Risk factors and outcome associated with the acquisition of linezolid-resistant Enterococcus faecalis

Objectives: Linezolid is a synthetic oxazolidinone antibiotic frequently used to treat vancomycin-resistant enterococcal infections. Vancomycin-susceptible Enterococcus faecalis can develop resistance to linezolid in environments with excessive linezolid use. The aim of this study was to define risk factors and outcome associated with the acquisition of linezolid-resistant E. faecalis (LREfs). Methods: A retrospective case–control study was designed including patients hospitalised from January 2014 to October 2017 at Hospital Civil de Guadalajara ‘Fray Antonio Alcalde’ in Guadalajara, Mexico. A total of 50 patients culture-positive for LREfs and 100 control patients hospitalised in the same room and time as the cases were included. Clinical and demographic data were collected and analysed. Results: Risk factors for the presence of LREfs included prior linezolid use [odds ratio (OR) = 6.74], prior clindamycin use (OR = 6.72) and previous surgery (OR = 5.79). The mortality rate was 18% for LREfs cases versus 9% for controls. Conclusion: LREfs has emerged and spread in our hospital, an environment in which linezolid use is considerable. Risk factors for LREfs are prior antibiotic use, including linezolid, and previous surgery

Clostridium difficile outbreak caused by NAP1/BI/027 strain and non-027 strains in a Mexican hospital

Background: Clostridium difficile infections caused by the NAP1/B1/027 strain are more severe, difficult to treat, and frequently associated with relapses. Methods: A case–control study was designed to examine a C. difficile infection (CDI) outbreak over a 12-month period in a Mexican hospital. The diagnosis of toxigenic CDI was confirmed by real-time polymerase chain reaction, PCR (Cepheid Xpert C. difficile/Epi). Results: During the study period, 288 adult patients were evaluated and 79 (27.4%) patients had confirmed CDI (PCR positive). C. difficile strain NAP1/B1/027 was identified in 31 (39%) of the patients with confirmed CDI (240 controls were included). Significant risk factors for CDI included any underlying disease (p < 0.001), prior hospitalization (p < 0.001), and antibiotic (p < 0.050) or steroid (p < 0.001) use. Laboratory abnormalities included leukocytosis (p < 0.001) and low serum albumin levels (p < 0.002). Attributable mortality was 5%. Relapses occurred in 10% of patients. Risk factors for C. difficile NAP1/B1/027 strain infections included prior use of quinolones (p < 0.03). Risk factors for CDI caused by non-027 strains included chronic cardiac disease (p < 0.05), chronic renal disease (p < 0.009), and elevated serum creatinine levels (p < 0.003). Deaths and relapses were most frequent in the 027 group (10% and 19%, respectively). Conclusions: C. difficile NAP1/BI/027 strain and non-027 strains are established pathogens in our hospital. Accordingly, surveillance of C. difficile infections is now part of our nosocomial prevention program

Genetic Diversity of Mycobacterium tuberculosis from Guadalajara, Mexico and Identification of a Rare Multidrug Resistant Beijing Genotype

Determining the genetic diversity of M. tuberculosis strains allows identification of the distinct Mycobacterium tuberculosis genotypes responsible for tuberculosis in different regions. Several studies have reported the genetic diversity of M. tuberculosis strains in Mexico, but little information is available from the state of Jalisco. Therefore, the aim of this study was to determine the genetic diversity of Mycobacterium tuberculosis clinical isolates from Western Mexico. Sixty-eight M. tuberculosis isolates were tested for susceptibility to first-line drugs using manual Mycobacteria Growth Indicator Tube method and genotyped using spoligotyping and IS6110-restriction fragment length polymorphism (RFLP) pattern analyses. Forty-seven (69.1%) isolates were grouped into 10 clusters and 21 isolates displayed single patterns by spoligotyping. Three of the 21 single patterns corresponded to orphan patterns in the SITVITWEB database, and 1 new type that contained 2 isolates was created. The most prevalent lineages were T (38.2%), Haarlem (17.7%), LAM (17.7%), X (7.4%), S (5.9%), EAI (1.5%) and Beijing (1.5%). Six (12.8%) of the clustered isolates were MDR, and type 406 of the Beijing family was among the MDR isolates. Seventeen (26.2%) isolates were grouped into 8 clusters and 48 isolates displayed single patterns by IS6110-RFLP. Combination of IS6110-RFLP and spoligotyping reduced the clustering rate to 20.0%. The results show that T, Haarlem, and LAM are predominant lineages among clinical isolates of M. tuberculosis in Guadalajara, Mexico. Clustering rates indicated low transmission of MDR strains. We detected a rare Beijing genotype, SIT406, which was a highly resistant strain. This is the first report of this Beijing genotype in Latin America

Clinical characteristics associated with the severity of Clostridium [Clostridioides] difficile infection in a tertiary teaching hospital from Mexico

