Project description:Here we have performed targeted quantitative N-glycoproteomics from plasma samples of patients with confirmed positive blood culture together with age and sex matched febrile controls with negative blood culture reports. Three hundred and sixty eight potential N-glycopeptides were quantified by mass spectrometry and 149 were further selected for identification. Twenty four N-glycopeptides were identified with high confidence together with elucidation of the peptide sequence, N-glycosylation site, glycan composition and proposed glycan structures. these N-glycopeptides can be used as potential biomarkers of bloodstream infection.
Project description:BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile infections declined across the UK National Health Service in the decade that followed implementation of an infection control campaign. The national impact on intensive care unit (ICU)-acquired infections has not been documented.MethodsData on MRSA, C. difficile, vancomycin-resistant Enterococcus (VRE), and ICU-acquired bloodstream infections (UABSIs) for 1 189 142 patients from 2007 to 2016 were analyzed. Initial coverage was 139 ICUs increasing to 276 ICUs, representing 100% of general adult UK ICUs.ResultsICU MRSA and C. difficile acquisitions per 1000 patients decreased between 2007 and 2016 (MRSA acquisitions, 25.4 to 4.1; and C. difficile acquisitions, 11.1 to 3.5), whereas VRE acquisitions increased from 1.5 to 5.9. There were 13 114 UABSIs in 1.8% of patients who stayed longer than 48 hours on ICU. UABSIs fell from 7.3 (95% confidence interval [CI], 6.9-7.6) to 1.6 (95% CI, 1.5-1.7)/1000 bed days. Adjusting for patient factors, the incidence rate ratio was 0.21 (95% CI, 0.19-0.23, P < .001) from 2007 to 2016. The greatest reduction, comparing rates in 2007/08 and 2015/16, was for MRSA (97%), followed by P. aeruginosa (81%), S. aureus (79%) and Candida spp (72%), with lower reductions for the coliforms (E. coli 57% and Klebsiella 49%).ConclusionsLarge decreases in ICU-acquired infections occurred across the UK ICU network linked with the first few years of a national infection control campaign, but rates have since been static. Further reductions will likely require a new intervention framework.
Project description:Clostridium difficile is an anaerobic, Gram-positive, spore-forming, toxin-secreting bacillus that has long been recognized to be the most common etiologic pathogen of antibiotic-associated diarrhea. C. difficile infection (CDI) is now the most common cause of health care-associated infections in the United States and accounts for 12% of these infections (Magill SS et al., N Engl J Med370:1198-1208, 2014). Among emerging pathogens of public health importance in the United States, CDI has the highest population-based incidence, estimated at 147 per 100,000 (Lessa FC et al., N Engl J Med372:825-834, 2015). In a report on antimicrobial resistance, C. difficile has been categorized by the Centers for Disease Control and Prevention as one of three "urgent" threats (http://www.cdc.gov/drugresistance/threat-report-2013/). Although C. difficile was first described in the late 1970s, the past decade has seen the emergence of hypertoxigenic strains that have caused increased morbidity and mortality worldwide. Pathogenic strains, host susceptibility, and other regional factors vary and may influence the clinical manifestation and approach to intervention. In this article, we describe the global epidemiology of CDI featuring the different strains in circulation outside of North America and Europe where strain NAP1/027/BI/III had originally gained prominence. The elderly population in health care settings has been disproportionately affected, but emergence of CDI in children and healthy young adults in community settings has, likewise, been reported. New approaches in management, including fecal microbiota transplantation, are discussed.
Project description:Infection of the colon with the Gram-positive bacterium Clostridium difficile is potentially life threatening, especially in elderly people and in patients who have dysbiosis of the gut microbiota following antimicrobial drug exposure. C. difficile is the leading cause of health-care-associated infective diarrhoea. The life cycle of C. difficile is influenced by antimicrobial agents, the host immune system, and the host microbiota and its associated metabolites. The primary mediators of inflammation in C. difficile infection (CDI) are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), and, in some bacterial strains, the binary toxin CDT. The toxins trigger a complex cascade of host cellular responses to cause diarrhoea, inflammation and tissue necrosis - the major symptoms of CDI. The factors responsible for the epidemic of some C. difficile strains are poorly understood. Recurrent infections are common and can be debilitating. Toxin detection for diagnosis is important for accurate epidemiological study, and for optimal management and prevention strategies. Infections are commonly treated with specific antimicrobial agents, but faecal microbiota transplants have shown promise for recurrent infections. Future biotherapies for C. difficile infections are likely to involve defined combinations of key gut microbiota.
Project description:We have performed LC-MS based plasma proteomics of twenty febrile patients coming in at Peijas Hospital, Helsinki University Hospital (Vantaa, Finland). At the same time, blood culture was performed to classify the patients to blood culture positive and negative for bloodstream infections. Blood culture negative patients served as controls for the positive ones and these two groups were used for identifying protein profile changes occurring in positive patients. We have subsequently performed various statistical analyses such as principal component analysis as well as pathway analysis by two different methods. We show, in the current study, proteins significantly differing in these two groups as well as dysregulated pathways. These changes seem not to depend on bacterial species as different patients had different blood stream infections. Further, we statistically analyzed the proteomic dataset to find the potential biomarkers which can classify the two classes of patients.
Project description:Sepsis resulting from microbial colonization of the bloodstream is a serious health concern associated with high mortality rates. The objective of this study was to define the physiologic requirements of Citrobacter freundii in the bloodstream as a model for bacteremia caused by opportunistic Gram-negative pathogens. A genetic screen in a murine host identified 177 genes that contributed significantly to fitness, the majority of which were broadly classified as having metabolic or cellular maintenance functions. Among the pathways examined, the Tat protein secretion system conferred the single largest fitness contribution during competition infections and a putative Tat-secreted protein, SufI, was also identified as a fitness factor. Additional work was focused on identifying relevant metabolic pathways for bacteria in the bloodstream environment. Mutations that eliminated the use of glucose or mannitol as carbon sources in vitro resulted in loss of fitness in the murine model and similar results were obtained upon disruption of the cysteine biosynthetic pathway. Finally, the conservation of identified fitness factors was compared within a cohort of Citrobacter bloodstream isolates and between Citrobacter and Serratia marcescens, the results of which suggest the presence of conserved strategies for bacterial survival and replication in the bloodstream environment.