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Perez-Lago L.,Hospital Gregorio Maranon | Perez-Lago L.,Institute Investigacion Biomedica Gregorio Maranon | Herranz M.,Hospital Gregorio Maranon | Herranz M.,Institute Investigacion Biomedica Gregorio Maranon | And 8 more authors.
Journal of Clinical Microbiology | Year: 2011

Under certain circumstances, it is possible to identify clonal variants of Mycobacterium tuberculosis infecting a single patient, probably as a result of subtle genetic rearrangements in part of the bacillary population. We systematically searched for these microevolution events in a different context, namely, recent transmission chains. We studied the clustered cases identified using a population-based universal molecular epidemiology strategy over a 5-year period. Clonal variants of the reference strain defining the cluster were found in 9 (12%) of the 74 clusters identified after the genotyping of 612 M. tuberculosis isolates by IS6110 restriction fragment length polymorphism analysis and mycobacterial interspersed repetitive units-variable-number tandem repeat typing. Clusters with microevolution events were epidemiologically supported and involved 4 to 9 cases diagnosed over a 1- to 5-year period. The IS6110 insertion sites from 16 representative isolates of reference and microevolved variants were mapped by ligation-mediated PCR in order to characterize the genetic background involved in microevolution. Both intragenic and intergenic IS6110 locations resulted from these microevolution events. Among those cases of IS6110 locations in intergenic regions which could have an effect on the regulation of adjacent genes, we identified the overexpression of cytochrome P450 in one microevolved variant using quantitative real-time reverse transcription-PCR. Our results help to define the frequency with which microevolution can be expected in M. tuberculosis transmission chains. They provide a snapshot of the genetic background of these subtle rearrangements and identify an event in which IS6110-mediated microevolution in an isogenic background has functional consequences. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Roa P.L.,Hospital General Universitario Gregorio Maranon | Roa P.L.,Institute Investigacion Biomedica Gregorio Maranon | Perez-Granda M.J.,Institute Investigacion Biomedica Gregorio Maranon | Perez-Granda M.J.,Complutense University of Madrid | And 12 more authors.
PLoS ONE | Year: 2015

Background Reactivation of cytomegalovirus (CMV) has been reported occasionally in immnunocompetent patients in the intensive care unit (ICU). The epidemiology and association of CMV infection with adverse outcome is not well defined in this population. Patients undergoing major heart surgery (MHS) are at a particularly high risk of infection. CMV infection has not been systematically monitored in MSH-ICU patients. Methods We assessed CMV plasma viremia weekly using a quantitative polymerase chain reaction assay in a prospective cohort of immunocompetent adults admitted to the MHS-ICU for at least 72 hours between October 2012 and May 2013. Risk factors for CMV infection and its potential association with continued hospitalization or death by day 30 (composited endpoint) were assessed using univariate and multivariate logistic regression analyses. Results CMV viremia at any level was recorded in 16.5% of patients at a median of 17 days (range, 3-54 days) after admission to the MHS-ICU. Diabetes (adjusted OR, 5.6; 95% CI, 1.8-17.4; p=0.003) and transfusion requirement (>10 units) (adjusted OR, 13.7; 95% CI, 3.9-47.8; p.<0.001) were independent risk factors associated with CMV reactivation. Reactivation of CMV at any level was independently associated with the composite endpoint (adjusted OR, 12.1; 95% CI, 2.3-64; p=0.003). Conclusion Reactivation of CMV is relatively frequent in immunocompetent patients undergoing MHS and is associated with prolonged hospitalization or death. © 2015 Roa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Perez-Granda M.J.,Complutense University of Madrid | Perez-Granda M.J.,Institute Investigacion Biomedica Gregorio Maranon | Perez-Granda M.J.,CIBER ISCIII | Barrio J.,Complutense University of Madrid | And 16 more authors.
PLoS ONE | Year: 2014

Background: Lock-therapy with antimicrobials has been used for the treatment and prevention of catheter-related bloodstream infections (CR-BSI). Experiences with Ethanol-Locks (E-locks) have included therapeutic interventions with variable results. Patients undergoing Major Heart Surgery (MHS) are a high-risk population for CR-BSI.The aim of this study was to assess the efficacy and tolerance to E-Locks in the prevention of CR-BSI of patients undergoing MHS. Methods and Findings: This is an academic, prospective, randomized, non-blinded and controlled clinical trial assessing the incidence of CR-BSI of patients with E-locks (E-lock) and the tolerance to the procedure in comparison with patients receiving conventional catheter-care (CCC). Patients undergoing MHS with intravascular catheters for more than 48 hours were randomly assigned into treatment or control group by a computer-generated list of randomly assigned numbers. In the treatment group, all their catheter lumens were locked with an ethanol solution at 70% for two hours, every three days (E-Locks). The control group received conventional catheter-care (CCC). Overall, 200 patients with 323 catheters were included in the study, which was stopped after 10 months due to adverse events. Of them, 179 catheters (113 patients) had E-Locks and 144 catheters (87 patients) were CCC. Euroscore Surgical Risk in both groups was 4.04 vs 4.07 p = 0.94 respectively. The results for the E-Locks and CCC were as follows: Incidence of CR-BSI/1000 days of exposure 2.1 vs 5.2 (p = 0.33), catheter tip colonization 14 (7.8%) vs 6 (4.2%) patients (p = 0.17), median length of hospital stay, 15 vs 16 days (p = 0.77). Seven patients (6.19%), all in the ethanol branch, had to discontinue the trial due to intolerance or adverse events. Conclusions: We do not recommend prophylaxis of CR-BSI with ethanol-lock on a routine basis in patients undergoing Major Heart Surgery. Trial Registration: Clinical Trials.gov NCT01229592. © 2014 P Pérez-Granda et al.

Perez-Garcia F.,Hospital General Universitario Gregorio Maranon | Vasquez V.,Hospital General Universitario Gregorio Maranon | de Egea V.,Hospital General Universitario Gregorio Maranon | de Egea V.,Institute Investigacion Biomedica Gregorio Maranon | And 7 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2016

Influenza virus infection remains a major cause of morbidity and mortality during winter seasons. Bacterial and virus co-infection is a commonly described situation in these patients. However, data on co-infection by influenza A and B viruses are lacking. In this study, we present the cases of co-infection by influenza A and B viruses during the winter season of 2014–2015 in our institution. We analyzed 2759 samples from 2111 patients and found that 625 samples corresponding to 609 patients were positive for influenza A or B virus. A total of 371 patients had influenza A, 228 had influenza B, and 10 (1.6 %) had influenza A and B virus detection in the same sample. The median age of co-infected patients was 78.6 years, and only one of the co-infected patients died because of the infection. Comparison with a control group of mono-infected patients revealed that co-infection was significantly associated with nosocomial acquisition [odds ratio (OR) = 4.5, 95 % confidence interval (CI) = 1.05–19.25, p = 0.042]. However, co-infection was not associated with worse outcome, previous underlying condition, or vaccination status. Multivariate analysis revealed that co-infection was not an independent risk factor for death and that no single risk factor could predict co-infection. © 2016, Springer-Verlag Berlin Heidelberg.

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