Trends of Bloodstream Infections in a University Hospital During 12 Years

This study aims to investigate trends in bloodstream infections and their antimicrobial susceptibility profiles over 12 years in our hospital. This retrospective study was carried out in the Bursa Uludag University Hospital, Turkey, during 2008–2019. Blood cultures from patients were performed using BACTEC System. Isolates were identified with Phoenix System until 2018 and “matrix-assisted laser desorption ionization time-of-flight mass spectrometry” (MALDI-TOF MS) in 2019. Antibiotic susceptibility testing was performed with Phoenix System. Patient data came from the BD EpiCenter™ data management system. Escherichia coli was found to be the most common Gram-negative (11.6%), and coagulase-negative staphylococci were the most common Gram-positive (10.1%) monomicrobial growth. Overall, there was a significant increase in rates of extended-spectrum β-lactamase positive E. coli (p = 0.014) and Klebsiella pneumonia (p < 0.001), carbapenem-resistant E. coli (p < 0.001), and K. pneumoniae (p < 0.001) and colistin-resistant K. pneumoniae (p < 0.001) and Acinetobacter baumannii (p < 0.001) over 12 years. Carbapenem and colistin resistance has increased dramatically in recent years. We believe that regular monitoring of the distribution of pathogens and antibiotic susceptibility profiles, especially in intensive care units, can contribute to evidence for the increase in resistant microorganisms and help prevent their spread with antimicrobial stewardship and infection control policies.     

Etiologic Agents of Central Nervous System Infections among Febrile Hospitalized Patients in the Country of Georgia

Objectives

There is a large spectrum of viral, bacterial, fungal, and prion pathogens that cause central nervous system (CNS) infections. As such, identification of the etiological agent requires multiple laboratory tests and accurate diagnosis requires clinical and epidemiological information. This hospital-based study aimed to determine the main causes of acute meningitis and encephalitis and enhance laboratory capacity for CNS infection diagnosis.

Methods

Children and adults patients clinically diagnosed with meningitis or encephalitis were enrolled at four reference health centers. Cerebrospinal fluid (CSF) was collected for bacterial culture, and in-house and multiplex RT-PCR testing was conducted for herpes simplex virus (HSV) types 1 and 2, mumps virus, enterovirus, varicella zoster virus (VZV), Streptococcus pneumoniae, HiB and Neisseria meningitidis.

Results

Out of 140 enrolled patients, the mean age was 23.9 years, and 58% were children. Bacterial or viral etiologies were determined in 51% of patients. Five Streptococcus pneumoniae cultures were isolated from CSF. Based on in-house PCR analysis, 25 patients were positive for S. pneumoniae, 6 for N. meningitidis, and 1 for H. influenzae. Viral multiplex PCR identified infections with enterovirus (n = 26), VZV (n = 4), and HSV-1 (n = 2). No patient was positive for mumps or HSV-2.

Conclusions

Study findings indicate that S. pneumoniae and enteroviruses are the main etiologies in this patient cohort. The utility of molecular diagnostics for pathogen identification combined with the knowledge provided by the investigation may improve health outcomes of CNS infection cases in Georgia.     

Astrocyte-Derived CXCL10 Drives Accumulation of Antibody-Secreting Cells in the Central Nervous System during Viral Encephalomyelitis

Microbial infections of the central nervous system (CNS) are often associated with local accumulation of antibody (Ab)-secreting cells (ASC). By providing a source of Ab at the site of infection, CNS-localized ASC play a critical role in acute viral control and in preventing viral recrudescence. Following coronavirus-induced encephalomyelitis, the CNS accumulation of ASC is chemokine (C-X-C motif) receptor 3 (CXCR3) dependent. This study demonstrates that CNS-expressed CXCR3 ligand CXCL10 is the critical chemokine regulating ASC accumulation. Impaired ASC recruitment in CXCL10^−/− but not CXCL9^−/− mice was consistent with reduced CNS IgG and κ-light chain mRNA and virus-specific Ab. Moreover, the few ASC recruited to the CNS in CXCL10^−/− mice were confined to the vasculature, distinct from the parenchymal localization in wild-type and CXCL9^−/− mice. However, neither CXCL9 nor CXCL10 deficiency diminished neutralizing serum Ab, supporting a direct role for CXCL10 in ASC migration. T cell accumulation, localization, and effector functions were also not affected in either CXCL9^−/− or CXCL10^−/− mice, consistent with similar control of infectious virus. There was also no evidence for dysregulation of chemokines or cytokines involved in ASC regulation. The distinct roles of CXCL9 and CXCL10 in ASC accumulation rather coincided with their differential localization. While CXCL10 was predominantly expressed by astrocytes, CXCL9 expression was confined to the vasculature/perivascular spaces. These results suggest that CXCL10 is critical for two phases: recruitment of ASC to the CNS vasculature and ASC entry into the CNS parenchyma.     