Background: Clostridium difficile infection (CDI) is a leading cause of healthcare-associated diarrhea worldwide. In this study, risk factors associated with the development of severe-complicated and recurrent outcomes in CDI patients in different age groups, including the non-elderly, were assessed in a third-level hospital. Methods: CDI cases were detected by clinical data and polymerase-chain-reaction (PCR). Clinical, demographic, epidemiological, and microbiological risk factors for CDI were evaluated. Results: During the study period, 248 out of 805 patients with nosocomial diarrhea were diagnosed with CDI and the majority were severe-complicated cases (87.90%). Female gender (OR 3.19, 95% CI 1.19e8.55, p ¼ 0.02) and lymphoma (OR 3.95, 95% CI 1.03e15.13, p ¼ 0.04) were risk factors for severe-complicated CDI. Mature adulthood (51e60 years) (OR 5.80, 95% CI 1.56e21.62, p ¼ 0.01), previous rifampicin use (OR 7.44, 95% CI 2.10e26.44, p ¼ 0.00), and neoplasm (solid malignant neoplasm or hematological malignancies) (OR 4.12, 95% CI 1.01e16.83, p ¼ 0.04) were risk factors for recurrent infection. Autoimmune disorders (OR 6.62, CI 95% 1.26e34.73, p ¼ 0.02), leukemia (OR 4.97, 95% CI 1.05e23.58, p ¼ 0.04), lymphoma (OR 3.79, 95% CI 1.03e12.07, p ¼ 0.04) and previous colistin treatment (OR 4.97, 95% CI 1.05e23.58, p ¼ 0.04) were risk factors for 30-day mortality. Conclusion: Newly identified risk factors for recurrent CDI were rifampicin treatment and age between 51 and 60 years; colistin treatment was identified as a risk factor for 30-day mortality. Previously identified risk factors for severe-complicated CDI were confirmed, but with a major impact on non-elderly patients

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Multi-ancestry genome-wide association study of asthma exacerbations

Altres ajuts: European Regional Development Fund "ERDF A way of making Europe"; Allergopharma-EAACI award 2021; SysPharmPedia grant from the ERACoSysMed 1st Joint Transnational Call from the European Union under the Horizon 2020; Sandler Family Foundation; American Asthma Foundation; RWJF Amos Medical Faculty Development Program; National Heart, Lung, and Blood Institute of the National Institutes of Health (R01HL117004, R01HL128439, R01HL135156, X01HL134589, R01HL141992, R01HL141845); National Institute of Health and Environmental Health Sciences (R01ES015794, R21ES24844); National Institute on Minority Health and Health Disparities (NIMHD) (P60MD006902, R01MD010443, R56MD013312); National Institute of General Medical Sciences (NIGMS) (RL5GM118984); Tobacco-Related Disease Research Program (24RT-0025, 27IR-0030); National Human Genome Research Institute (NHGRI) (U01HG009080); GlaxoSmithKline and Utrecht Institute for Pharmaceutical Sciences; Slovenian Research Agency (P3-0067); SysPharmPediA grant, co-financed by the Ministry of Education, Science and Sport Slovenia (MIZS) (C3330-16-500106); NHS Research Scotland; Wellcome Trust Biomedical Resource (099177/Z/12/Z); Genotyping National Centre (CeGEN) CeGen-PRB3-ISCIII (AC15/00015); UK Medical Research Council and Wellcome (102215/2/13/2); University of Bristol; Swedish Heart-Lung Foundation, Swedish Research Council; Region Stockholm (ALF project and database maintenance); NHS Chair of Pharmacogenetics via the UK Department of Health; Innovative Medicines Initiative (IMI) (115010); European Federation of Pharmaceutical Industries and Associations (EFPIA); Spanish National Cancer Research Centre; Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC19/17); Erasmus Medical Center; Erasmus University Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF); U.S. National Institutes of Health (HL07966); European Social Fund "ESF Investing in your future"; Ministerio de Ciencia, Innovación y Universidades; Universidad de La Laguna (ULL); European Academy of Allergy and Clinical Immunology (EAACI); European Respiratory Society (ERS) (LTRF202101-00861); Ministry of Education, Science and Sport of the Republic of Slovenia (C3330-19-252012); Singapore Ministry of Education Academic Research Fund; Singapore Immunology Network (SIgN); National Medical Research Council (NMRC Singapore); Biomedical Research Council (BMRC Singapore); Agency for Science Technology and Research (A*STAR Singapore, N-154-000-038-001, R-154-000-191-112, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, R-154-000-A91-592, R-154-000-A95-592, R-154-000-B99-114, BMRC/01/1/21/18/077, BMRC/04/1/21/19/315, SIgN-06-006, SIgN-08-020, NMRC/1150/2008, H17/01/a0/008); Sime Darby Technology Centre; First Resources Ltd; Genting Plantation; Olam International; U.S. National Institutes of Health (HL138098).Background: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. Methods: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. Results: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (OR) = 0.82, p = 9.05 × 10 and replication: OR = 0.89, p = 5.35 × 10) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: OR = 0.85, p = 3.10 × 10 and replication: OR = 0.89, p = 1.30 × 10). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. Conclusions: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense

Forest Biomass Density across Large Climate Gradients in Northern South America is related to Water Availability but not with Temperature

Understanding and predicting the likely response of ecosystems to climate change are crucial challenges for ecology and for conservation biology. Nowhere is this challenge greater than in the tropics as these forests store more than half the total atmospheric carbon stock in their biomass. Biomass is determined by the balance between biomass inputs (i.e., growth) and outputs (mortality). We can expect therefore that conditions that favor high growth rates, such as abundant water supply, warmth, and nutrient-rich soils will tend to correlate with high biomass stocks. Our main objective is to describe the patterns of above ground biomass (AGB) stocks across major tropical forests across climatic gradients in Northwestern South America. We gathered data from 200 plots across the region, at elevations ranging between 0 to 3400 m. We estimated AGB based on allometric equations and values for stem density, basal area, and wood density weighted by basal area at the plot-level. We used two groups of climatic variables, namely mean annual temperature and actual evapotranspiration as surrogates of environmental energy, and annual precipitation, precipitation seasonality, and water availability as surrogates of water availability. We found that AGB is more closely related to water availability variables than to energy variables. In northwest South America, water availability influences carbon stocks principally by determining stand structure, i.e. basal area. When water deficits increase in tropical forests we can expect negative impact on biomass and hence carbon storage