Poststroke Lung Infection by Opportunistic Commensal Bacteria Is Not Mediated by Their Expansion in the Gut Microbiota.

BACKGROUND: Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection. METHODS: Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments. RESULTS: Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae. CONCLUSIONS: Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection.

Minimally invasive lateral single-position surgery for multilevel degenerative lumbar spine disease: feasibility and perioperative results in a single Latin-American spine center.

INTRODUCTION: Within advances in minimally invasive spine surgery, the implementation of lateral single position (LSP) increases efficiency while limiting complications, avoiding intraoperative repositioning and diminishing surgical time. Most literature describes one-level instrumentation of the lumbar spine; this study includes the use of LSP for multilevel degenerative disease. OBJECTIVE: The objective of the article is to analyze initial clinical results and complications in the use of LSP for multiple level instrumentation in adults with lumbar degenerative disease. METHODS: A retrospective early clinical series was performed for patients who had multiple level instrumentation in LSP between August 2019 and September 2022 at the Hospital Universitario San Ignacio in Bogota, Colombia. Inclusion criteria were patients older than 18 years with symptomatic lumbar degenerative disease, undergoing any combination of multilevel anterior lumbar interbody fusion, lateral lumbar interbody fusion (LLIF) and pedicle screw fixation. RESULTS: Forty patients with an average age of 61.3 years were included, with diagnosis of multilevel degenerative spondylotic changes. Four-, three- and two-level interventions were performed in 52.5, 35 and 12.5%, respectively. Average time per level was 68.9 min, and length of hospital stay had an average of 2.4 days, with all patients starting ambulation within the first postoperative day. CONCLUSION: Procedural time and blood loss were similar to those reported in literature. No severe lesions, postoperative infections or reinterventions took place. Although it was a small number of patients and further clinical trials are needed, LSP for multiple levels is apparently safe with adequate outcomes which may improve efficiency in the operating room.

Treatment Decision-Making Preferences of Older Depressed Minority Primary Care Patients.

Little research examined the decision-making preferences of older, racially and ethnically diverse minority patients with untreated depression. The study's aims were to identify decision-making preferences and the characteristics associated with a more active preference in the decision-making process for general medical and depression treatment decisions. We assessed the preferred involvement in making general medical and depression treatment decisions of 201 older primary care patients with untreated depression. Linear regressions examined the association of sociodemographic and clinical characteristics with decision-making preference for both decision types. Majority of patients preferred shared decision-making for general medical and depression treatments. Female gender was associated with a preference for active decision-making for depression treatment. For this sample older depressed patients preferred sharing the decision-making responsibilities with physicians. To improve communication and the initiation and adherence to mental health care, physicians must consider older, minority patients' preferences for involvement in the decision-making process.

Serological response to vaccines against SARS-CoV-2 in patients with inflammatory bowel disease. / Respuesta serológica a las vacunas frente a SARS-CoV-2 en pacientes con enfermedad inflamatoria intestinal.

OBJECTIVE: To study the serological response (SR) and tolerability of COVID-19 vaccine in patients with inflammatory bowel disease (IBD) and its relation with IBD treatment and type of vaccine. METHODS: Observational, cross-sectional study in patients with IBD vaccinated against COVID-19 without known previous infection. SR was analyzed by the determination of IgG antibodies against the S1 subunit. Safety was studied using a questionnaire to identify adverse effects (AE). RESULTS: 280 patients with IBD were included. Type of vaccines: Comirnaty® 68.8%; Spikevax® 10.8%, Vaxzevria® 18.3%, Ad26.COV2-S® 2.2%. 51.3% had AE, being 100% mild. 65% developed IgG antibodies after vaccination. The SR was higher for vaccines with mRNA technology (100% Spikevax®, 68.5% Comirnaty®) compared to those based on adenovirus vector (38.0% Vaxzevria®, 33.3% Ad26.COV2-S®) (P<.001). In the multivariate analysis, SR was related to age (<60 years; OR: 3.8, 95% CI 1.9-7.0; P<.001). The SR in patients with aminosalicylates was 65.4%, 61.4% with immunosuppressants, 65.8% with anti-TNF, and 68.7% with non-anti-TNF biologicals (P=.9). CONCLUSIONS: One third of patients with IBD did not develop antibodies with the initial vaccination against SARS-CoV-2. The SR to vaccines based on mRNA technology was higher, and it was related to age (higher in younger patients). Immunosuppressants and biologicals did not decrease SR. More than half of the patients presented AD, being mild in all cases.

