Association of microbiological factors with mortality in Escherichia coli bacteraemia presenting with sepsis/septic shock: a prospective cohort study.

OBJECTIVES: This study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock). METHODS: Whole-genome sequencing was performed on 224 E coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance, and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). RESULTS: Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02-1.07), Charlson index ≥3 (1.78; 0.95-3.32), urinary BSI source (0.30; 0.16-0.57), and active empirical treatment (0.36; 0.11-1.14) with an AUROC of 0.73 (95% CI, 0.67-0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94-14.04), eilA gene (2.62; 1.14-6.02), and astA gene (2.39; 0.87-6.59) as associated with mortality, with an AUROC of 0.76 (0.69-0.82). DISCUSSION: Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and deserve to be studied as potential therapeutic or preventive targets.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study.

BACKGROUND: Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. METHODS: E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shock criteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A, B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. FINDINGS: We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. INTERPRETATION: In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. FUNDING: Instituto de Salud Carlos III.

Randomised, open-label, non-inferiority clinical trial on the efficacy and safety of a 7-day vs 14-day course of antibiotic treatment for uncomplicated enterococcal bacteraemia: the INTENSE trial protocol.

INTRODUCTION: Enterococcus spp is responsible for 8%-15% of total bacteraemias with an associated global mortality around 23%-30%. Regarding the clinical management of enterococcal bacteraemia, the evidence on the duration of antibiotic treatment is scarce and the studies do not discriminate between complicated and uncomplicated bacteraemia. METHODS: The INTENSE study is a multicentre, open-label, randomised, pragmatic, phase-IV clinical trial to demonstrate the non-inferiority of a 7-day vs 14-day course for the treatment of uncomplicated enterococcal bacteraemia and incorporating the early switching to oral antibiotics when feasible. The primary efficacy endpoint is the clinical cure at day 30±2 after the end of the treatment. Secondary endpoints will include the rate of relapse or infective endocarditis, length of stay, duration of intravenous therapy, Clostridioides difficile infection and the evaluation of the safety of both treatment arms through the recording and analysis of adverse events. For a 6% non-inferiority margin and considering a 5% withdrawal rate, 284 patients will be included. ANALYSIS: The difference in proportions with one-sided 95% CIs will be calculated for the clinical cure rate using the control group as reference. For secondary categorical endpoints, a similar analysis will be performed and Mann-Whitney U-test will be used to compare median values of quantitative variables. A superiority analysis applying the response adjusted for days of antibiotic risk will be performed if there were incidents in recruitment; will allow obtaining results with 194 patients recruited. ETHICS AND DISSEMINATION: The study has obtained the authorisation from the Spanish Regulatory Authority, the approval of the ethics committee and the agreement of the directors of each centre. Data will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05394298.

A multi-strain probiotic promoted recovery of puppies from gastroenteritis in a randomized, double-blind, placebo-controlled study.

Objective and animals: Acute diarrhea is among the most common causes of veterinary consultations for dogs. A double-blind, placebocontrolled intervention trial was done with 120 puppies with gastroenteritis. These dogs were 1 to 4 mo old, male and female, of various breeds and sizes. Procedure: Dogs were randomly allocated into 2 groups: Those in the treated group (TG) received a multi-strain probiotic with Lactobacillus johnsonii CRL1693, Ligilactobacillus murinus CRL1695, Limosilactobacillus mucosae CRL1696, and Ligilactobacillus salivarius CRL1702 (1 × 109 CFU/mL) daily for 7 d, whereas those in the control group (CG) received a placebo. All puppies received intravenous fluids, an antiparasitic, amoxicillin PO, and enrofloxacin SC. Results: At the start of the trial, the 2 groups were similar. Probiotic administration for 7 d normalized fecal consistency, with 69, 50, and 80% of small, medium, and large puppies in the TG achieving a fecal score of 1 (separate hard lumps) at 7 d, significantly better than puppies in the CG. After 7 d of treatment, most puppies (70%) in the TG had an excellent recovery, whereas in the CG, recoveries were 35.7% "bad" and 30.4% "fair." Therefore, treatment with probiotics hastened recovery (P < 0.0001). At the end of the trial, there was a significant increase of cultivable lactobacilli in the feces of TG puppies, but no significant differences between the 2 groups in numbers of total mesophylls, enterobacteria, or Gram-positive cocci. Total mortality was 5.8%, including 4 puppies from the CG and 3 from the TG. Conclusion: In a randomized, double-blind, placebo-controlled study, puppies with gastroenteritis symptoms receiving a multi-strain probiotic had rapid improvement, implying beneficial effects on the microbiota and its functionality.

