The public health challenge of obesity: is it the new smoking?

This article considers the complexity of obesity and its health implications, highlighting its implications for community practitioners

Is the GehD lipase from Staphylococcus epidermidis a collagen binding adhesin

The opportunistic human pathogen Staphylococcus epidermidis is the major cause of nosocomial biomaterial infections. S. epidermidis has the ability to attach to indwelling materials coated with extracellular matrix proteins such as fibrinogen, fibronectin, vitronectin, and collagen. To identify the proteins necessary for S. epidermidis attachment to collagen, we screened an expression library using digoxigenin-labeled collagen as well as two monoclonal antibodies generated against the Staphylococcus aureus collagen-adhesin, Cna, as probes. These monoclonal antibodies recognize collagen binding epitopes on the surface of S. aureus and S. epidermidis cells. Using this approach, we identified GehD, the extracellular lipase originally found in S. epidermidis 9, as a collagen-binding protein. Despite the monoclonal antibody cross-reactivity, the GehD amino acid sequence and predicted structure are radically different from those of Cna. The mature GehD circular dichroism spectra differs from that of Cna but strongly resembles that of a mammalian cell-surface collagen binding receptor, known as the alpha(1) integrin I domain, suggesting that they have similar secondary structures. The GehD protein is translated as a preproenzyme, secreted, and post-translationally processed into mature lipase. GehD does not have the conserved LPXTG C-terminal motif present in cell wall-anchored proteins, but it can be detected in lysostaphin cell wall extracts. A recombinant version of mature GehD binds to collagens type I, II, and IV adsorbed onto microtiter plates in a dose-dependent saturable manner. Recombinant, mature GehD protein and anti-GehD antibodies can inhibit the attachment of S. epidermidis to immobilized collagen. These results provide evidence that GehD may be a bi-functional molecule, acting not only as a lipase but also as a cell surface-associated collagen adhesin

Porting TELEMAC-MASCARET to OPENPOWER and experimenting GPU offloading to accelerate the TOMAWAC module

Hydrodynamic

677. Systematic Review of the Early Use Experince of Cefiderocol in Real World Practice

Abstract Background Gram-negative bacteria (GNB) with resistance to carbapenems is a growing global public health concern. The World Health Organisation have listed three priority GNB pathogens for the development of novel antimicrobial agents; Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales. The purpose of this systematic review (SR) was to report evidence on the use of cefiderocol (FDC), a siderophore cephalosporin, for patients with GNB infections in compassionate use or expanded access settings. Methods Searches were undertaken to identify relevant evidence up to December 2021. Two independent reviewers screened the records retrieved for relevance to the SR with disagreements adjudicated by a third reviewer. Patients receiving FDC in a compassionate use, expanded access setting or those with limited treatment options for the treatment of GNB infection were eligible. Eligible case reports and case series were assessed for quality using predefined tools and data were extracted (by a single reviewer with data checking performed by a second reviewer), tabulated and summarised. Results Forty-four studies (n=150 patients) were identified reporting the use of FDC; 3 case series studies and 41 case reports. The most commonly reported pathogens were P. aeruginosa (41.3%), A. baumannii (36.0%) and A. xylosoxidans (14.3%). The diagnoses varied widely across the included patients. All patients were administered FDC at a dose between 750 mg and 2 g per day on various schedules, adjusted for renal function for between one and six weeks. Clinical cure was reported in 137 patients using author-specified definitions with 74 patients (54.0%) reporting clinical cure and 18 (13.1%) reporting failure. Microbiological eradication was reported in 78 patients of whom 56 (71.8%) reported success, while 22 (28.2%) reported failure. For mortality (n=123) 80 patients (65.0%) remained alive at the end of treatment, while 43 (35.0%) died. Adverse event (AE) data was reported for 53 patients of whom 13 (24.5%) reported AEs, while 40 (75.5%) did not. See Table 1.0. Conclusion FDC is a promising therapy for patients with GNB infections with limited treatment options. Real world practice shows a high microbiological eradication rate and a small number of AEs. Disclosures Carlo Tascini, n/a, Shionogi: Grant/Research Support Aurelien Dinh, Professor of Infectious Disease, Shionogi: Advisor/Consultant|Shionogi: Board Member Christopher M. Longshaw, PhD, Shionogi: Employee Anita C. Fitzgerald, MPH, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an associate, to conduct the systematic review we are submitting to IDWeek Hannah Wood, BA MA, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee, to conduct the systematic review we are submitting to IDWeek Jacoby Vivien M. Patterson, MA Cantab, MB BChir, FFPH MD, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an associate, to conduct the systematic review we are submitting to IDW Deborah Watkins, MSc, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee, to conduct the systematic review we are submitting to IDWeek Katy Wilson, LLM, Shionogi: Shionogi commissioned York Health Economics Consortium of which I am an employee to conduct the systematic review we are submitting to IDWeek Karan Gill, Master of Science, Shionogi: Employee

