Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: Retrospective, multicentre study including patients aged <20 years with PA-BSI in 4 tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multivariable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (IQR: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multidrug-resistant and 6.6% extensively drug-resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, p<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, p=0.002) than BSIs caused by carbapenem-susceptible PA. CR was associated with carbapenem treatment in the previous month (adjusted OR [aOR] 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Epidemiology and Risk Factors of Mycotic Aneurysm in Patients With Infective Endocarditis and the Impact of its Rupture in Outcomes. Analysis of a National Prospective Cohort.

Background: Several aspects of the occurrence and management of mycotic aneurysm (MA) in patients with infective endocarditis (IE) have not been studied. Objectives: To determine the incidence and factors associated with MA presence and rupture and to assess the evolution of those initially unruptured MA. Methods: Prospective multicenter cohort including all patients with definite IE between January 2008 and December 2020. Results: Of 4548 IE cases, 85 (1.9%) developed MA. Forty-six (54.1%) had intracranial MA and 39 (45.9%) extracranial MA. Rupture of MA occurred in 39 patients (45.9%). Patients with ruptured MA had higher 1-year mortality (hazard ratio, 2.33; 95% confidence interval, 1.49-3.67). Of the 55 patients with initially unruptured MA, 9 (16.4%) presented rupture after a median of 3 days (interquartile range, 1-7) after diagnosis, being more frequent in intracranial MA (32% vs 3.3%, P = .004). Of patients with initially unruptured MA, there was a trend toward better outcomes among those who received early specific intervention, including lower follow-up rupture (7.1% vs 25.0%, P = .170), higher rate of aneurysm resolution in control imaging (66.7% vs 31.3%, P = .087), lower MA-related mortality (7.1% vs 16.7%, P = .232), and lower MA-related sequalae (0% vs 27.8%, P = .045). Conclusions: MA occurred in 2% of the patients with IE. Half of the Mas occurred in an intracranial location. Their rupture is frequent and associated with poor prognosis. A significant proportion of initially unruptured aneurysms result from rupture during the first several days, being more common in intracranial aneurysms. Early specific treatment could potentially lead to better outcomes.

Production of Methyl Lactate with Sn-USY and Sn-ß: Insights into Real Hemicellulose Valorization.

Potassium exchanged Sn-ß and Sn-USY zeolites have been tested for the transformation of various aldoses (hexoses and pentoses), exhibiting outstanding catalytic activity and selectivity toward methyl lactate. Insights into the transformation pathways using reaction intermediates-dihydroxyacetone and glycolaldehyde-as substrates revealed a very high catalytic proficiency of both zeolites in aldol and retro-aldol reactions, showcasing their ability to convert small sugars into large sugars, and vice versa. This feature makes the studied Sn-zeolites outstanding catalysts for the transformation of a wide variety of sugars into a limited range of commercially valuable alkyl lactates and derivatives. [K]Sn-ß proved to be superior to [K]Sn-USY in terms of shape selectivity, exerting tight control on the distribution of produced α-hydroxy methyl esters. This shape selectivity was evident in the transformation of several complex sugar mixtures emulating different hemicelluloses-sugar cane bagasse, Scots pine, and white birch-that, despite showing very different sugar compositions, were almost exclusively converted into methyl lactate and methyl vinyl glycolate in very similar proportions. Moreover, the conversion of a real hemicellulose hydrolysate obtained from Scots pine through a simple GVL-based organosolv process confirmed the high activity and selectivity of [K]Sn-ß in the studied transformation, opening new pathways for the chemical valorization of this plentiful, but underutilized, sugar feedstock.

Systemic lupus erythematosus purtscher like retinopathy: Optical coherence tomography angiography assessment implications.