Un probiotique multi-souches a favorisé la guérison des chiots de la gastro-entérite dans une étude randomisée, en double aveugle et vérifiée par placebo. Objectif et animaux: La diarrhée aiguë fait partie des causes les plus fréquentes de consultations vétérinaires pour les chiens. Un essai d'intervention en double aveugle et vérifié par placebo a été réalisé avec 120 chiots atteints de gastro-entérite. Ces chiens étaient âgés de 1 à 4 mois, mâles et femelles, de différentes races et tailles. Procédure: Les chiens ont été répartis au hasard en 2 groupes : ceux du groupe traité (TG) ont reçu un probiotique multisouches contenant Lactobacillus johnsonii CRL1693, Ligilactobacillus murinus CRL1695, Limosilactobacillus mucosae CRL1696 et Ligilactobacillus salivarius CRL1702 (1 × 109 UFC/mL) quotidiennement pendant 7 j, tandis que ceux du groupe témoin (CG) ont reçu un placebo. Tous les chiots ont reçu des liquides intraveineux, un antiparasitaire, de l'amoxicilline PO et de l'enrofloxacine SC. Résultats: Au début de l'essai, les 2 groupes étaient similaires. L'administration de probiotiques pour une durée de 7 j a normalisé la consistance fécale, avec 69, 50 et 80 % des chiots petits, moyens et grands dans le TG obtenant un score fécal de 1 (morceaux durs séparés) à 7 jours, ce qui était significativement meilleur que les chiots dans le CG. Après 7 jours de traitement, la plupart des chiots (70 %) dans le TG ont eu une excellente récupération, alors que dans le CG, les récupérations étaient de 35,7 % « mauvaises ¼ et 30,4 % « passables ¼. Par conséquent, le traitement avec des probiotiques a accéléré la récupération (P < 0,0001). À la fin de l'essai, il y avait une augmentation significative des lactobacilles cultivables dans les fèces des chiots TG, mais aucune différence significative entre les 2 groupes en nombre de mésophylles totaux, d'entérobactéries ou de coques à Gram positif. La mortalité totale était de 5,8 %, dont 4 chiots du CG et 3 du TG. Conclusion: Dans une étude randomisée, en double aveugle et vérifiée par placebo, des chiots présentant des symptômes de gastro-entérite recevant un probiotique multi-souches ont présenté une amélioration rapide, impliquant des effets bénéfiques sur le microbiote et sa fonctionnalité.(Traduit par Dr Serge Messier).

Effect of probiotic lactobacilli supplementation on growth parameters, blood profile, productive performance, and fecal microbiology in feedlot cattle.

Lactic acid bacteria (LAB) selected on the basis of probiotic characteristics were administered to beef feedlot catlle and the effect on body condition/growth and nutritional-metabolic status as well as on E. coli O157:H7 fecal shedding, were investigated. A feeding trials involving 126 steers were used to evaluate the effects of Lactobacillus acidophilus CRL2074, Limosilactobacillus fermentum CRL2085 and Limosilactobacillus mucosae CRL2069 and their combinations (5 different probiotic groups and control) when 107-108 CFU/animal of each probiotic group were in-feed supplemented. Cattle were fed a high energy corn-based diet (16 to 88%) and samples from each animal were taken at 0, 40, 104 and 163 days. In general, animals body condition and sensorium state showed optimal muscle-skeletal development and behavioral adaption to confinement; no nasal/eye discharges and diarrheic feces were observed. The nutritional performance of the steers revealed a steady increase of biometric parameters and weight. Animals supplied with L. mucosae CRL2069 for 104 days reached the maximum mean live weight (343.2 kg), whereas the greatest weight daily gain (1.27 ± 0.16 Kg/day) was obtained when CRL2069 and its combination with L. fermentum CRL2085 (1.26 ± 0.11 kg/day) were administered during the complete fattening cycle. With several exceptions, bovine cattle blood and serum parameters showed values within referential ranges. As a preharvest strategy to reduce Escherichia coli O157:H7 in cattle feces, CRL2085 administered during 40 days decreased pathogen shedding with a reduction of 43% during the feeding period. L. fermentum CRL2085 and L. mucosae CRL2069 show promise for feedlot cattle feeding supplementation to improve metabolic-nutritional status, overall productive performance and to reduce E. coli O157:H7 shedding, thus decreasing contamination chances of meat food products.