CD28 is expressed by macrophages with anti-inflammatory potential and limits their T-cell activating capacity.

CD28 expression is generally considered to be T lymphocyte specific. We have previously shown CD28 mRNA expression in M-CSF-dependent anti-inflammatory monocyte-derived macrophages (M-MØ), and now demonstrate that CD28 cell surface expression is higher in M-MØ than in GM-CSF-dependent macrophages, and that macrophage CD28 expression is regulated by MAFB and activin A. In vivo, CD28 was found in tumor-associated macrophages and, to a lower extent, in pro-inflammatory synovial fluid macrophages from rheumatoid arthritis patients. Analysis of mouse macrophages confirmed Cd28 expression in bone-marrow derived M-MØ. Indeed, anti-CD28 antibodies triggered ERK1/2 phosphorylation in mouse M-MØ. At the functional level, Cd28KO M-MØ exhibited a significantly higher capacity to activate the OVA-specific proliferation of OT-II CD4+ T cells than WT M-MØ, as well as enhanced LPS-induced IL-6 production. Besides, the Cd28KO M-MØ transcriptome was significantly different from WT M-MØ regarding the expression IFN response, inflammatory response, and TGF-ß signaling related gene sets. Therefore, defective CD28 expression in mouse macrophages associates to changes in gene expression profile, what might contribute to the altered functionality displayed by Cd28KO M-MØ. Thus, CD28 expression appears as a hallmark of anti-inflammatory macrophages and might be a target for immunotherapy.

PTSD is not the emblematic disorder of the COVID-19 pandemic; adjustment disorder is.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been hailed by some as the emblematic mental disorder of the COVID-19 pandemic, assuming that PTSD's life-threat criterion was met de facto. More plausible outcomes like adjustment disorder (AD) have been overlooked. METHODS: An online cross-sectional survey was launched in the initial stage of the pandemic using a convenience sample of 5 913 adults to compare the prevalence of COVID-related probable PTSD versus probable AD. The abridged Impact of Event Scale - Revised (IES-6) assessed the severity of trauma- and stressor-related symptoms over the previous week. Demographic and pandemic-related data (e.g., receiving a formal diagnosis of COVID-19, job loss, loss of loved one, confinement, material hardship) were collected. A Classification and Regression Tree analysis was conducted to uncover the pandemic experiences leading to clinical 'caseness'. Caseness was defined by a score > 9 on the IES-6 symptom measure and further characterized as PTSD or AD depending on whether the Peritraumatic Distress Inventory's life-threat item was endorsed or not. RESULTS: The participants were predominantly Caucasian (72.8%), women (79.2%), with a university degree (85%), and a mean age of 42.22 (SD = 15.24) years; 3 647 participants (61.7%; 95%CI [60.4, 63.0]) met the threshold for caseness. However, when perceived life-threat was accounted for, only 6.7% (95%CI [6.1, 7.4]) were classified as PTSD cases, and 55% (95%CI [53.7, 56.2]) as AD cases. Among the AD cases, three distinct profiles emerged marked by the following: (i) a worst personal pandemic experience eliciting intense fear, helplessness or horror (in the absence, however, of any life-threat), (ii) a pandemic experience eliciting sadness/grief, and (iii) worrying intensely about the safety of significant others. CONCLUSIONS: Studies considering the life-threat criterion as met de facto during the pandemic are confusing PTSD for AD on most counts. This misconception is obscuring the various AD-related idioms of distress that have emerged during the pandemic and the actual treatment needs.

Clinical impact of selumetinib on pediatric elephantiasis neuromatosa.

Elephantiasis neuromatosa (EN) is a rare and extreme form of plexiform neurofibroma in patients with neurofibromatosis type 1 (NF1). EN is often associated with significant morbidity and remains difficult to treat. We present a case of an 11-year-old female with NF1 whose thoracolumbar plexiform neurofibroma and lower extremity EN exhibited clinical improvement from treatment with selumetinib, a selective MEK inhibitor.

Effects of a Fish Oil Rich in Docosahexaenoic Acid on Cardiometabolic Risk Factors and Oxidative Stress in Healthy Rats.

Omega-3 polyunsaturated fatty acids are associated with a lower risk of cardiometabolic diseases. However, docosahexaenoic acid (DHA) is easily oxidized, leading to cellular damage. The present study examined the effects of an increased concentration of DHA in fish oil (80% of total fatty acids) on cardiometabolic risk factors and oxidative stress compared to coconut oil, soybean oil, and fish oil containing eicosapentaenoic acid (EPA) and DHA in a balanced ratio. Forty healthy male Sprague-Dawley rats were supplemented with corresponding oil for 10 weeks. Supplementation with the fish oil containing 80% DHA decreased plasma fat, plasma total cholesterol and muscle fat compared to the coconut oil and the soybean oil. Increasing concentrations of DHA induced incorporation of DHA and EPA in cell membranes and tissues along with a decrease in ω-6 arachidonic acid. The increase in DHA promoted lipid peroxidation, protein carbonylation and antioxidant response. Taken together, the increased concentration of DHA in fish oil reduced fat accumulation compared to the coconut oil and the soybean oil. This benefit was accompanied by high lipid peroxidation and subsequent protein carbonylation in plasma and in liver. In our healthy framework, the slightly higher carbonylation found after receiving fish oil containing 80% DHA might be a protecting mechanism, which fit with the general improvement of antioxidant defense observed in those rats.

Measuring Trauma Exposure: Count Versus Variety of Potentially Traumatic Events in a Binational Sample.

Traumatic event checklists typically ask respondents to indicate whether they have experienced particular types of potentially traumatic events (PTEs) and then sum these endorsements to gauge cumulative trauma exposure. However, the sum of these endorsements indicates the variety of PTEs respondents have experienced rather than the count of exposure events. The main objective of the present study was to explore the association between PTE count and variety to examine assumptions regarding the use of traumatic event checklists to measure cumulative trauma exposure. The limited empirical research suggests that count and variety are strongly associated; however, there may be variation in magnitude concerning whether participants' environments confer an increased or decreased risk of exposure. We present Life Event Checklist data from a large sample of Mexican and U.S. participants (n = 1,820), which allowed us to compare reports of count and variety. Count and variety were strongly correlated, Kendall's tau-b = .74, such that count accounted for 54.6% of the variance in variety. A negative binomial regression analysis revealed that this association was moderated by county and municipio homicide rate, used as a proxy for violent crime, but not by natural disaster history. Variety was more strongly associated with scores on the Posttraumatic Stress Checklist for DSM-5, Kendall's tau-b = .26, than was PTE count, Kendall's tau-b = .22, Fisher's z = -8.04, p < .001. Although there are challenges in estimating PTE counts, the present findings suggest that PTE variety is not a good proxy for cumulative trauma exposure.

Effects of Fish Oil and Grape Seed Extract Combination on Hepatic Endogenous Antioxidants and Bioactive Lipids in Diet-Induced Early Stages of Insulin Resistance in Rats.