PURPOSE: to underline the importance of optical coherence tomography angiography (OCT-A) in the diagnosis, assessment of final visual outcome and better understanding of the Purtscher like retinopathy, as well as to emphasize on performing an ophthalmologic evaluation in all patients with systemic lupus erythematosus, as eye involvement is closely related with disease activity. METHODS: case report. Ophthalmologic multimodal imaging assessment of a patient short after experiencing a systemic lupus erythematosus severe outset. RESULTS: fundus examination revealed multiple cotton-wool exudates and sharp defined intraretinal white flecken lesions, concentrated in the posterior pole, which along macular edema and the context of lupus disease led to the diagnosis of Purtscher like retinopathy, raising concern about underlying disease activity. OCT-A evidenced ischemic affront in the superficial and deep vascular plexuses but also at choroidal level, preconizing a poor visual outcome. Precapillary retinal vascular stops and choroid lobular ischemic images, with a honey comb configuration in the latter, were of note. Six months after initial consultation, previously displayed ischemic images gave rise to retinal and choroidal atrophy translated into counting fingers best corrected visual acuity with the posterior ensue of retina neovascularization. CONCLUSIONS: This case proves ophthalmologic evaluation mandatory for all patients suffering from lupus and reveals OCT-A as an imaging tool of great value in the assessment of Purtscher retinopathy. To our knowledge, this would be the first report of a SLE Purtscher-like retinopathy characterized by OCT-A, matching graphically and unprecedently vascular micro-embolism stops and ischemic areas, seen as void signals, with the pathognomonic Purtscher flecken, and Paracentral Acute Middle Maculopathy (PAMM) lesions.

Determinants of Tricuspid Regurgitation Progression and Its Implications for Adequate Management.

BACKGROUND: Tricuspid regurgitation (TR) is associated with an increased mortality. Previous studies have analyzed predictors of TR progression and the clinical impact of baseline TR. However, there is a lack of evidence regarding the natural history of TR: the pattern of change and clinical impact of progression. OBJECTIVES: The authors sought to evaluate predictors of TR progression and assess the prognostic impact of TR progression. METHODS: A total of 1,843 patients with at least moderate TR were prospectively followed up with consecutive echocardiographic studies and/or clinical evaluation. All patients with less than a 2-year follow-up were excluded. Clinical and echocardiographic features, hospitalizations for heart failure, and cardiovascular death and interventions were recorded to assess their impact in TR progression. RESULTS: At a median 2.3-year follow-up, 19% of patients experienced progression. Patients with baseline moderate TR presented a rate progression of 4.9%, 10.1%, and 24.8% 1 year, 2 years, and 3 years, respectively. Older age (HR: 1.03), lower body mass index (HR: 0.95), chronic kidney disease (HR: 1.55), worse NYHA functional class (HR: 1.52), and right ventricle dilation (HR: 1.33) were independently associated with TR progression. TR progression was associated with an increase in chamber dilation as well as a decrease in ventriculoarterial coupling and in left ventricle ejection fraction (P < 0.001). TR progression was associated with an increased cardiovascular mortality and hospitalizations for heart failure (P < 0.001). CONCLUSIONS: Marked individual variability in TR progression hindered accurate follow-up. In addition, TR progression was a determinant for survival regardless of initial TR severity.

A potential transition from a concentrated to a generalized HIV epidemic: the case of Madagascar.

BACKGROUND: HIV expansion is controlled by a range of interrelated factors, including the natural history of HIV infection and socio-economical and structural factors. However, how they dynamically interact in particular contexts to drive a transition from concentrated HIV epidemics in vulnerable groups to generalized epidemics is poorly understood. We aim to explore these mechanisms, using Madagascar as a case-study. METHODS: We developed a compartmental dynamic model using available data from Madagascar, a country with a contrasting concentrated epidemic, to explore the interaction between these factors with special consideration of commercial and transactional sex as HIV-infection drivers. RESULTS: The model predicts sigmoidal-like prevalence curves with turning points within years 2020-2022, and prevalence reaching stabilization by 2033 within 9 to 24% in the studied (10 out of 11) cities, similar to high-prevalence regions in Southern Africa. The late/slow introduction of HIV and  circumcision, a widespread traditional practice in Madagascar, could have slowed down HIV propagation, but, given the key interplay between risky behaviors associated to young women and acute infections prevalence, mediated by transactional sex, the protective effect of circumcision is currently insufficient to contain the expansion of the disease in Madagascar. CONCLUSIONS: These results suggest that Madagascar may be experiencing a silent transition from a concentrated to a generalized HIV epidemic. This case-study model could help to understand how this HIV epidemic transition occurs.

Shaping the brain: The emergence of cortical structure and folding.

The cerebral cortex-the brain's covering and largest region-has increased in size and complexity in humans and supports higher cognitive functions such as language and abstract thinking. There is a growing understanding of the human cerebral cortex, including the diversity and number of cell types that it contains, as well as of the developmental mechanisms that shape cortical structure and organization. In this review, we discuss recent progress in our understanding of molecular and cellular processes, as well as mechanical forces, that regulate the folding of the cerebral cortex. Advances in human genetics, coupled with experimental modeling in gyrencephalic species, have provided insights into the central role of cortical progenitors in the gyrification and evolutionary expansion of the cerebral cortex. These studies are essential for understanding the emergence of structural and functional organization during cortical development and the pathogenesis of neurodevelopmental disorders associated with cortical malformations.

Artificial intelligence extracts key insights from legal documents to predict intimate partner femicide.

Legal documents serve as valuable repositories of information pertaining to crimes, encompassing not only legal aspects but also relevant details about criminal behaviors. To date and the best of our knowledge, no studies in the field examine legal documents for crime understanding using an Artificial Intelligence (AI) approach. The present study aims to fill this research gap by identifying relevant information available in legal documents for crime prediction using Artificial Intelligence (AI). This innovative approach will be applied to the specific crime of Intimate Partner Femicide (IPF). A total of 491 legal documents related to lethal and non-lethal violence by male-to-female intimate partners were extracted from the Vlex legal database. The information included in these documents was analyzed using AI algorithms belonging to Bayesian, functions-based, instance-based, tree-based, and rule-based classifiers. The findings demonstrate that specific information from legal documents, such as past criminal behaviors, imposed sanctions, characteristics of violence severity and frequency, as well as the environment and situation in which this crime occurs, enable the correct detection of more than three-quarters of both lethal and non-lethal violence within male-to-female intimate partner relationships. The obtained knowledge is crucial for professionals who have access to legal documents, as it can help identify high-risk IPF cases and shape strategies for preventing crime. While this study focuses on IPF, this innovative approach has the potential to be extended to other types of crimes, making it applicable and beneficial in a broader context.

Comparative transcriptomics reveals human-specific cortical features.

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.

Natural radionuclides behaviour in drinking groundwaters from Castilla y León (Spain); radiological implications.

Since the coming into force of the European Council Directive 51/2013 EURATOM and its transposition into the Spanish legislation, the presence of radioactive substances in drinking waters must be kept under surveillance to ensure that the health protection requirements are met. Driven by this regulatory framework, in an attempt to know the starting point from which to design surveillance plans, the groundwaters intended for human consumption of Castilla y León (Spain) have been radiologically characterised by using both low-level γ-ray and α-particle spectrometry to determine the activity concentration of the natural radionuclides needed to account for the indicative dose estimation. This extensive research has comprised the radiological characterisation of more than 400 drinking water samples from one of the European Union's largest regions. Furthermore, the gross α and gross ß activities have been analysed. Results showed a high geographical variability that can be related to the hydrogeological formations where the groundwaters come from. The uranium isotopes, 234U and 238U, are the main radionuclides present in the analysed drinking waters reaching values up to 2000 mBq/L, in the southwestern and western of Castilla y León, where U-rich minerals are part of the host rock. High 210Pb and 226,228Ra occurrences are found in the low permeability igneous and metasedimentary hydrogeological formations of Salamanca province. From a public health protection point of view, 4.4% of the total drinking water samples from intakes exceeded the Indicative Dose parametric value of 0.1 mSv, which is a not negligible number of samples, being very likely related to granitic and metamorphosed host rock under specific local conditions. This fact highlights the need for research and consideration of special surveillance of the groundwaters from these areas.

Analysis of >3400 worldwide eggplant accessions reveals two independent domestication events and multiple migration-diversification routes.

Eggplant (Solanum melongena) is an important Solanaceous crop, widely cultivated and consumed in Asia, the Mediterranean basin, and Southeast Europe. Its domestication centers and migration and diversification routes are still a matter of debate. We report the largest georeferenced and genotyped collection to this date for eggplant and its wild relatives, consisting of 3499 accessions from seven worldwide genebanks, originating from 105 countries in five continents. The combination of genotypic and passport data points to the existence of at least two main centers of domestication, in Southeast Asia and the Indian subcontinent, with limited genetic exchange between them. The wild and weedy eggplant ancestor S. insanum shows admixture with domesticated S. melongena, similar to what was described for other fruit-bearing Solanaceous crops such as tomato and pepper and their wild ancestors. After domestication, migration and admixture of eggplant populations from different regions have been less conspicuous with respect to tomato and pepper, thus better preserving 'local' phenotypic characteristics. The data allowed the identification of misclassified and putatively duplicated accessions, facilitating genebank management. All the genetic, phenotypic, and passport data have been deposited in the Open Access G2P-SOL database, and constitute an invaluable resource for understanding the domestication, migration and diversification of this cosmopolitan vegetable.

Quantifying the role of photoacclimation and self-facilitation for seagrass resilience to light deprivation.

Introduction: Light gradients are ubiquitous in marine systems as light reduces exponentially with depth. Seagrasses have a set of mechanisms that help them to cope with light stress gradients. Physiological photoacclimation and clonal integration help to maximize light capture and minimize carbon losses. These mechanisms can shape plants minimum light requirements (MLR), which establish critical thresholds for seagrass survival and help us predict ecosystem responses to the alarming reduction in light availability. Methods: Using the seagrass Cymodocea nodosa as a case study, we compare the MLR under different carbon model scenarios, which include photoacclimation and/or self-facilitation (based on clonal integration) and that where parameterized with values from field experiments. Results: Physiological photoacclimation conferred plants with increased tolerance to reducing light, approximately halving their MLR from 5-6% surface irradiance (SI) to ≈ 3% SI. In oligotrophic waters, this change in MLR could translate to an increase of several meters in their depth colonization limit. In addition, we show that reduced mortality rates derived from self-facilitation mechanisms (promoted by high biomass) induce bistability of seagrass meadows along the light stress gradient, leading to abrupt shifts and hysteretic behaviors at their deep limit. Discussion: The results from our models point to (i) the critical role of physiological photoacclimation in conferring greater resistance and ability to recover (i.e., resilience), to seagrasses facing light deprivation and (ii) the importance of self-facilitating reinforcing mechanisms in driving the resilience and recovery of seagrass systems exposed to severe light reduction events.

Colonization-persistence trade-offs in natural bacterial communities.

Fitness equalizing mechanisms, such as trade-offs, are recognized as one of the main factors promoting species coexistence in community ecology. However, they have rarely been explored in microbial communities. Although microbial communities are highly diverse, the coexistence of their multiple taxa is largely attributed to niche differences and high dispersal rates, following the principle 'everything is everywhere, but the environment selects'. We use a dynamical stochastic model based on the theory of island biogeography to study highly diverse bacterial communities over time across three different systems (soils, alpine lakes and shallow saline lakes). Assuming fitness equalization mechanisms, here we newly analytically derive colonization-persistence trade-offs, and report a signal of such trade-offs in natural bacterial communities. Moreover, we show that different subsets of species in the community drive this trade-off. Rare taxa, which are occasional and more likely to follow independent colonization/extinction dynamics, drive this trade-off in the aquatic communities, while the core sub-community did it in the soils. We conclude that equalizing mechanisms may be more important than previously recognized in bacterial communities. Our work also emphasizes the fundamental value of dynamical models for understanding temporal patterns and processes in highly diverse communities.