Predictors of clinical evolution of SARS-CoV-2 infection in hematological patients: A systematic review and meta-analysis.

Main aim of this systematic review is to quantify the risk and identify predictors of clinical evolution of SARS-CoV-2 in hematological patients compared to different control populations. Two independent reviewers screened the literature assessing clinical outcomes of SARS-CoV-2 infection in adult patients with active hematological malignancies published up to June 2021. Primary outcome was COVID-19 related mortality, secondary outcomes were hospital and intensive-care admission, mechanical ventilation (MV), and thromboembolic events. Variables related to study setting, baseline patients' demographic, comorbidities, underlying hematological disease, ongoing chemotherapy, COVID-19 presentation, and treatments were extracted. A total of 67 studies including 10,061 hematological patients and 111,143 controls were included. Most of the studies were retrospective cohorts (51 studies, 76%) and only 19 (13%) provided data for a control group. A significant increased risk of clinical progression in the hematological population compared to the controls was found in terms of COVID-19 related mortality (OR, 2.12; 95% CI, 1.77-2.54), hospitalization (OR, 1.98; 95% CI, 1.15-3.43), intensive-care admission (OR, 1.77; 95% CI, 1.38-2.26), and MV (OR, 2.17; 95% CI, 1.71-2.75). The risk remained significantly higher in the subgroup analysis comparing hematological patients versus solid cancer. Meta-regression analysis of uncontrolled studies showed that older age, male sex, and hypertension were significantly related to worse clinical outcomes of COVID-19 in hematological population. Older age and hypertension were found to be associated also to thromboembolic events. In conclusion, hematological patients have a higher risk of COVID-19 clinical progression compared to both the general population and to patients with solid cancer.

Association of Patients' Epidemiological Characteristics and Comorbidities with Severity and Related Mortality Risk of SARS-CoV-2 Infection: Results of an Umbrella Systematic Review and Meta-Analysis.

The objective of this study was to assess the association between patients' epidemiological characteristics and comorbidities with SARS-CoV-2 infection severity and related mortality risk. An umbrella systematic review, including a meta-analysis examining the association between patients' underlying conditions and severity (defined as need for hospitalization) and mortality of COVID-19, was performed. Studies were included if they reported pooled risk estimates of at least three underlying determinants for hospitalization, critical disease (ICU admission, mechanical ventilation), and hospital mortality in patients diagnosed with SARS-CoV-2 infection. Evidence was summarized as pooled odds ratios (pOR) for disease outcomes with 95% confidence intervals (95% CI). Sixteen systematic reviews investigating the possible associations of comorbidities with severity or death from COVID-19 disease were included. Hospitalization was associated with age > 60 years (pOR 3.50; 95% CI 2.97−4.36), smoking habit (pOR 3.50; 95% CI 2.97−4.36), and chronic pulmonary disease (pOR 2.94; 95% CI 2.14−4.04). Chronic pulmonary disease (pOR 2.82; 95% CI 1.92−4.14), cerebrovascular disease (pOR 2.74; 95% CI 1.59−4.74), and cardiovascular disease (pOR 2.44; 95% CI 1.97−3.01) were likely to be associated with increased risk of critical COVID-19. The highest risk of mortality was associated with cardiovascular disease (pOR 3.59; 95% CI 2.83−4.56), cerebrovascular disease (pOR 3.11; 95% CI 2.35−4.11), and chronic renal disease (pOR 3.02; 95% CI 2.61−3.49). In conclusion, this umbrella systematic review provides a comprehensive summary of meta-analyses examining the impact of patients' characteristics on COVID-19 outcomes. Elderly patients and those cardiovascular, cerebrovascular, and chronic renal disease should be prioritized for pre-exposure and post-exposure prophylaxis and early treatment.

