epiglucan and Bacteremia

Candidemia is associated with a heavy burden of morbidity and mortality in hospitalized patients. The availability of blood culture results could require up to 48-72 h after blood draw; thus, early treatment decisions are made in the absence of a definite diagnosis.. In this retrospective study, we assessed the performance of different supervised machine learning algorithms for the early differential diagnosis of candidemia and bacteremia in adult patients on a large dataset automatically extracted within the AUTO-CAND project.. Overall, 12,483 episodes of candidemia (1275; 10%) or bacteremia (11,208; 90%) were included in the analysis. A random forest classifier achieved the best diagnostic performance for candidemia, with sensitivity 0.98 and specificity 0.65 on the training set (true skill statistic [TSS] = 0.63) and sensitivity 0.74 and specificity 0.57 on the test set (TSS = 0.31). Then, the random classifier was trained in the subgroup of patients with available serum β-D-glucan (BDG) and procalcitonin (PCT) values by exploiting the feature ranking learned in the entire dataset. Although no statistically significant differences were observed from the performance measures obtained by employing BDG and PCT alone, the performance measures of the classifier that included the features selected in the entire dataset, plus BDG and PCT, were the highest in most cases.. Random forest classifiers trained on large datasets of automatically extracted data have the potential to improve current diagnostic algorithms for candidemia. However, further development through implementation of automatically extracted clinical features may be necessary to achieve crucial improvements.

Topics: Adult; Bacteremia; beta-Glucans; Candidemia; Early Diagnosis; Humans; Machine Learning; Procalcitonin; Retrospective Studies

Topics: Adult; Aged; Antifungal Agents; Bacteremia; beta-Glucans; Candidemia; Female; Humans; Intensive Care Units; London; Male; Middle Aged; Point-of-Care Testing; Practice Patterns, Physicians'; Proteoglycans; Reagent Kits, Diagnostic; Retrospective Studies

This study aimed to assess the combined performance of serum (1,3)-β-D-glucan (BDG) and procalcitonin (PCT) for the differential diagnosis between candidaemia and bacteraemia in three intensive care units (ICUs) in two large teaching hospitals in Italy.. From June 2014 to December 2015, all adult patients admitted to the ICU who had a culture-proven candidaemia or bacteraemia, as well as BDG and PCT measured closely to the time of the index culture, were included in the study. The diagnostic performance of BDG and PCT, used either separately or in combination, was assessed by calculating the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios (LR+ and LR-). Changes from pre-test probabilities to post-test probabilities of candidaemia and bacteraemia were inferred from Fagan's nomograms.. One hundred and sixty-six patients were included, 73 with candidaemia (44%) and 93 with bacteraemia (56%). When both markers indicated candidaemia (BDG ≥80 pg/ml and PCT <2 ng/ml) they showed higher PPV (96%) compared to 79% and 66% for BDG or PCT alone, respectively. When both markers indicated bacteraemia (BDG <80 pg/ml and PCT ≥2 ng/ml), their NPV for candidaemia was similar to that of BDG used alone (95% vs. 93%). Discordant BDG and PCT results (i.e. one indicating candidaemia and the other bacteraemia) only slightly altered the pre-test probabilities of the two diseases.. The combined use of PCT and BDG could be helpful in the diagnostic workflow for critically ill patients with suspected candidaemia.

Topics: Adult; Aged; Bacteremia; beta-Glucans; Biomarkers; Calcitonin; Candidemia; Diagnosis, Differential; Female; Humans; Intensive Care Units; Italy; Male; Middle Aged; Proteoglycans

The value of (1 → 3)-beta-D-glucans (BG) and galactomannan (GM) assays on diagnostic invasive fungal infections (IFIs) has been observed in adult ICU and in children with hematological malignancies. Only scant data evaluated non-hematological in pediatric intensive care unit (PICU). Here, we retrospectively analyzed the role of bacterial infection to the reactivity of BG and GM assays in PICU. The results showed that the overall prevalence of bacteremia was 13.8% (65/470). The most common underlying disease was pneumonia (81.8%), followed by congenital heart disease (43.2%). The median levels of GM and range for each group [A: without bacterial infection nor IFIs (n = 151); B, patients with bacterial infection (n = 36); C, patients with bacterial infection and IFIs (n = 8)] were, respectively: 0.14 (0.01-1.34), 0.21 (0.06-1.34), 0.14 (0.02-0.99). No significant difference was found among three groups (P = 0.66). The median levels of BG and range for each group (A, B, C) were, respectively: 50.00 pg/mL (16.20-548.20 pg/mL), 50.00 pg/mL (16.10-597.60 pg/mL), 268.7 pg/mL (50.9-4224.00 pg/mL). Patients with bacteremia and IFIs showed significantly higher BG levels than these who with or without bacteremia (P = 0.003), but there was no significant difference between control subjects and patients with bacteremia group. We also observed the GM and BG levels in Gram-negative and Gram-positive groups. No significant difference was found between two groups. In conclusions, the results showed that bacteremia was unlikely cause of false-positive results of the BG and GM assays in PICU.

Topics: Bacteremia; beta-Glucans; Child; Child, Preschool; Female; Galactose; Humans; Infant; Intensive Care Units, Pediatric; Invasive Fungal Infections; Male; Mannans; Retrospective Studies

Bacteraemia was reported to be associated with false-positive 1→3-β-D-glucan (BG) assay results. We thus prospectively assessed the reactivity of the BG (Fungitell) in samples of 21 adults with bacteraemia: . BG was negative in all and is s therefore an unlikely cause of false positive BG in adults.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; beta-Glucans; Humans; Middle Aged; Prospective Studies; Proteoglycans; Serum; Young Adult

There are discrepancies in the retrospective studies published in literature of whether or not bacteraemia could lead to false positivity of 1,3-β-D (BG) glucan assay. We performed, for the first time, a prospective study evaluating the role of bacterial bloodstream infection to the reactivity of BG assay. Twenty-six episodes of bacteraemia that occurred in high-risk haematological patients were included in our study. Consecutive BG levels >80 pg ml(-1) were required for test positivity. Only 2 of 26 patients were BG positive - both with IFDs. Thus, we prospectively did not prove bacteraemia as the source of cross reactivity of BG assay in haematological patients.

Topics: Anti-Bacterial Agents; Bacteremia; Bacteria; beta-Glucans; Humans; Prospective Studies; Retrospective Studies

The diagnosis of neonatal invasive Candida infections (ICIs) is problematic because the clinical signs are not specific and blood cultures are rarely positive. Hence, new diagnostic markers are needed.. To assess the contribution of serum (1-3)-β-d-glucan (BDG) levels to the diagnosis of neonatal ICIs and to analyse the change in this parameter during antifungal therapy.. This retrospective study (December 2010-March 2012) was performed at Amiens University Medical Center (Amiens, France). We included newborns in whom a BDG assay was performed for a suspected ICI and classified as infected (n = 18) or non-infected (n = 43).. Sixty-one patients (median (IQR) gestational age: 28.5 weeks (26.7-30.6); birth weight: 1000 g (910-1440)) were included. The BDG level was higher in the infected group (364 pg/ml (131-976) vs. 89 pg/ml (30-127); p < 0.001). The optimal BDG cut-off for distinguishing between non-infected and infected patients was 125 pg/ml (Se = 84%, Sp = 75%). The BDG level fell over the course of antifungal therapy.. Our study results suggest that BDG levels were increased in neonatal invasive Candida infections (cut-off for BDG positivity > 125 pg/ml). The change in the serum BDG levels may be of value in evaluating the efficacy of antifungal therapy.