Epidemic thresholds and human mobility.

A comprehensive view of disease epidemics demands a deep understanding of the complex interplay between human behaviour and infectious diseases. Here, we propose a flexible modelling framework that brings conclusions about the influence of human mobility and disease transmission on early epidemic growth, with applicability in outbreak preparedness. We use random matrix theory to compute an epidemic threshold, equivalent to the basic reproduction number [Formula: see text], for a SIR metapopulation model. The model includes both systematic and random features of human mobility. Variations in disease transmission rates, mobility modes (i.e. commuting and migration), and connectivity strengths determine the threshold value and whether or not a disease may potentially establish in the population, as well as the local incidence distribution.

Conventional and new genetic resources for an eggplant breeding revolution.

Eggplant (Solanum melongena) is a major vegetable crop with great potential for genetic improvement owing to its large and mostly untapped genetic diversity. It is closely related to over 500 species of Solanum subgenus Leptostemonum that belong to its primary, secondary, and tertiary genepools and exhibit a wide range of characteristics useful for eggplant breeding, including traits adaptive to climate change. Germplasm banks worldwide hold more than 19 000 accessions of eggplant and related species, most of which have yet to be evaluated. Nonetheless, eggplant breeding using the cultivated S. melongena genepool has yielded significantly improved varieties. To overcome current breeding challenges and for adaptation to climate change, a qualitative leap forward in eggplant breeding is necessary. The initial findings from introgression breeding in eggplant indicate that unleashing the diversity present in its relatives can greatly contribute to eggplant breeding. The recent creation of new genetic resources such as mutant libraries, core collections, recombinant inbred lines, and sets of introgression lines will be another crucial element and will require the support of new genomics tools and biotechnological developments. The systematic utilization of eggplant genetic resources supported by international initiatives will be critical for a much-needed eggplant breeding revolution to address the challenges posed by climate change.

Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) on the diagnosis and antimicrobial treatment of infections due to carbapenem-resistant Gram-negative bacteria / Resumen ejecutivo del documento de consenso de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (SEIMC) sobre el diagnóstico y tratamiento antimicrobiano de las infecciones por bacterias gramnegativas resistentes a carbapenémicos

Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although ‘old’ antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the ‘new’ beta-lactams such as ceftazidime–avibactam, ceftolozane–tazobactam, meropenem–vaborbactam, imipenem–cilastatin–relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.(AU)

Las infecciones causadas por bacterias gramnegativas multirresistentes se han convertido en un problema mundial debido a su creciente incidencia y alta mortalidad asociada. Las bacterias resistentes a carbapenémicos como Klebsiella pneumoniae, Pseudomonas aeruginosa y Acinetobacter baumannii son las más importantes en la práctica clínica. El objetivo de este documento de consenso es actualizar las recomendaciones sobre diagnóstico y tratamiento de las infecciones causadas por estas bacterias multirresistentes. Aunque los antibióticos ‘antiguos’ como aminoglucósidos, colistina o tigeciclina se utilizan con frecuencia en el tratamiento de estas bacterias, los ‘nuevos’ betalactámicos como ceftazidima-avibactam, ceftolozano-tazobactam, meropenem-vaborbactam, imipenem-cilastatina-relebactam o cefiderocol se están convirtiendo de forma progresiva en el tratamiento de primera elección para la mayoría de estos microorganismos. La Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica ha designado un grupo de expertos en la materia para elaborar una guía de recomendaciones basadas en la evidencia sobre las cuestiones clínicas más habituales. Este documento está principalmente centrado en el diagnóstico microbiológico, el manejo clínico y el tratamiento dirigido de estas infecciones, con especial referencia a definir el papel de los nuevos antimicrobianos en el tratamiento de estas bacterias.(AU)

Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP).