Changes in Antimicrobial Resistance and Etiology of Blood Culture Isolates: Results of a Decade (2010-2019) of Surveillance in a Northern Region of Colombia.

Background: Bloodstream infections (BSI) are important causes of morbidity and mortality worldwide. Antimicrobial surveillance is essential for identifying emerging resistance and generating empirical treatment guides, the purpose of this study is to analyze trends in antimicrobial susceptibility of BSI from 2010 to 2019 in healthcare institutions from Medellin and nearby towns in Colombia. Methods: A Whonet database was analyzed from the GERMEN antimicrobial surveillance network; frequency and antibiotic susceptibility trends were calculated on more frequent microorganisms using Mann Kendall and Sen's Slope Estimator Test. Results: 61,299 isolates were included; the three microorganisms more frequent showed a significant increasing trend through time E. coli (Sen's Slope estimator = 0.7 p = <0.01) S. aureus (Sen's Slope estimator = 0.60 p = <0.01) and K. pneumonia (Sen's Slope estimator = 0.30 p = <0.01). E. coli showed a significant increase trend in cefepime and ceftazidime resistance, while K. pneumoniae showed a significant increase in resistance to cefepime, ciprofloxacin, and gentamicin. P. aeruginosa increases its susceptibility to all analyzed antibiotics and S. aureus to oxacillin. No increasing trend was observed for carbapenem resistance. Conclusion: An upward trends was observed in more frequent microorganisms and resistance to third and fourth-generation cephalosporins for E. coli and K pneumoniae; in contrast, not increasing trends in antibiotic resistance was observed for P. aeruginosa and S. aureus. The essential role of AMR-surveillance programs is to point out and identify these trends, which should improve antibiotic resistance control.

Evidencias de validez del Inventario NEO-FFI en adultos mayores colombianos / Validity evidence of the Inventory NEO-FFI in Colombian older adults

Resumen El uso de instrumentos para evaluar la personalidad es una práctica común en psicología, de ahí que su validación y adaptación a diferentes grupos poblacionales sea fundamental. El objetivo de la presente investigación fue evaluar la validez de constructo del NEO Five Factor Inventory (NEO-FFI) en un grupo de 617 personas adultas mayores en Bogotá, Colombia. Se realizaron análisis factoriales confirmatorios, así como un análisis bifactorial. Los resultados mostraron que el inventario no logra un ajuste adecuado en ninguno de los modelos de primer orden, ni en el modelo bifactorial, como tampoco en el análisis de los factores por separado. Solamente, presentó un ajuste adecuado en los modelos AFC modificados que evalúan cada factor como individual, a excepción del factor Amabilidad. Precisamente, los ítems que tuvieron bajas cargas factoriales son aquellos ítems negativos o reversos, y, dado que la comprensión de este tipo de ítems requiere de mejores habilidades lingüísticas, se infiere que el bajo nivel educativo de las personas que conformaron la muestra pudo interferir en el logro de un ajuste adecuado de los modelos; en consecuencia, se recomienda estudiar este aspecto en futuras investigaciones.

Abstract The use of instruments to assess personality is a common practice in psychology, therefore its validation and adaptation to different population groups is fundamental. The aim of the current research was to evaluate the construct validity of the NEO-FFI Inventory in a group of 617 elderly people in Bogotá, Colombia. First ordered confirmatory factor analyses and bi-factor models were performed. The results showed that the Inventory does not achieve an adequate adjustment in any of the first-order models, nor in the bi-factorial model, nor in the analysis of the factors separately. Only in the modified CFA models that evaluate each factor individually, with the exception of Agreeableness, an adequate fit was achieved. The items registering low factor loadings are especially those negative or reverse items, and since the understanding this type of items requires better linguistic skills, it is inferred that the low educational level of the sample could interfere in achieving an adequate adjustment of the models. Consequently, it is recommended to study this aspect in future research.

Role of inorganic phosphate concentrations in in vitro activity of fosfomycin.

OBJECTIVES: The objective of this study was to evaluate the in vitro activity of fosfomycin under different physiological concentrations of inorganic phosphate (Pi). METHODS: The wild-type BW25113 strain, four isogenic mutants (ΔglpT, ΔuhpT, ΔglpT-uhpT, and ΔphoB) and six clinical isolates of Escherichia coli with different fosfomycin susceptibilities were used. EUCAST breakpoints were used. Susceptibility was evaluated by agar dilution using standard Mueller-Hinton agar (Pi concentration of 1 mM similar to human plasma concentration) and supplemented with Pi (13 and 42 mM, minimum and maximum urinary Pi concentrations) and/or glucose-6-phosphate (25 mg/L). Fosfomycin transporter promoter activity was assayed using PglpT::gfpmut2 or PuhpT::gfpmut2 promoter fusions in standard Mueller-Hinton Broth (MHB), supplemented with Pi (13 or 42 mM) ± glucose-6-phosphate. Fosfomycin activity was quantified, estimating fosfomycin EC50 under different Pi concentrations (1, 13 and 42 mM + glucose-6-phosphate) and in time-kill assays using fosfomycin concentrations of 307 (maximum plasma concentration (Cmax)), 1053 and 4415 mg/L (urine Cmax range), using MHB with 28 mM Pi (mean urine Pi concentration) + 25 mg/L glucose-6-phosphate. RESULTS: All the strains showed decreased susceptibility to fosfomycin linked to increased Pi concentrations: 1-4 log2 dilution differences from 1 to 13 mM, and 1-8 log2 dilution differences at 42 mM Pi. Changes in phosphate concentration did not affect the expression of fosfomycin transporters. By increasing Pi concentrations higher fosfomycin EC50 bacterial viability was observed, except against ΔglpT-uhpT. The increase in Pi reduced the bactericidal effect of fosfomycin. DISCUSSION: Pi variations in physiological fluids may reduce fosfomycin activity against E. coli. Elevated Pi concentrations in urine may explain oral fosfomycin failure in non-wild-type but fosfomycin-susceptible E. coli strains.

COVID-19 natural herd immunity and risk of neuropsychiatric disorders / Inmunidad natural de grupo y riesgo de trastornos neuropsiquiátricos de la COVID-19

No disponible

Desarrollo y validación de un modelo diagnóstico de resistencia antimicrobiana por beta-lactamasas de espectro extendido en infecciones urinarias adquiridas en la comunidad. ¿Cómo ajustar la predicción en prevalencias variables del desenlace? La utilidad de la contracción de predictores con regresión LASSO / Development and validation of a diagnostic model of antimicrobial resistance by extended-spectrum beta-lactamases in community-acquired urinary tract infections. How to adjust the prediction in variable outcome prevalences? The usefulness of contracting predictors with LASSO regression

INTRODUCCIÓN: Para el caso de infección urinaria adquirida en la comunidad la identificación de enterobacterias con beta-lactamasas de espectro extendido (BLEE) puede optimizar las estrategias de tratamiento, control y seguimiento; sin embargo, el efecto de prevalencias variables de este patrón de resistencia ha afectado la validez externa de este tipo de modelos. OBJETIVO: Desarrollar un modelo predictor diagnóstico que ajuste el error de predicción en prevalencias variables utilizando la regresión LASSO. MÉTODOS: Se diseñó un modelo predictor diagnóstico de infección urinaria adquirida en la comunidad por enterobacterias productoras de BLEE. Se empleó un estudio de corte transversal, tanto para la construcción como para la validación. Para evaluar el efecto de la prevalencia variable del desenlace, la validación se realizó con población en la que la proporción de aislados con este mecanismo de resistencia fue menor, los participantes fueron pacientes adultos que consultaron a servicios de urgencias de dos instituciones hospitalarias de mediano nivel de complejidad de la ciudad de Medellín. Para ajustar el efecto de un medio ambiente con menor proporción de resistencia antimicrobiana, utilizamos la contracción de predictores por regresión LASSO. RESULTADOS: Se incluyeron 303 pacientes para la construcción del modelo, se evaluaron seis predictores y la validación se realizó en 220 pacientes. CONCLUSIÓN: El modelo ajustado con regresión LASSO favoreció la validez externa del modelo en poblaciones con proporción de aislados productores de BLEE en urocultivo de pacientes ambulatorio entre 11 y 16%. Este estudio brinda criterios para un aislamiento temprano cuando los predictores están presentes en poblaciones con proporciones de resistencia en urocultivos ambulatorios cercanas a 15% y propone una metodología para ajuste de error en el diseño de modelos de predicción en resistencia antimicrobiana