Evaluation of mRNA Biomarkers to Identify Risk of Hospital Acquired Infections in Children Admitted to Paediatric Intensive Care Unit

Objectives

Hospital-acquired infections (HAI) are associated with significant mortality and morbidity and prolongation of hospital stay, adding strain on limited hospital resources. Despite stringent infection control practices some children remain at high risk of developing HAI. The development of biomarkers which could identify these patients would be useful. In this study our objective was to evaluate mRNA candidate biomarkers for HAI prediction in a pediatric intensive care unit.

Design

Serial blood samples were collected from patients admitted to pediatric intensive care unit between March and June 2012. Candidate gene expression (IL1B, TNF, IL10, CD3D, BCL2, BID) was quantified using RT-qPCR. Comparisons of relative gene expression between those that did not develop HAI versus those that did were performed using Mann Whitney U-test.

Patients

Exclusion criteria were: age <28 days or ≥16 years, expected length of stay < 24 hours, expected survival < 28 days, end-stage renal disease and end-stage liver disease. Finally, 45 children were included in this study.

Main Results

The overall HAI rate was 30% of which 62% were respiratory infections. Children who developed HAI had a three-fold increase in hospital stay compared to those who did not (27 days versus 9 days, p<0.001). An increased expression of cytokine genes (IL1B and IL10) was observed in patients who developed HAI, as well as a pro-apoptosis pattern (higher expression of BID and lower expression of BCL2). CD3D, a key TCR co-factor was also significantly down-modulated in patients who developed HAI.

Conclusions

To our knowledge, this is the first study of mRNA biomarkers of HAI in the paediatric population. Increased mRNA expressions of anti-inflammatory cytokine and modulation of apoptotic genes suggest the development of immunosuppression in critically ill children. Immune monitoring using a panel of genes may offer a novel stratification tool to identify HAI risk.     

Premature Termination of MexR Leads to Overexpression of MexAB-OprM Efflux Pump in Pseudomonas aeruginosa in a Tertiary Referral Hospital in India

ObjectivesThe present study was undertaken to investigate the mutations that are present in mexR gene of multidrug resistant (MDR) isolates of Pseudomonas aeruginosa collected from a tertiary referral hospital of north east India.Methods76 MDR clinical isolates of P. aeruginosa were obtained from the patients who were admitted to or attended the clinics of Silchar medical college and hospital. They were screened phenotypically for the presence of efflux pump activity by an inhibitor based method. Acquired resistance mechanisms were detected by multiplex PCR. Real time PCR was performed to study the expression of mexA gene of MexAB-OprM efflux pump in isolates with increase efflux pump activity. mexR gene of the isolates with overexpressed MexAB-OprM efflux pump was amplified, sequenced and analysed.ResultsOut of 76 MDR isolates, 24 were found to exhibit efflux pump activity phenotypically against ciprofloxacin and meropenem. Acquired resistance mechanisms were absent in 11 of them and among those isolates, 8 of them overexpressed MexAB-OprM. All the 8 isolates possessed mutation in mexR gene. 11 transversions, 4 transitions, 2 deletion mutations and 2 insertion mutations were found in all the isolates. However, the most significant observation was the formation of a termination codon at 35^th position which resulted in the termination of the polypeptide and leads to overexpression of the MexAB-OprM efflux pump.ConclusionsThis study highlighted emergence of a novel mutation which is probably associated with multi drug resistance. Therefore, further investigations and actions are needed to prevent or at least hold back the expansion and emergence of newer mutations in nosocomial pathogens which may compromise future treatment options.     