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

Clinical impact of time to results from the microbiology laboratory in bloodstream infections caused by carbapenemase-producing Enterobacterales (TIME-CPE STUDY).

OBJECTIVES: To evaluate the impact of time to results (TTR) on the outcome of patients with carbapenemase-producing Enterobacterales bloodstream infections (CPE-BSI). METHODS: Times-series study conducted from January 2014 to December 2021, selecting patients with first CPE-BSI episodes. Periods of intervention were defined according to implementation of diagnostic bundle tests in the microbiology laboratory: pre-intervention (January 2014-December 2017) and post-intervention (January 2018-December 2021). TTR was defined as time elapsed from positivity time of the blood culture bottles to physicians' notification of CPE-BSI episodes, and was evaluated in patients who received inappropriate empirical and switched to appropriate targeted treatment (switch group). Analysis of a composite unfavourable outcome (mortality at Day 30 and/or persistent and/or recurrent bacteraemia) was performed for the total episodes and in the switch group. RESULTS: One hundred and nine episodes were analysed: 66 pre-intervention and 43 post-intervention. Compared with pre-intervention, patients in the post-intervention period were younger (68 versus 63 years, P = 0.04), had INCREMENT score > 7 (31.8% versus 53.5%, P = 0.02) and unfavourable outcome (37.9% versus 20.9%, P = 0.04). Proportion of TTR > 30 h was more frequent pre-intervention than post-intervention (61.7% versus 35.5%, P = 0.02). In multivariate analysis of the 109 episodes, source other than urinary or biliary (OR 2.76, 95% CI 1.11-6.86) was associated with unfavourable outcome, while targeted appropriate treatment trended to being protective (OR 0.17, 95% CI 0.03-1.00). Considering the switch group (n = 78), source other than urinary or biliary (OR 14.9, 95% CI 3.25-69.05) and TTR > 30 h (OR 4.72, 95% CI 1.29-17.22) were associated with unfavourable outcome. CONCLUSIONS: Decreased TTR in the post-intervention period was associated with the outcome in patients with CPE-BSI episodes.

Documento de consenso de manejo de neutropenia febril en el paciente pediátrico oncohematológico de la Sociedad Española de Infectología Pediátrica (SEIP) y la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP) / Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP)

La neutropenia febril es una de las principales complicaciones infecciosas que sufren los pacientes pediátricos oncohematológicos, y a pesar los avances en diagnóstico y tratamiento, siguen condicionando una mortalidad y morbilidad significativa. Estos pacientes agrupan una serie de factores de riesgo de infección, donde destaca la neutropenia asociada a quimioterapia, la disrupción de barreras cutáneo-mucosas y el uso de dispositivos intravasculares. El abordaje diagnóstico y terapéutico precoz de los episodios de neutropenia febril en los pacientes oncohematológicos, ajustado a las características individuales de cada paciente, es fundamental para mejorar su pronóstico. Por ello, diseñar protocolos de abordaje, que sistematicen su atención, permite optimizar y homogeneizar su abordaje. Además, racionalizar el uso de los antimicrobianos, ajustando la duración y el espectro de los mismos, es crucial para hacer frente al incremento de resistencias a antimicrobianos. El objetivo de este documento, elaborado entre la Sociedad Española de Infectología Pediátrica y la Sociedad Española de Hematología y Oncología Pediátrica, es dar recomendaciones de consenso sobre el manejo de la neutropenia febril en el paciente oncohematológico, respecto al abordaje inicial, terapia secuencial y de soporte e infección fúngica invasiva, que cada centro debe adaptar a las características de sus pacientes y epidemiología local. (AU)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance. The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends. (AU)