BACKGROUND: In the case of community-acquired urinary tract infection, the identification of Enterobacteriaceae with extended spectrum beta-lactamases (ESBL) can optimize treatment, control and follow-up strategies, however the effect of variable prevalences of this resistance pattern has affected the external validity of this type of models. AIM: To develop a diagnostic predictive model that adjusts the prediction error in variable prevalences using the LASSO regression. METHODS: A diagnostic predictive model of community-acquired urinary tract infection by infection by ESBL producing Enterobacteriaceae was designed. A cross-sectional study was used for both construction and validation. To assess the effect of the variable prevalence of the outcome, the validation was performed with a population in which the proportion of isolates with this resistance mechanism was lower, the participants were adult patients who consulted the emergency services of two medium-level hospital institutions. complexity of the city of Medellin. To adjust for the effect of an environment with a lower proportion of antimicrobial resistance, we used the contraction of predictors by LASSO regression. RESULTS: 303 patients were included for the construction of the model, six predictors were evaluated and validation was carried out in 220 patients. CONCLUSION: The adjusted model with LASSO regression favored the external validity of the model in populations with a proportion of ESBL producing isolates in urine culture of outpatients between 11 and 16%. This study provides criteria for early isolation when predictors are present in populations with proportions of resistance in ambulatory urine cultures close to 15% and proposes a methodology for the adjustment of errors in the design of prediction models for antimicrobial resistance.

Quasiexperimental intervention study protocol to optimise the use of new antibiotics in Spain: the NEW_SAFE project.

INTRODUCTION: Ceftaroline, tedizolid, dalbavancin, ceftazidime-avibactam and ceftolozane-tazobactam are novel antibiotics used to treat infections caused by multidrug-resistant pathogens (MDR). Their use should be supervised and monitored as part of an antimicrobial stewardship programme (ASP). Appropriate use of the new antibiotics will be improved by including consensual indications for their use in local antibiotic guidelines, together with educational interventions providing advice to prescribers to ensure that the recommendations are clearly understood. METHODS AND ANALYSIS: This study will be implemented in two phases. First, a preliminary historical cohort (2017-2019) of patients from 13 Andalusian hospitals treated with novel antibiotics will be analysed. Second, a quasiexperimental intervention study will be developed with an interrupted time-series analysis (2020-2021). The intervention will consist of an educational interview between prescribers and ASP leaders at each hospital to reinforce the proper use of novel antibiotics. The educational intervention will be based on a consensus guideline designed and disseminated by leaders after the retrospective cohort data have been analysed. The outcomes will be acceptance of the intervention and appropriateness of prescription. Incidence of infection and colonisation with MDR organisms as well as incidence of Clostridioides difficile infection will also be analysed. Changes in prescription quality between periods and the safety profile of the antibiotics in terms of mortality rate and readmissions will also be measured. ETHICS AND DISSEMINATION: Ethical approval will be obtained from the Andalusian Coordinating Institutional Review Board. The study is being conducted in compliance with the protocol and regulatory requirements consistent with International Council of Harmonisation E6 Good Clinical Practice and the ethical principles of the latest version of the Declaration of Helsinki. The results will be published in peer-reviewed journals and disseminated at national and international conferences. TRIAL REGISTRATION NUMBER: NCT03941951; Pre-results.

Systematic literature review of the burden and outcomes of infections due to multidrug-resistant organisms in Europe: the ABOUT-MDRO project protocol.

INTRODUCTION: Despite the increasing importance of infections due to multidrug-resistant organisms (MDROs), there is a lack of comprehensive information about the burden of disease and outcomes of key infections caused by these pathogens. The aim of the ABOUT-MDRO (A systematic review on the burden and outcomes of infections due to multidrug resitant organisms) project is to provide estimations of the burden of some key infections and their outcomes caused by the target MDROs. METHODS AND ANALYSIS: A systematic literature search will be performed using MEDLINE/PubMed, Elsevier's SCOPUS, Cochrane library, Clinical trials and Web of Science, as well as the Surveillance Systems from Public Health Institutions and Scientific Societies for Antimicrobial Resistance and Healthcare-Associated Infections in Europe database of European surveillance systems, for data on prevalence/incidence, mortality and length of stay of target infections in hospitalised patients (including ventilator-associated pneumonia, hospital-acquired pneumonia, complicated intra-abdominal infections, complicated urinary tract infections, skin and soft tissue infections and bloodstream infections) and in specific populations (children, hospital wards, neutropenic patients) caused by cephalosporin-resistant or carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp., methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. The information retrieved will be tabulated and pooled estimates and 95% CIs calculated of rates and outcomes, using random effects models. Relationships between rates and outcomes in randomised control trials and epidemiological studies, and data of proportions and incidence/prevalence rates will also be analysed. The information collected in this study will be useful for identifying gaps in our knowledge in terms of incidence/prevalence and clinical outcomes of infections caused by MDROs, and for informing priorities in infection control and the research and design of appropriate studies. ETHICS AND DISSEMINATION: This study will be based on published data so we did not require ethical approval. Formal consent is not required. The results of this review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Data will be presented at international conferences and published in peer-reviewed journals. REGISTRATION DETAILS: PROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42019124185).

In vitro comparison of the accuracy of four intraoral scanners and three conventional impression methods for two neighboring implants.

PURPOSE: To determine whether the accuracy of two-implant model impressions taken with optical scanners was inferior to that of those taken with elastomeric materials. MATERIALS AND METHODS: Impressions of a resin reference model with two almost parallel implants were taken using three elastomeric impressions (closed tray technique, open tray nonsplinted technique and open tray splinted technique) and scanned with four optical scanners (CEREC Omnicam, 3M True Definition Scanner, 3Shape TRIOS3 and Carestream CS 3600). STL files of the different methods were superimposed and analyzed with control software (Geomagic Control X, 3D systems) to determine the mean deviation between scans. RESULTS: Compared to elastomeric impressions, optical impressions showed a significantly improved mean precision. TRIOS3 and CS3600 showed a significantly improved mean trueness compared to that of closed tray, CEREC Omnicam and TrueDefinition. All methods showed a certain degree of implant rotation over their axes, which was significantly higher in the closed tray and the open tray nonsplinted techniques. CONCLUSIONS: Optical impressions, taken under these in vitro conditions, showed improved accuracy compared with that of elastomeric impressions.

[Development and validation of a diagnostic model of antimicrobial resistance by extended-spectrum beta-lactamases in community-acquired urinary tract infections. How to adjust the prediction in variable outcome prevalences? The usefulness of contracting predictors with LASSO regression]. / Desarrollo y validación de un modelo diagnóstico de resistencia antimicrobiana por ß-lactamasas de espectro extendido en infecciones urinarias adquiridas en la comunidad. ¿Cómo ajustar la predicción en prevalencias variables del desenlace? La utilidad de la contracción de predictores con regresión LASSO.

BACKGROUND: In the case of community-acquired urinary tract infection, the identification of Enterobacteriaceae with extended spectrum beta-lactamases (ESBL) can optimize treatment, control and follow-up strategies, however the effect of variable prevalences of this resistance pattern has affected the external validity of this type of models. AIM: To develop a diagnostic predictive model that adjusts the prediction error in variable prevalences using the LASSO regression. METHODS: A diagnostic predictive model of community-acquired urinary tract infection by infection by ESBL producing Enterobacteriaceae was designed. A cross-sectional study was used for both construction and validation. To assess the effect of the variable prevalence of the outcome, the validation was performed with a population in which the proportion of isolates with this resistance mechanism was lower, the participants were adult patients who consulted the emergency services of two medium-level hospital institutions. complexity of the city of Medellin. To adjust for the effect of an environment with a lower proportion of antimicrobial resistance, we used the contraction of predictors by LASSO regression. RESULTS: 303 patients were included for the construction of the model, six predictors were evaluated and validation was carried out in 220 patients. CONCLUSION: The adjusted model with LASSO regression favored the external validity of the model in populations with a proportion of ESBL producing isolates in urine culture of outpatients between 11 and 16%. This study provides criteria for early isolation when predictors are present in populations with proportions of resistance in ambulatory urine cultures close to 15% and proposes a methodology for the adjustment of errors in the design of prediction models for antimicrobial resistance.

Revisión sistemática: costo-efectividad, acceso y adherencia a programas de ejercicio supervisado en pacientes con claudicación intermitente / Systematic review: cost-effectiveness, access and adherence to supervised exercise programs in patients with intermittent claudication

OBJETIVO: Determinar las razones de la escasa derivación, acceso, y adherencia a programas de ejercicio supervisado (PES) en pacientes con claudicación intermitente (CI) y la costo-efectividad de estos programas a nivel Internacional. MÉTODOS: Se utilizaron las fuentes de datos de PubMed y ScienceDirect. Se incluyeron revisiones con acceso completo, publicados desde el año 2010, que incluían como mínimo 3 artículos de tipo cuantitativo. RESULTADOS: Se incluyeron 5 Revisiones asociadas a los resultados del ejercicio supervisado, su costo-efectividad, la baja derivación y adherencia a PES de los pacientes con CI. En cuanto a la costo-efectividad los resultados indican que los PES fueron rentables con un ICER de £711 a £1.608 por QALY ganado al compararlos con ejercicio no supervisado, y al compararlos con la cirugía de revascularización (CR) no hay diferencia significativa en QALY ganados, sin embargo, el costo por QALY fue €381.694 más alto para la CR. Por otro lado, las principales razones de la subutilización de los PES, es que los pacientes se resisten a asistir, ya que involucra un esfuerzo y responsabilidad, además de tener problemas de reembolso, teniendo baja adherencia. Sumado a esto, el interés personal de los médicos por realizar intervenciones que involucran pago por servicio produce una baja derivación (45% de cirujanos en Europa refieren menos del 50% de sus pacientes). CONCLUSIÓN: Las principales dificultades para adoptar los PES serían una carencia en la destinación de recursos, falta de centros, dificultad de traslado, falta de tiempo, o de interés por parte de los pacientes, además de incentivos financieros a otras alternativas de tratamiento por sobre PES lo que limita su derivación.

OBJECTIVE: To determine the reasons for the limited derivation, access and adherence to supervised exercise programs (SEP) in patients with intermittent claudication (IC) and the cost-effectiveness of these programs internationally. METHODS: PubMed and ScienceDirect databases were searched. Revisions with full access, published since 2010, which included at least 3 quantitative type articles. RESULTS: 5 reviews were included, these were associated with the results of the supervised exercise, its cost-effectiveness, the low referral and adherence to programs of patients with IC. Regarding cost-effectiveness, the results indicated that SEP were more cost-effective with an ICER of £711 to £1.608 per QALY gained when compared with unsupervised exercise, and that when compared with revascularization surgery (RC) there was no significant difference in QALYs, however the cost per QALY was € 381.694 higher for the RC. On the other hand, the main reasons for the underutilization of SEP are that patients are reluctant to attend, since it involves effort and responsibility, in addition to having reimbursement problems, therefore having low adherence. Added to this, the personal interest of doctors in performing interventions that involve payment for service produce a low referral (45% of surgeons in Europe refer less than 50% of their patients) CONCLUSION: The main difficulties in adopting the SEP would be a lack in the allocation of resources, lack of centers, difficulty of transportation, lack of time or lack of interest from patients, in addition to financial incentives to other treatment alternatives over SEP, which limits their referral.