Diacylglycerols (DAG) and ceramides have been suggested as early predictors of insulin resistance. This study was aimed to examine the combined effects of fish oil (FO) and grape seed extract (GSE) on hepatic endogenous antioxidants, DAG and ceramides in diet-induced early stages of insulin resistance. Thirty-five rats were fed one of the following diets: (1) a standard diet (STD group), (2) a high-fat high-sucrose diet (HFHS group), (3) an HFHS diet enriched with FO (FO group), (4) an HFHS diet enriched with GSE (GSE group) or (5) an HFHS diet enriched with FO and GSE (FO + GSE group). In the liver, endogenous antioxidants were measured using spectrophotometric and fluorometric techniques, and non-targeted lipidomics was conducted for the assessment of DAG and ceramides. After 24 weeks, the FO + GSE group showed increased glutathione peroxidase activity, as well as monounsaturated fatty acid and polyunsaturated fatty acid-containing DAG, and long-chain fatty acid-containing ceramides abundances compared to the STD group. The FO and GSE combination induced similar activation of the antioxidant system and bioactive lipid accumulation in the liver than the HFHS diet without supplementation. In addition, the FO and GSE combination increased the abundances of polyunsaturated fatty acid-containing DAG in the liver.

Effectiveness of Shared Decision-Making for Elderly Depressed Minority Primary Care Patients.

OBJECTIVE: The authors assessed the impact of a shared decision-making (SDM) intervention among elderly depressed minority primary care patients not currently receiving treatment. METHODS: A total of 202 English and Spanish-speaking primary care participants aged 65 and older who scored positive on the Patient Health Questionnaire-9 (≥10) were randomized at the physician level to receive a brief SDM intervention or usual care (UC). Primary analyses focused on patient adherence to either psychotherapy or antidepressant medication, and reduction in depression severity (Hamilton Depression Rating Scale) over 12 weeks. RESULTS: Patients randomized to physicians in the SDM condition were significantly more likely than patients of physicians randomized to UC to receive a mental health evaluation or initiate some form of treatment (39% versus 21%), and to adhere to psychotherapy visits over 12 weeks. There were no differences between groups in adherence to antidepressant medication or in reduction of depressive symptoms. CONCLUSION: Among untreated elderly depressed minority patients from an inner-city municipal hospital, a brief SDM intervention was associated with greater initiation and adherence to psychotherapy. However, low treatment adherence rates across both groups and the intervention's lack of impact on clinical outcomes highlight the need to provide focused and accessible mental health services to patients choosing active treatments.

Modulation of the Liver Protein Carbonylome by the Combined Effect of Marine Omega-3 PUFAs and Grape Polyphenols Supplementation in Rats Fed an Obesogenic High Fat and High Sucrose Diet.

Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases andtype 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damagebiomolecules, especially proteins. The present study was designed to investigate the effect of marineomega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins fromplasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS)diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of proteincarbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification byMS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combinationof both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in bothplasma and liver. The analysis of carbonylated protein targets, also referred to as the 'carbonylome',revealed an individual response of liver proteins to supplements and a modulatory effect on specificmetabolic pathways and processes due to, at least in part, the control exerted by the supplements on theliver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grapeseed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption ofHFHS diets.

Mechanistically different effects of fat and sugar on insulin resistance, hypertension, and gut microbiota in rats.

Insulin resistance (IR) and impaired glucose tolerance (IGT) are the first manifestations of diet-induced metabolic alterations leading to Type 2 diabetes, while hypertension is the deadliest risk factor of cardiovascular disease. The roles of dietary fat and fructose in the development of IR, IGT, and hypertension are controversial. We tested the long-term effects of an excess of fat or sucrose (fructose/glucose) on healthy male Wistar-Kyoto (WKY) rats. Fat affects IR and IGT earlier than fructose through low-grade systemic inflammation evidenced by liver inflammatory infiltration, increased levels of plasma IL-6, PGE2, and reduced levels of protective short-chain fatty acids without triggering hypertension. Increased populations of gut Enterobacteriales and Escherichia coli may contribute to systemic inflammation through the generation of lipopolysaccharides. Unlike fat, fructose induces increased levels of diacylglycerols (lipid mediators of IR) in the liver, urine F2-isoprostanes (markers of systemic oxidative stress), and uric acid, and triggers hypertension. Elevated populations of Enterobacteriales and E. coli were only detected in rats given an excess of fructose at the end of the study. Dietary fat and fructose trigger IR and IGT in clearly differentiated ways in WKY rats: early low-grade inflammation and late direct lipid toxicity, respectively; gut microbiota plays a role mainly in fat-induced IR, and hypertension is independent of inflammation-mediated IR. The results provide evidence that suggests that the combination of fat and sugar is potentially more harmful than fat or sugar alone when taken in excess.

Methotrexate limits inflammation through an A20-dependent cross-tolerance mechanism.

OBJECTIVES: Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but the mechanism of its anti-inflammatory action is not fully understood. In RA, macrophages display a proinflammatory polarisation profile that resembles granulocyte-macrophage colony-stimulating factor (GM-CSF)-differentiated macrophages and the response to MTX is only observed in thymidylate synthase+ GM-CSF-dependent macrophages. To determine the molecular basis for the MTX anti-inflammatory action, we explored toll-like receptor (TLR), RA synovial fluid (RASF) and tumour necrosis factor receptor (TNFR)-initiated signalling in MTX-exposed GM-CSF-primed macrophages. METHODS: Intracellular responses to TLR ligands, TNFα or RASF stimulation in long-term low-dose MTX-exposed human macrophages were determined through quantitative real-time PCR, western blot, ELISA and siRNA-mediated knockdown approaches. The role of MTX in vivo was assessed in patients with arthritis under MTX monotherapy and in a murine sepsis model. RESULTS: MTX conditioned macrophages towards a tolerant state, diminishing interleukin (IL)-6 and IL-1ß production in LPS, LTA, TNFα or RASF-challenged macrophages. MTX attenuated LPS-induced MAPK and NF-κB activation, and toll/IL-1R domain-containing adaptor inducing IFN-beta (TRIF1)-dependent signalling. Conversely, MTX increased the expression of the NF-κB suppressor A20 (TNFAIP3), itself a RA-susceptibility gene. Mechanistically, MTX-induced macrophage tolerance was dependent on A20, as siRNA-mediated knockdown of A20 reversed the MTX-induced reduction of IL-6 expression. In vivo, TNFAIP3 expression was significantly higher in peripheral blood cells of MTX-responsive individuals from a cohort of patients with arthritis under MTX monotherapy, whereas MTX-treated mice exhibited reduced inflammatory responses to LPS. CONCLUSIONS: MTX impairs macrophage proinflammatory responses through upregulation of A20 expression. The A20-mediated MTX-induced innate tolerance might limit inflammation in the RA synovial context, and positions A20 as a potential MTX-response biomarker.

A high-fat high-sucrose diet affects the long-term metabolic fate of grape proanthocyanidins in rats.

PURPOSE: Polyphenol metabolites are key mediators of the biological activities of polyphenols. This study aimed to evaluate the long-term effects of a high-fat high-sucrose (HFHS) diet on the metabolism of proanthocyanidins from grape seed extract (GSE). METHODS: Adult female Wistar-Kyoto rats were fed a standard (STD) or HFHS diet supplemented or not with GSE for 16 weeks. PA metabolites were determined by targeted HPLC-MS/MS analysis. RESULTS: A lower concentration of total microbial-derived PA metabolites was present in urine and the aqueous fraction of faeces in the HFHS + GSE group than in the STD + GSE group. In contrast, a tendency towards the formation of conjugated (epi)catechin metabolites in the HFHS + GSE group was observed. CONCLUSIONS: These results show that a HFHS diet significantly modifies PA metabolism, probably via: (1) a shift in microbial communities not counteracted by the polyphenols themselves; and (2) an up-regulation of hepatic enzymes.

Targeting Hepatic Protein Carbonylation and Oxidative Stress Occurring on Diet-Induced Metabolic Diseases through the Supplementation with Fish Oils.

