Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Emergence of methicillin resistance predates the clinical use of antibiotics

The discovery of antibiotics more than 80 years ago has led to considerable improvements in human and animal health. Although antibiotic resistance in environmental bacteria is ancient, resistance in human pathogens is thought to be a modern phenomenon that is driven by the clinical use of antibiotics(1). Here we show that particular lineages of methicillin-resistant Staphylococcus aureus-a notorious human pathogen-appeared in European hedgehogs in the pre-antibiotic era. Subsequently, these lineages spread within the local hedgehog populations and between hedgehogs and secondary hosts, including livestock and humans. We also demonstrate that the hedgehog dermatophyte Trichophyton erinacei produces two beta-lactam antibiotics that provide a natural selective environment in which methicillin-resistant S. aureus isolates have an advantage over susceptible isolates. Together, these results suggest that methicillin resistance emerged in the pre-antibiotic era as a co-evolutionary adaptation of S. aureus to the colonization of dermatophyte-infected hedgehogs. The evolution of clinically relevant antibiotic-resistance genes in wild animals and the connectivity of natural, agricultural and human ecosystems demonstrate that the use of a One Health approach is critical for our understanding and management of antibiotic resistance, which is one of the biggest threats to global health, food security and development

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Vigilancia de la resistencia a antibióticos en enfermedad invasiva por Pseudomonas aeruginosa en Galicia: 2013-2014

Introduction. The aim of this study is to know the antibiotic sensitivity of the Pseudomonas aeruginosa, which produces invasive infections in Galicia in 2013/2014, in the framework of the Surveillance Study of Antimicrobial Resistance. Methods. A total of 357 isolates of P. aeruginosa were analyzed in blood or CSF samples from 9 hospitals in Galicia. The variables were: origin, demographic data, sample type and antibiotic sensitivity. CLSI breakpoints were used. For each antibiotic we analyzed frequencies, cases/100.000 inhabitants, concordance of resistance and differences between hospitals, sex and age. Results. The majority of patients were male gender and the not-sensitives were superior in the 45 to 64 age group with significant differences to ciprofloxacin, imipenem, tobramycin and colistin. The overall not-sensitivity isolates was: piperacillin/tazobactam 18%, ciprofloxacin 28.7%, ceftazidime 17.1%, cefepime 19.7%, imipenem 23.1%, meropenem 22.1%, tobramycin 13.0%, amikacin 7.3% and colistin 4.4%. The cases/100,000 inhabitants were higher in men as age increasing. Without analyzing colistin, the 57.1% of the isolates were sensitives to other antibiotics studied (piperacillin/tazobactam, quinolones, ceftazidime, aminoglycosides, carbapenems), 19.4% were not-susceptible to only one antibiotic, 12. 2% to two, 3.7% to three, 5.1% to four and 2.0% to all antibiotics tested. Conclusions. Of the antibiotics tested, the most susceptible to P. aeruginosa were amikacin and colistin. Our data are consistent with the observed ones nationwide except colistin. Sensitivity patterns of P. aeruginosa should be periodically evaluated in each area and each hospital in order to assess the different therapeutic regimens.Introducción. El objetivo de este estudio es conocer la sensibilidad antibiótica de Pseudomonas aeruginosa productora de enfermedad invasiva en Galicia en 2013/2014, en el marco del Estudio de Vigilancia de las Resistencias Antimicrobianas. Métodos. Se analizaron 357 aislamientos de P. aeruginosa en muestras de sangre o LCR en 9 hospitales de Galicia. Las variables fueron: procedencia, datos demográficos, tipo de muestra y sensibilidad antibiótica. Se usaron puntos de corte de CLSI. Para cada antibiótico se analizaron frecuencias, casos/100.000 habitantes, concordancia de la resistencia y diferencias entre hospitales, sexo y edad. Resultados. El sexo predominante fue el masculino y la no sensibilidad superior en el grupo de 45 a 64 años con diferencias significativas a ciprofloxacino, imipenem, tobramicina y colistina. La no sensibilidad global: piperacilina/tazobactam 18%, ciprofloxacino 28’7%, ceftazidima 17’1%, cefepime 19’7%, imipenem 23’1%, meropenem 22’1%, tobramicina 13’0%; amikacina, 7’3% y colistina 4’4%. Los casos/100.000 habitantes fueron superiores en hombres según aumenta la edad. Sin analizar la colistina, el 57’1% de los aislamientos fueron sensibles a los otros grupos estudiados (piperacilina/tazobactam, quinolonas, ceftazidima, aminoglucósidos, carbapenems), el 19’4% fueron no sensibles a un antibiótico, 12’2% a dos, el 3’7% a tres, el 5’1% a cuatro y el 2’0% a todos los analizados. Conclusiones. De los antibióticos evaluados, los más activos frente a P. aeruginosa fueron amikacina y colistina. Nuestros datos concuerdan con lo observado a nivel nacional, excepto para colistina. Deben evaluarse periódicamente patrones de sensibilidad de P. aeruginosa en cada zona y cada hospital para poder valorar las diferentes pautas terapéuticas

Species and biotypes of Streptococcus bovis causing infective endocarditis

Introduction: Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes. Methods: Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes. Results: There are significant differences between the incidence of SBEC IE in HL (27.9/106) vs. HF and HB (8.8 and 7,1, respectively, p<0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p<0.01), duration of symptoms before diagnosis (46.9±46.5 vs. 30.4±40.9 days; p<0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p<0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p<0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p<0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p<0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p<0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%. Conclusions: IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains

Transcatheter Mitral Repair for Functional Mitral Regurgitation According to Left Ventricular Function: A Real-Life Propensity-Score Matched Study

Background: Transcatheter mitral valve repair (TMVR) could improve survival in functional mitral regurgitation (FMR), but it is necessary to consider the influence of left ventricular ejection fraction (LVEF). Therefore, we compare the outcomes after TMVR with Mitraclip&reg; between two groups according to LVEF. Methods: In an observational registry study, we compared the outcomes in patients with FMR who underwent TMVR with and without LVEF &lt;30%. The primary endpoint was the combined one-year all-cause mortality and unplanned hospital readmissions due to HF. The secondary end-points were New York Heart Association (NYHA) functional class and mitral regurgitation (MR) severity. Propensity-score matching was used to create two groups with the same baseline characteristics, except for baseline LVEF. Results: Among 535 FMR eligible patients, 144 patients with LVEF &lt;30% (group 1) and 144 with LVEF &gt;30% (group 2) had similar propensity scores and were included in the analyses. The primary study endpoint was significantlly higher in group 1 (33.3% vs. 9.4%, p = 0.002). There was a maintained improvement in secondary endpoints without significant differences among groups. Conclusion: FMR patients with LVEF &lt;30% treated with MitraClip&reg; had higher mortality and readmissions than patients with LVEF &ge;30% treated with the same device. However, both groups improved the NYHA functional class and MR severity

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE):an international observational study

Background: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. Methods: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. Findings: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p&lt;0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14–1·44; all p&lt;0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12–1·72) irrespective of other patient and service characteristics. Interpretation: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes