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Although bloodstream infection is widely recognized as an important cause of acute morbidity and mortality, long-term mortality outcomes are less well defined. The objective of this study was to define the early (≤28 days) and late (28 days) mortality and assess determinants of late death following community-onset bloodstream infection.All adult residents of the Calgary Zone who had community-onset bloodstream infections during the period 1 January 2003 and 31 December 2007 were included. The mortality outcome was assessed through to 31 December 2008.A total of 4,553 cases were identified, of which 2,105 (46%) were healthcare-associated and 2,448 (54%) were community-acquired. The 28-day, 90-day, and 365-day all-cause case-fatality rates were 561/4,553 (12%), 780/4,553 (17%), and 1,131 (25%), respectively. Within the first 28 days, the median time to death was 4 (interquartile range [IQR] 1-12) days, with 158 (28%) and 212 (38%) of early (≤28-day) deaths occurring by days 1 and 2, respectively. Among survivors to 28 days (n = 3,992), 570 (14%) suffered late 1-year mortality (i.e., death occurred between 29 and 365 days postinception). The most common causes of death in this cohort as listed by the vital statistics data were malignancy in 220 (39%), cardiovascular in 135 (24%), and infection-related in 37 (7%). Older age, higher Charlson score, prolonged initial admission duration, and healthcare-associated and polymicrobial infections were independently associated with late 1-year mortality.Community-onset bloodstream infection is associated with major early and late mortality.

Theoretically there are several ways to prevent pyelonephritis and renal scarring caused by P-fimbriated Escherichia coli. Screening for individuals at risk, e.g. those carrying P-fimbriated pyelonephritogenic E. coli or those with high receptor density on their uroepithelial cells, could perhaps define a population where prophylaxis with a receptor analogue or vaccination with P-fimbriae may be relevant. Epidemiological measures in neonatal and maternity wards may prevent the nosocomial spread of virulent bacteria and reduce the number of colonized infants. However, no such methods have so far had any proven clinical relevance, and today, the important concern is still to try by conventional means--as we have always done--to get an early diagnosis and to treat the patient without delay.

Fecal colonization with P-fimbriated Escherichia coli has caused epidemic outbreaks of extraintestinal E. coli infections in the neonatal unit of Danderyd Hospital. The aerobic fecal flora was therefore studied in 1,955 newborn children born at Danderyd Hospital during a period of 2.5 years. E. coli was found in 58% of the maternity ward children and in 57% of the neonatal unit children. A P-fimbriated strain was found in 12% and 17% of the children, respectively (p less than 0.01). There was a significant increase in the frequency of children colonized with E. coli, and especially P-fimbriated E. coli, with length of stay in the neonatal unit. There was a statistical correlation between bed occupancy and colonization with P-fimbriated E. coli (r = 0.46, p less than 0.01) during this study period. We found an incidence of P-fimbriated E. coli of 10 to 20% among the E. coli strains isolated from the fecal specimens which we regard as the baseline incidence.

More than 95% of acute non-obstructive pyelonephritis cases in children are caused by P-fimbriated Escherichia coli. Uroepithelial cells from individuals prone to urinary tract infections bind such bacteria more avidly than do cells from healthy controls. A high density of receptors for P-fimbriae on cells of the urinary tract and kidney may thus be an important host factor in the acquisition of upper urinary tract infections. In this communication we are describing methods to determine the densities and localization of P-fimbriae receptors on mammalian cells. To determine the receptor density on cells in suspension, the cells were incubated with fluorescein-labelled P-fimbriated E. coli. They were then subjected to fluorescence-activated cell sorting (FACS) analysis which monitors both the size and the relative fluorescence of each cell. FACS analysis proved versatile for rapid and specific analyses of P-fimbriae receptor densities on large numbers of any chosen type of cell. The fluorescein-labelled P-fimbriated E. coli were also useful in localizing P-fimbriae receptors in tissues. These techniques are not limited to the assessment of P-fimbriae receptor densities and tissue localization but open up new aspects for studies of the specificities involved in the interactions between other microorganisms (e. g. parasites, bacteria and virus) and their host cells.

Most (greater than 90%) Escherichia coli strains isolated from children with acute non-obstructive pyelonephritis exhibit a specific type of filamentous protein appendage known as P-fimbriae. These fimbriae enable the bacterium to adhere to human uroepithelial cells by the specific recognition of and binding to a particular class of glycosphingolipids correlated to the human P-blood group antigens. In this paper a new method for the rapid and reliable identification of such P-fimbriated pyelonephritogenic bacteria is described. The method is based on particles to which the minimal glycoside receptor structure recognized by P-fimbriae is attached. Mixing these receptor-containing particles with P-fimbriated bacteria results in a strong and immediate agglutination reaction. The specificity and sensitivity of this new particle agglutination test proved to be superior to the haemagglutination assay previously used.

Pyelonephritogenic Escherichia coli isolates were found to be equal in their ability to adhere to uroepithelial cells and to cause agglutination specific for human erythrocytes. This adhesive capacity was not affected by D-mannose and was found to be mediated by a new class of E. coli fimbriae named P-fimbriae. Using human erythrocytes of different blood groups, we found the receptor molecules for P-fimbriae to be associated with the P blood group antigens, i. e. glycosphingolipids corresponding to the P blood group antigens P, P1 and Pk. By agglutination studies of erythrocytes with various set-ups of these antigens as well as by inhibition studies using synthetic saccharide derivatives and by coating non-agglutinable erythrocytes with a synthetic glycolipid, the minimal receptor structure was identified as the alpha-D-Galp-(1-4)-beta-D-Galp moiety of the carbohydrate portion of these glycosphingolipids. Similar experiments on isolated uroepithelial cells proved that these glycosphingolipids also constitute the receptors in the urinary tract.

An experimental pyelonephritis model was developed in monkeys (Macaca fascicularis) using P-fimbriatedEscherichia coli as the infecting organism. The relevant receptor molecules for P-fimbriae were also shown to be present inMacaca fascicularis. Atraumatic administration of P-fimbriatedE. coli into the ureter induced a ureteritis followed by acute and chronic pyelonephritis. The decisive role of P-fimbriae as an adhesive virulence factor was proven by the receptor blockade of P-fimbriae-mediated bacterial adhesion by a synthetic receptor analogue (α-D-Galp-(1–4)-β-D-Galp-1-OMe), which was administered into the ureter together with the challenge bacteria. On the basis of these and other findings, the role of reflux and pyelonephritis in relation to renal scarring is discussed in this paper. It is proposed that minor transitional vesicoureteral reflux together with the adhesive property of P-fimbriatedE. coli and their ability to induce ureteritis might constitute an alternative mechanism to gross reflux by which bacteria ascend to the kidney. These findings and the fact that intestinal colonization with P-fimbriatedE. coli coincides with the disease have opened up new prophylactic and therapeutic possibilities.

A slide agglutination test to detect P-fimbriated Escherichia coli was developed by attaching glycosides containing the relevant receptor structure (alpha-D-Galp-(1-4)-beta-D-Galp) to particles. A suspension of these particles agglutinates within ten seconds when mixed with P-fimbriated bacteria. The test is named the P-specific particle agglutination test (PPA test). The PPA test is more sensitive than the haemagglutination assays previously used. The exclusive specificity of the PPA test also allows the detection of P-fimbriae on strains which additionally possess other fimbriae (e.g. X-fimbriae). Using this test, the frequency of P-fimbriated E. coli in children with acute non-obstructive pyelonephritis was shown to exceed 95%. In lower urinary tract infections the frequency of P-fimbriated E. coli was approximately 20%. Moreover, children with acute pyelonephritis were also found to be heavily colonized in both the periurethral area and the intestine with the identical P-fimbriated E. coli strain.

An experimental pyelonephritis model was developed in monkeys (Macaca fascicularis) using P-fimbriated Escherichia coli as the infecting organism. The relevant receptor molecules for P-fimbriae were also shown to be present in Macaca fascicularis. Atraumatic administration of P-fimbriated E. coli into the ureter induced a ureteritis followed by acute and chronic pyelonephritis. The decisive role of P-fimbriae as an adhesive virulence factor was proven by the receptor blockade of P-fimbriae-mediated bacterial adhesion by a synthetic receptor analogue (alpha-D-Galp-(1-4)-beta-D-Galp-1-OMe), which was administered into the ureter together with the challenge bacteria. On the basis of these and other findings, the role of reflux and pyelonephritis in relation to renal scarring is discussed in this paper. It is proposed that minor transitional vesicoureteral reflux together with the adhesive property of P-fimbriated E. coli and their ability to induce ureteritis might constitute an alternative mechanism to gross reflux by which bacteria ascend to the kidney. These findings and the fact that intestinal colonization with P-fimbriated E. coli coincides with the disease have opened up new prophylactic and therapeutic possibilities.