Outcomes and Costs of Poisoned Patients Admitted to an Adult Emergency Department of a Spanish Tertiary Hospital: Evaluation through a Toxicovigilance Program

AbstractToxicovigilance is the active process of identifying and evaluating the toxic risks existing in a community, and evaluating the measures taken to reduce or eliminate them.ObjectiveThrough a validated toxicovigilance program (SAT-HULP) we examined the characteristics of acute poisoning cases (APC) attended in the Emergency Department (ED) of La Paz Hospital (Madrid, Spain) and assessed their economic impact on the health system.ResultsDuring the first 30 month of SAT-HULP operation we found a total of 3,195 APC, a cumulative incidence rate of 1.75% of patients attended in the ED. The mean (SD) patient age was 40.9 (17.8) years and 51.2% were men. Drug abuse accounted for 47.5% of the cases. Suicide attempt was the second most frequent category (38.1%) and other causes accounted for 14.5% of APC. The total cost of hospital care for our hospital rose to €1,825,263.24 (approximately €730,105.30/year) resulting in a permanent occupation of 4 beds/year.ConclusionsSAT-HULP constitutes a validated toxicovigilance tool, which continuously integrates available data in real-time and helps health services manage APC data flexibly, including the consumption of resources from the health system.     

Cellular Inflammatory Response to Flaviviruses in the Central Nervous System of a Primate Host

Flaviviruses such as tick-borne encephalitis virus, Japanese encephalitis virus, West Nile virus, and St. Louis encephalitis virus are important neurotropic human pathogens, typically causing a devastating and often fatal neuroinfection. Flaviviruses induce neuroinflammation with typical features of viral encephalitides, including inflammatory cell infiltration, activation of microglia, and neuronal degeneration. Development of safe and effective live-virus vaccines against neurotropic flavivirus infections demands a detailed knowledge of their neuropathogenesis in a primate host that is evolutionarily close to humans. Here, we used computerized morphometric analysis to quantitatively assess the cellular inflammatory responses in the central nervous system (CNS) of rhesus monkeys infected with three antigenically divergent attenuated flaviviruses. The kinetics, spatial pattern, and magnitude of microglial activation, trafficking of T and B cells, and changes in T cell subsets within the CNS define unique phenotypic signatures for each of the three viruses. Our results provide a benchmark for investigation of cellular inflammatory responses induced by attenuated flaviviruses in the CNS of primate hosts and provide insight into the neuropathogenesis of flavivirus encephalitis that might guide the development of safe and effective live-virus vaccines. (J Histochem Cytochem 57:973–989, 2009)     

Differential Influence of Interleukin-12 in the Pathogenesis of Autoimmune and Virus-Induced Central Nervous System Demyelination

Experimental allergic encephalomyelitis (EAE) and Theiler’s murine encephalomyelitis virus (TMEV) disease are two demyelinating diseases of the central nervous system (CNS) that serve as animal models for multiple sclerosis. Th1 cells are thought to play a role in the pathogenesis of CNS demyelination in both these diseases. We show here the differential influence of interleukin 12, a critical cytokine for the development of Th1 cells in EAE and TMEV disease.     

High Numbers of Viral RNA Copies in the Central Nervous System of Mice during Persistent Infection with Theiler's Virus

The low-neurovirulence Theiler's murine encephalomyelitis viruses (TMEV), such as BeAn virus, cause a persistent infection of the central nervous system (CNS) in susceptible mouse strains that results in inflammatory demyelination. The ability of TMEV to persist in the mouse CNS has traditionally been demonstrated by recovering infectious virus from the spinal cord. Results of infectivity assays led to the notion that TMEV persists at low levels. In the present study, we analyzed the copy number of TMEV genomes, plus- to minus-strand ratios, and full-length species in the spinal cords of infected mice and infected tissue culture cells by using Northern hybridization. Considering the low levels of infectious virus in the spinal cord, a surprisingly large number of viral genomes (mean of 3.0 x 10(9)) was detected in persistently infected mice. In the transition from the acute (approximately postinfection [p.i.] day 7) to the persistent (beginning on p.i. day 28) phase of infection, viral RNA copy numbers steadily increased, indicating that TMEV persistence involves active viral RNA replication. Further, BeAn viral genomes were full-length in size; i.e., no subgenomic species were detected and the ratio of BeAn virus plus- to minus-strand RNA indicated that viral RNA replication is unperturbed in the mouse spinal cord. Analysis of cultured macrophages and oligodendrocytes suggests that either of these cell types can potentially synthesize high numbers of viral RNA copies if infected in the spinal cord and therefore account for the heavy viral load. A scheme is presented for the direct isolation of both cell types directly from infected spinal cords for further viral analyses.     

