Synergistic activity between colistin and the ionic liquids 1-methyl-3-dodecylimidazolium bromide, 1-dodecyl-1-methylpyrrolidinium bromide, or 1-dodecyl-1-methylpiperidinium bromide against Gram-negative bacteria

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Diagnosis of bloodstream infections by mass spectrometry : present and future

Rapid identification and antimicrobial susceptibility testing of the causative agent(s) of bloodstream infections may impact on the clinical outcome of patients, which is directly related to the prompt administration of an effective antimicrobial therapy. Empirical antimicrobial therapy is chosen on the basis of clinical and epidemiological data and it is administered immediately after blood sampling but, in a significant number of cases, it has to be streamlined on the basis of the microbiological report. Rapid identification has a clinically relevant impact on the timely selection of an appropriate antimicrobial therapy, especially in low-prevalence areas for antimicrobial resistance. Recently, the identification process of isolated bacteria has been revolutionized by the introduction of mass spectrometry (MS), particularly MALDI-TOF, in clinical microbiology laboratories. Furthermore, MALDI-TOF is one of the most promising techniques for the identification of bacterial and fungal infectious agents directly from positive blood cultures and a potentially useful tool for the detection of antimicrobial resistance, specifically that conferred by -lactamases. Although blood culture remains, at present, the gold standard to diagnose bloodstream infections, newly developed MALDI-TOF methods are useful adjunctive tests to fasten the diagnostic process and further increase the diagnostic yield

A new rapid method for direct antimicrobial susceptibility testing of bacteria from positive blood cultures

Background: Rapid identification and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections can lead to prompt appropriate antimicrobial therapy. To shorten species identification, in this study bacteria were recovered from monomicrobial blood cultures by serum separator tubes and spotted onto the target plate for direct MALDI-TOF MS identification. Proper antibiotics were selected for direct AST based on species identification. In order to obtain rapid AST results, bacteria were recovered from positive blood cultures by two different protocols: by serum separator tubes (further referred to as PR1), or after a short-term subculture in liquid medium (further referred to as PR2). The results were compared with those obtained by the method currently used in our laboratory consisting in identification by MALDI-TOF and AST by Vitek 2 or Sensititre on isolated colonies. Results: The direct MALDI-TOF method concordantly identified with the current method 97.5 % of the Gram-negative bacteria and 96.1 % of the Gram-positive cocci contained in monomicrobial blood cultures. The direct AST by PR1 and PR2 for all isolate/antimicrobial agent combinations was concordant/correct with the current method for 87.8 and 90.5 % of Gram-negative bacteria and for 93.1 and 93.8 % of Gram-positive cocci, respectively. In particular, 100 % categorical agreement was found with levofloxacin for Enterobacteriaceae by both PR1 and PR2, and 99.0 and 100 % categorical agreement was observed with linezolid for Gram-positive cocci by PR1 and PR2, respectively. There was no significant difference in accuracy between PR1 and PR2 for Gram-negative bacteria and Gram-positive cocci. Conclusions: This newly described method seems promising for providing accurate AST results. Most importantly, these results would be available in a few hours from blood culture positivity, which would help clinicians to promptly confirm or streamline an effective antibiotic therapy in patients with bloodstream infections

In vitro bactericidal activity of human beta-defensin 3 against multidrug-resistant nosocomial strains

The antimicrobial activity of human beta-defensin 3 (hBD-3) against multidrug-resistant clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Acinetobacter baumannii was evaluated. A fast bactericidal effect (within 20 min) against all bacterial strains tested was observed. The presence of 20% human serum abolished the bactericidal activity of hBD-3 against gram-negative strains and reduced the activity of the peptide against gram-positive strains

Involvement of the<i>Mycobacterium tuberculosis</i>secreted antigen SA-5K in intracellular survival of recombinant<i>Mycobacterium smegmatis</i>

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Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes

Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project

This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21–30, 31–40, 41–50, 51–60, 61–70, and 71–80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes

Pulse wave velocity as marker of preclinical arterial disease: reference levels in a uruguayan population considering wave detection algorithms, path lengths, aging, and blood pressure

Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the &quot;reference population&quot;; the group of subjects with optimal/normal blood pressures levels at study time represented the &quot;normal population.&quot; Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe