT2009-14564-C04-01) and the Generalitat Valenciana (Spain) (projects PROMETEO/2009/016 and PROMETEO/2010/008) is gratefully acknowledged. E. C. thanks the Minesterio de Ciencia e Innovacion (MICINN, Spain) for her fellowship.Climent Terol, E.; Martínez Mañez, R.; Maquieira Catala, Á.; Sancenón Galarza, F.; Marcos Martínez, MD.; Brun Sánchez, EM.; Soto Camino, J.... (2012). Antibody-Capped Mesoporous Nanoscopic Materials:Design of a Probe for the Selective Chromo-FluorogenicDetection of Finasteride. ChemistryOpen. 1:251-259. https://doi.org/10.1002/open.201100008S251259

Hybrid materials with nanoscopic anion-binding pockets for the colorimetric sensing of phosphate in water using displacement assays

Mesoporous amino-functionalised solids containing certain dyes have been used as suitable anion hosts in displacement assays for the colorimetric signalling of phosphate in water.Amoros del Toro, Pedro Jose, [email protected]

UV-induced degradation of securin is mediated by SKP1-CUL1-βTrCP E3 ubiquitin ligase

Securin is a chaperone protein with bifunctional properties. It binds to separase to inhibit premature sister chromatid separation until the onset of anaphase, and it also takes part in cell-cycle arrest after UV irradiation. At metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome (APC/C), allowing activation of separase. However, although securin is reported to undergo proteasome-dependent degradation after UV irradiation, the ubiquitin ligase responsible for securing ubiquitylation has not been well characterized. In this study, we show that UV radiation induced a marked reduction of securin in both the nucleus and cytoplasm. Moreover, we show that GSK-3β inhibitors prevent securin degradation, and that CUL1 and βTrCP are involved in this depletion. We also confirmed that SKP1-CUL1-βTrCP (SCFβTrCP) ubiquitylates securin in vivo, and identified a conserved and unconventional βTrCP recognition motif (DDAYPE) in the securin primary amino acid sequence of humans, nonhuman primates and rodents. Furthermore, downregulation of βTrCP caused an accumulation of securin in non-irradiated cells. We conclude that SCFβTrCP is the E3 ubiquitin ligase responsible for securing degradation after UV irradiation, and that it is involved in securin turnover in nonstressed cells.Ministerio de Educación y Ciencia SAF 2005-07713-C03-0

Nanoscopic hybrid systems with a polarity-controlled gate-like scaffolding for the colorimetric signalling of long-chain carboxylates

Hybrid mesoporous systems containing a gate-like ensemble functionalised with imidazolium groups and a dye are used for the selective colorimetric sensing of long-chain carboxylates.Amoros del Toro, Pedro Jose, [email protected]

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial

[Purpose] To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture.[Methods] Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB. Primary outcome: early-PJI after HHA.[Results] Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33–3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15–7.10]). [Conclusions] Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47.This work was supported by the Spanish Clinical Research Network (SCReN), co-finaced by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, through the project PI15/02161 and by the Plan Nacional de I+D+i 2013-016 and ISCIIII, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)-co-financed by European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014-2020.Peer reviewe

Supramolecular self-assembling in mesostructured materials through charge tuning in the inorganic phase

Supramolecular self-assembling of organic CTA+ micelles and inorganic [VO(H2O)PO4]n^q-2 2D-anions for the isolation of hexagonal mesostructured materials can be reached by charge tuning in the inorganic phase through the adjustment of the vanadium mean oxidation state.El Haskouri, Jamal, [email protected] ; Cabrera Medina, Saul, [email protected] ; Beltran Porter, Aurelio, [email protected] ; Alamo Serrano, Jaime, [email protected] ; Beltran Porter, Daniel, [email protected] ; Amoros del Toro, Pedro Jose, [email protected]

Off-target effects of bacillus Calmette–Guerin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19

Background and objectives. Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guerin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS-CoV-2. Methods. This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with c-irradiated SARS CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry. Results. BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-a and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS-CoV-2. Conclusions. The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19

Long-Term Control of Endemic Hospital-Wide Methicillin-Resistant Staphylococcus aureus (MRSA): The Impact of Targeted Active Surveillance for MRSA in Patients and Healthcare Workers

To evaluate the long-term impact of successive interventions on rates of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection and MRSA bacteremia in an endemic hospital-wide situation. DESIGN:Quasi-experimental, interrupted time-series analysis. The impact of the interventions was analyzed by use of segmented regression. Representative MRSA isolates were typed by use of pulsed-field gel electrophoresis. SETTING:A 950-bed teaching hospital in Seville, Spain. PATIENTS:All patients admitted to the hospital during the period from 1995 through 2008. METHODS:Three successive interventions were studied: (1) contact precautions, with no active surveillance for MRSA; (2) targeted active surveillance for MRSA in patients and healthcare workers in specific wards, prioritized according to clinical epidemiology data; and (3) targeted active surveillance for MRSA in patients admitted from other medical centers. RESULTS:Neither the preintervention rate of MRSA colonization or infection (0.56 cases per 1,000 patient-days [95% confidence interval {CI}, 0.49-0.62 cases per 1,000 patient-days]) nor the slope for the rate of MRSA colonization or infection changed significantly after the first intervention. The rate decreased significantly to 0.28 cases per 1,000 patient-days (95% CI, 0.17-0.40 cases per 1,000 patient-days) after the second intervention and to 0.07 cases per 1,000 patient-days (95% CI, 0.06-0.08 cases per 1,000 patient-days) after the third intervention, and the rate remained at a similar level for 8 years. The MRSA bacteremia rate decreased by 80%, whereas the rate of bacteremia due to methicillin-susceptible S. aureus did not change. Eighty-three percent of the MRSA isolates identified were clonally related. All MRSA isolates obtained from healthcare workers were clonally related to those recovered from patients who were in their care. CONCLUSION:Our data indicate that long-term control of endemic MRSA is feasible in tertiary care centers. The use of targeted active surveillance for MRSA in patients and healthcare workers in specific wards (identified by means of analysis of clinical epidemiology data) and the use of decolonization were key to the success of the program