Accessibility of Galactosyl Ceramides to Probe Reagents in Central Nervous System Myelin

The suitability of isolated central nerve myelin preparations for probe labelling studies was assessed and the accessibility of galactosyl ceramides in myelin to galactose oxidase and sodium periodate was determined. Isolated myelin preparations present a uniform external membrane surface to added probes because lamellae in the myelin sheath separate at their external apposition surfaces exclusively during isolation. The cytoplasmic apposition remains intact in isolated myelin. Cationised ferritin can gain access along external apposition regions of inner lamellae in multilamellar fragments of isolated myelin, indicating that proteins and lipids on the external membrane surface will be accessible to probes. Over 50% of the total galactosyl ceramides of myelin are accessible to galactose oxidase attack; hydroxy fatty acid- and nonhydroxy fatty acid-containing cerebrosides are equally attacked. Sodium periodate attacks over 90% of the galactosyl ceramides in isolated myelin at 20°C and electron micrographs of the periodate-treated myelin reveal changes at the external apposition only. Galactosyl ceramides in vesicles of myelin lipid vesicles are not so readily attacked by periodate. The disposition of galactosyl ceramides in the myelin lamellae is discussed.     

Structure and Location of a Gabaa Receptor Complex in the Central Nervous System

Abstract

GABA-gated chloride channels in the central nervous system contain a regulatory site, the benzodiazepine receptor, through which drugs can modulate the efficiency of GABAergic synaptic transmission and thereby affect the degree of anxiety, muscle tension, vigilance and convulsions. The biochemical analysis of the purified receptor complex with monoclonal antibodies shows a heterooligomeric composition of two glycosylated subunits (α,β). The immunoprecipitated complex contains the binding sites for GABA, benzodiazepines and the convulsant TBPS. The receptor complex was located, immuno-cytochemically, in synapses of brain regions rich in GABAergic nerve terminals.     

Toll信号通路在中枢神经系统损伤中的作用

Toll样受体(Toll-like receptors,TLR)是先天性免疫反应识别病原体的一个重要分子,在免疫系统中发挥关键作用.其家族各种成员的主要功能是识别入侵病原体表面的各种不同分子模式,随后启动免疫反应,达到保护机体作用.在大脑中,小胶质细胞可以作为抗原提呈细胞,参与脑内免疫反应,也可以通过分泌各种促炎症因子启动或促进免疫反应,而TLR家族在中枢神经免疫系统的作用仍存在争议,它既可以通过促进神经免疫反应枢纽因子的表达来增强免疫,也可因免疫过度而损伤神经细胞.总之,Toll信号通路对中枢神经系统疾病有一定的调控作用.     

Prevalence of Oral and Maxillofacial Trauma in Elders Admitted to a Reference Hospital in Northeastern Brazil

Objective

To know the prevalence and etiology of oral and maxillofacial trauma in elders.

Methods

Analytical quantitative cross-sectional study conducted at a public trauma hospital located in Fortaleza-Ceará, Brazil. The study population comprised patients with trauma who were hospitalized from April to August 2014. Of these patients, patients with oral and maxillofacial trauma were chosen to be included in the research. A questionnaire was administered in order to obtain information on socio-demographics, systemic comorbidities, use of medication, deleterious habits (smoking and alcohol consumption), etiology of oral and maxillofacial trauma and type of pre-hospital care.

Results

Of the 280 elderly hospitalized with trauma, 47 had oral and maxillofacial trauma, with a prevalence of 16.8%. In this group, the age ranged from 60 to 88 years, with a mean age of 72.4 years (SD± 8.38). The elderly were mostly women (55.3%), self-declared pardos (53.2%), who presented with cardiovascular disorders (48.9%), and who received formal pre-hospital care (70.2%). Elderly who were in the 60–69 years age group, spent 6–9 years at school and drank alcohol were 2.64, 3.75, and 1.97, respectively, more likely to suffer oral and maxillofacial trauma. The main causes of trauma were physical aggression, traffic accidents, falls and domestic accidents. All of the physical aggressions resulted in oral and maxillofacial traumas, and the elderly who suffered traffic accidents were four times more likely to have oral and maxillofacial trauma.

Conclusion

The prevalence of 16.8% and the lack of research on oral and maxillofacial traumas in the elderly is worrisome and should be included in the oral health indicators for the elderly population to support the importance of oral health.