The present study addressed the ability of long-chain ω-3 polyunsaturated fatty acids (ω-3 PUFA), i.e., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), to ameliorate liver protein damage derived from oxidative stress and induced by consumption of high-caloric diets, typical of Westernized countries. The experimental design included an animal model of Sprague-Dawley rats fed high-fat high-sucrose (HFHS) diet supplemented with ω-3 EPA and DHA for a complete hepatic proteome analysis to map carbonylated proteins involved in specific metabolic pathways. Results showed that the intake of marine ω-3 PUFA through diet significantly decreased liver protein carbonylation caused by long-term HFHS consumption and increased antioxidant system. Fish oil modulated the carbonylation level of more than twenty liver proteins involved in critical metabolic pathways, including lipid metabolism (e.g., albumin), carbohydrate metabolism (e.g., pyruvate carboxylase), detoxification process (e.g., aldehyde dehydrogenase 2), urea cycle (e.g., carbamoyl-phosphate synthase), cytoskeleton dynamics (e.g., actin), or response to oxidative stress (e.g., catalase) among others, which might be under the control of diet marine ω-3 PUFA. In parallel, fish oil significantly changed the liver fatty acid profile given by the HFHS diet, resulting in a more anti-inflammatory phenotype. In conclusion, the present study highlights the significance of marine ω-3 PUFA intake for the health of rats fed a Westernized diet by describing several key metabolic pathways which are protected in liver.

The Carbapenemase-Producing Klebsiella pneumoniae Population Is Distinct and More Clonal than the Carbapenem-Susceptible Population.

We studied in parallel the population structure of 90 carbapenemase-producing and 88 carbapenemase-susceptible Klebsiella pneumoniae isolates collected in 20 Spanish hospitals, in the context of the EuSCAPE project. Fourteen and 50 multilocus sequence types (MLSTs) were detected among the carbapenemase-producing and carbapenem-susceptible isolates, respectively. ST11 and ST15 clones were more frequent in the carbapenemase-producing group than in the carbapenemase-susceptible group (P < 0.0001). Among the members of the carbapenem-suceptible group, the cefotaxime-resistant population showed population parameters that differed between the populations of the wild-type strains and the carbapenemase producers.

Carbapenem-resistant Citrobacter spp. isolated in Spain from 2013 to 2015 produced a variety of carbapenemases including VIM-1, OXA-48, KPC-2, NDM-1 and VIM-2.

OBJECTIVES: There is little information about carbapenemase-producing (CP) Citrobacter spp. We studied the molecular epidemiology and microbiological features of CP Citrobacter spp. isolates collected in Spain (2013-15). METHODS: In total, 119 isolates suspected of being CP by the EUCAST screening cut-off values were analysed. Carbapenemases and ESBLs were characterized using PCR and sequencing. The genetic relationship among Citrobacter freundii isolates was studied by PFGE. RESULTS: Of the 119 isolates, 63 (52.9%) produced carbapenemases, of which 37 (58.7%) produced VIM-1, 20 (31.7%) produced OXA-48, 12 (19%) produced KPC-2, 2 (3.2%) produced NDM-1 and 1 (1.6%) produced VIM-2; 9 C. freundii isolates co-produced VIM-1 plus OXA-48. Fourteen isolates (22.2%) also carried ESBLs: 8 CTX-M-9 plus SHV-12, 2 CTX-M-9, 2 SHV-12 and 2 CTX-M-15. Fifty-seven isolates (90.5%) were C. freundii, 4 (6.3%) were Citrobacter koseri, 1 (1.6%) was Citrobacter amalonaticus and 1 (1.6%) was Citrobacter braakii. By EUCAST breakpoints, eight (12.7%) of the CP isolates were susceptible to the four carbapenems tested. In the 53 CP C. freundii analysed by PFGE, a total of 44 different band patterns were observed. Four PFGE clusters were identified: cluster 1 included eight isolates co-producing VIM-1 and OXA-48; blaVIM-1 was carried in a class 1 integron (intI-blaVIM-1-aacA4-dfrB1-aadA1-catB2-qacEΔ1/sul1) and blaOXA-48 was carried in a Tn1999.2 transposon. CONCLUSIONS: We observed the clonal and polyclonal spread of CP Citrobacter spp. across several Spanish geographical areas. Four species of Citrobacter spp. produced up to five carbapenemase types, including co-production of VIM-1 plus OXA-48. Some CP Citrobacter spp. isolates were susceptible to the four carbapenems tested, a finding with potential clinical implications.

A fermented milk concentrate and a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides protect suckling rats from rotavirus gastroenteritis.

Human milk contains bioactive compounds that confer a protective role against gastrointestinal infections. In order to find supplements for an infant formula able to mimic these benefits of breast-feeding, two different concepts were tested. The products consisted of the following: (1) a Bifidobacterium breve- and Streptococcus thermophilus-fermented formula and (2) a combination of short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides with pectin-derived acidic oligosaccharides. A rotavirus infection suckling rat model was used to evaluate improvements in the infectious process and in the immune response of supplemented animals. Both nutritional concepts caused amelioration of the clinical symptoms, even though this was sometimes hidden by softer stool consistency in the supplemented groups. Both products also showed certain modulation of immune response, which seemed to be enhanced earlier and was accompanied by a faster resolution of the process. The viral shedding and the in vitro blocking assay suggest that these products are able to bind the viral particles, which can result in a milder infection. In conclusion, both concepts evaluated in this study showed interesting protective properties against rotavirus infection, which deserve to be investigated further.

Rapid increase in resistance to third generation cephalosporins, imipenem and co-resistance in Klebsiella pneumoniae from isolated from 7,140 blood-cultures (2010-2014) using EARS-Net data in Spain. / Rápido aumento de la resistencia a cefalosporinas de 3a generación, imipenem y de la corresistencia en 7.140 aislados de Klebsiella pneumoniae en hemocultivos (2010-2014) según datos de EARS-Net en España.

INTRODUCTION: An analysis was made about the evolution of resistance to 3rd generation cephalosporins, imipenem, and other antibiotics in invasive isolates of Klebsiella pneumoniae (K. pneumoniae) according to the Spanish EARS-Net database (2010-2014). METHODS: Forty-two hospitals from 16 Autonomous Communities with an approximate population coverage of 33% participated. RESULTS: A total 7,140 pneumoniae corresponding to the same number of patients were studied. Overall resistance percentages (I+R) were: cefotaxime 15.8%, ceftazidime 13.7%, imipenem 1.7%, ciprofloxacin 20.1%, tobramycin 14.1%, gentamicin 10.4%, and amikacin 1.9%. Resistance to 3rd generation cephalosporins increased from 9.8% (2010) to 19% (2014); to ciprofloxacin from 15.4% (2010) to 19.6% (2014); to gentamicin from 6.2% (2010) to 10.3% (2014) and to tobramycin from 7.1% (2010) to 14.2% (2014) (p<.001 in all cases). Combined resistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides increased from 3.3% (2010) to 9.7% (2014) (p<.001). Resistance to imipenem also increased from 0.27% (2010) to 3.46% (2014) (p<.001). A total of 121 isolates were resistant to imipenem, of which 104 (86%) produced carbapenemases: 74 OXA-48, 14 VIM, 9 KPC (6 KPC-2 and 3 KPC-3), 6 IMP, and 1 GES. CONCLUSIONS: Over the 5 year period (2010-2014), resistance to 3rd generation cephalosporins in invasive K. pneumoniae in Spain has doubled. The combined resistance to 3rd generation cephalosporins, ciprofloxacin, and aminoglycosides has tripled, and imipenem resistance has increased almost 13 times, mostly due to the spread of carbapenemase-producing isolates.