Unsaturated fatty acids are inhibitors of bacterial conjugation

This report describes a high-throughput assay to identify substances that reduce the frequency of conjugation in Gram-negative bacteria. Bacterial conjugation is largely responsible for the spread of multiple antibiotic resistances in human pathogens. Conjugation inhibitors may provide a means to control the spread of antibiotic resistance. An automated conjugation assay was developed that used plasmid R388 and a laboratory strain of Escherichia coli as a model system, and bioluminescence as a reporter for conjugation activity. Frequencies of conjugation could be measured continuously in real time by the amount of light produced, and thus the effects of inhibitory compounds could be determined quantitatively. A control assay, run in parallel, allowed elimination of compounds affecting cell growth, plasmid stability or gene expression. The automated conjugation assay was used to screen a database of more than 12 000 microbial extracts known to contain a wide variety of bioactive compounds (the NatChem library). The initial hit rate was 1·4 %. From these, 48 extracts containing active compounds and representing a variety of organisms and extraction conditions were subjected to fractionation (24 fractions per extract). The 52 most active fractions were subjected to a secondary analysis to determine the range of plasmid inhibition. Plasmids R388, R1 and RP4 were used as representatives of a variety of plasmid transfer systems. Only one fraction (of complex composition) affected transfer of all three plasmids, while four other fractions were active against two of them. Two separate compounds were identified from these fractions: linoleic acid and dehydrocrepenynic acid. Downstream analysis showed that the chemical class of unsaturated fatty acids act as true inhibitors of conjugation

Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013

Clostridium difficile infection (CDI) is the major cause of infective diarrhoea in healthcare environments. As part of the EUCLID study, the largest C. difficile epidemiological study of its type, PCR-ribotype distribution of C. difficile isolates in Europe was investigated. PCR-ribotyping was performed on 1196 C. difficile isolates from diarrhoeal samples sent to the European co-ordinating laboratory in 2012–13 by 482 participating hospitals from 19 European countries. A total of 125 ribotypes were identified, of which ribotypes 027 (18.6%), 001/072 (11.2%) and 014 (7.0%) were the most prevalent. Distinct regional patterns of ribotype distribution were noted in Northern, Western, Southern and Eastern Europe. Of 596 isolates from patients with toxin-positive stools (confirmed CDI), ribotype 027 accounted for 27.8% of infections in patients aged 2–<65 years, but the prevalence decreased in those aged ≥65 years (14.3%) and further decreased in those aged ≥81 years (9.2%). The prevalence of ribotype 027 (but not other epidemic strains) was inversely proportional to overall ribotype diversity (R2=0.717). The EUCLID study highlights an increased diversity of C. difficile ribotypes across Europe compared with previous studies, with considerable inter-country variation in ribotype distribution. Continuous surveillance programmes are necessary to monitor the changing epidemiology of C. difficil

Replacement of Enterococcus faecalis by Enterococcus faecium as the predominant enterococcus in UK bacteraemias

Objectives To review temporal changes in the proportions of different Enterococcus species recorded in two UK bacteraemia surveillance systems. Antibiotic resistance trends were also considered. Methods We reviewed data for enterococci from 2001 to 2019 in: (a) the BSAC Resistance Surveillance Programme, which collected up to 7–10 bloodstream enterococci every year from each of 23–39 hospitals in the UK and Ireland and tested these centrally; and (b) PHE bacteraemia surveillance, using routine results from NHS microbiology laboratories in England. Results BSAC surveillance, based upon 206–255 enterococci each year (4486 in total), indicated that the proportion of Enterococcus faecium rose from 31% (212/692) in the period 2001–3 to 51% (354/696) in the period 2017–19, balanced by corresponding falls in the proportion of Enterococcus faecalis. PHE surveillance provided a larger dataset, with >5000 enterococcus reports per year; although its identifications are less precise, it too indicated a rise in the proportion of E. faecium. BSAC surveillance for E. faecium indicated no consistent trends in resistance to ampicillin (≥86% in all years), vancomycin (annual rates 19%–40%) or high-level resistance to gentamicin (31%–59%). Resistance to vancomycin remained <4% in E. faecalis in all years, whilst high-level resistance to gentamicin fell, perhaps partly reflecting the decline of two initially prevalent gentamicin- and ciprofloxacin-resistant clones. Conclusions Both surveillance systems indicate a growing proportion of E. faecium in enterococcal bloodstream infections. This is important because fewer therapeutic options remain against this frequently multiresistant species than against E. faecalis