Topics: Antifungal Agents; Bacteremia; beta-Glucans; Biomarkers; Candidiasis; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pregnancy; Proteoglycans; Retrospective Studies

Acinetobacter baumannii has emerged as a highly troublesome, global pathogen. Treatment is complicated by high levels of antibiotic resistance, necessitating alternative means to prevent or treat A. baumannii infections. We evaluated an immunotherapeutic approach against A. baumannii, focusing on the surface polysaccharide poly-N-acetyl-β-(1-6)-glucosamine (PNAG). We used a synthetic oligosaccharide of 9 monosaccharide units (9Glc-NH(2)) conjugated to tetanus toxoid (TT) to induce antibodies in rabbits. In the presence of complement and polymorphonuclear cells, antisera to 9Glc-NH(2)-TT mediated the killing of A. baumannii S1, a high-PNAG-producing strain, but not its isogenic PNAG-negative, in-frame deletion mutant strain, S1 Δpga. Complementing the pgaABCD locus in trans in the shuttle vector pBAD18kan-ori, plasmid Δpga-c, restored the high levels of killing mediated by antibody to PNAG observed with the wild-type S1 strain. No killing was observed when normal rabbit serum (NRS) or heat-inactivated complement was used. Antiserum to 9Glc-NH(2)-TT was highly opsonic against an additional four unrelated multidrug-resistant clinical isolates of A. baumannii that synthesize various levels of surface PNAG. Using two clinically relevant models of A. baumannii infection in mice, pneumonia and bacteremia, antisera to 9Glc-NH(2)-TT significantly reduced levels of A. baumannii in the lungs or blood 2 and 24 h postinfection, respectively, compared to levels of control groups receiving NRS. This was true for all four A. baumannii strains tested. Overall, these results highlight the potential of PNAG as a vaccine component for active immunization or as a target for passive antibody immunotherapy.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Antibodies, Bacterial; Bacteremia; beta-Glucans; Female; Immune Sera; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Rabbits

To diagnose invasive fungal infections, the detection of (1 → 3)-β-d-glucan in serum has shown variable specificity, depending on the targeted population. Several circumstances for false-positive results of beta-glucan tests have been identified, among which are severe bacterial infections. In this study, we measured (1 → 3)-β-d-glucan by the Fungitell test in the serum of 62 patients (one serum sample tested per patient) for whom invasive fungal infection was not suspected: 19 control subjects and 43 patients with bacteraemia. The test was interpretable for 58 sera: all 19 control subjects had negative beta-glucan test; among the 39 bacteraemic patients, we report 16 false-positive results. For the 22 patients undergoing bacteraemia due to Gram-negative bacilli, we observed 13 false-positive results (59%). Among the 17 patients with bloodstream infection involving Gram-positive cocci, three false-positive tests were recorded, but none in the eight cases of Streptococcus pneumoniae bacteraemia. Statistical analysis showed that beta-glucan levels were significantly higher in patients with Gram-negative bacilli bloodstream infection in comparison to those with bacteraemia due to Gram-positive cocci. These results were independent from other previously described causes for false-positive beta-glucan tests. These data might help physicians to interpret positive beta-glucan detection when an invasive fungal infection is suspected, especially for patients with bacterial infections.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; beta-Glucans; Child, Preschool; False Positive Reactions; Female; France; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Infant, Newborn; Male; Middle Aged; Predictive Value of Tests; Proteoglycans; Reagent Kits, Diagnostic; Retrospective Studies; Sensitivity and Specificity; Time Factors; Young Adult

The aim was to evaluate the role of procalcitonin (PCT) and (1-3)-β-D-glucan (BG) tests for early detection or exclusion of central venous catheter-related bloodstream infections (CRBSI) in patients after orthotopic liver transplantation (OLT).. Fifty-five patients with clinically suspected CRBSI were assessed after OLT in this prospective study. On the day of clinical suspicion of CRBSI, blood samples were obtained from central venous catheters and a peripheral vein for blood cultures and from a peripheral vein for PCT and BG tests. Plasma PCT and BG values were measured by using an immunoluminometric assay and Fungitell BG assay, respectively. No prisoners or organs from prisoners were used in this study.. Twenty-five patients (45%) were diagnosed with CRBIS. Among them, 13 (52%) displayed gram-positive bacteriemia, 11 (44%) gram-negative bacteriemia, and 1 (4%) fungemia. The PCT values were higher in CRBSI than in non-CRBSI patients (P = .003). CRBSI patients did not show significant increases in plasma BG values compared with non-CRBSI subjects (P = .051). PCT and BG area under receiver operating characteristic curves were 0.840 and 0.486, respectively. Sensitivity, specificity, and positive and negative predictive values of a PCT of ≥ 3.1 ng/mL for the diagnosis of CRBSI were 0.72, 0.87, 0.82, and 0.79, respectively. The figures for a BG of ≥ 83 pg/mL were 0.32, 0.90, 0.73, and 0.61, respectively. Among the 24 patients with bacteria infections, PCT was higher in patients with gram-negative than those with gram-positive bacterial infections (P = .022).. We concluded that the PCT assay may be a useful rapid diagnostic adjunct for the diagnosis of suspected CRBSI in OLT patients.

Topics: Bacteremia; beta-Glucans; Calcitonin; Calcitonin Gene-Related Peptide; Catheters, Indwelling; Fungemia; Humans; Liver Transplantation; Protein Precursors; Proteoglycans

Topics: Bacteremia; beta-Glucans; Cross Reactions; Diagnosis, Differential; False Positive Reactions; Humans; Mycoses; Proteoglycans; Pseudomonas aeruginosa; Pseudomonas Infections

Staphylococcus aureus and Staphylococcus epidermidis both synthesize the surface polysaccharide poly-N-acetyl-beta-(1-6)-glucosamine (PNAG), which is produced in vitro with a high level (>90%) of the amino groups substituted by acetate. Here, we examined the role of the acetate substituents of PNAG in generating opsonic and protective antibodies. PNAG and a deacetylated form of the antigen (dPNAG; 15% acetylation) were conjugated to the carrier protein diphtheria toxoid (DT) and used to immunize animals. Mice responded in a dose-dependent fashion to both conjugate vaccines, with maximum antibody titers observed at the highest dose and 4 weeks after the last of three weekly immunizations. PNAG-DT and dPNAG-DT vaccines were also very immunogenic in rabbits. Antibodies raised to the conjugate vaccines in rabbits mediated the opsonic killing of various staphylococcal strains, but the specificity of the opsonic killing was primarily to dPNAG, as this antigen inhibited the killing of S. aureus strains by both PNAG- and dPNAG-specific antibodies. Passive immunization of mice with anti-dPNAG-DT rabbit sera showed significant levels of clearance of S. aureus from the blood (54 to 91%) compared to control mice immunized with normal rabbit sera, whereas PNAG-specific antibodies were ineffective at clearing S. aureus. Passive immunization of mice with a goat antiserum raised to the dPNAG-DT vaccine protected against a lethal dose of three different S. aureus strains. Overall, these data show that immunization of animals with a conjugate vaccine of dPNAG elicit antibodies that mediated opsonic killing and protected against S. aureus infection, including capsular polysaccharide types 5 and 8 and an untypable strain.

Topics: Acetylation; Animals; Antibodies, Bacterial; Bacteremia; beta-Glucans; Immunization, Passive; Immunoglobulin G; Mice; Opsonin Proteins; Phagocytes; Rabbits; Staphylococcal Infections; Staphylococcal Vaccines; Staphylococcus aureus; Vaccines, Conjugate

The contribution of the Staphylococcus aureus surface polysaccharide poly-N-acetylglucosamine (PNAG) to virulence was evaluated in three mouse models of systemic infection: bacteremia, renal abscess formation, and lethality following high-dose intraperitoneal (i.p.) infection. Deletion of the intercellular adhesin (ica) locus that encodes the biosynthetic enzymes for PNAG production in S. aureus strains Mn8, Newman, and NCTC 10833 resulted in mutant strains with significantly reduced abilities to maintain bacterial levels in blood following intravenous or i.p. injection, to spread systemically to the kidneys following i.p. injection, or to induce a moribund/lethal state following i.p. infection. In the bacteremia model, neither growth phase nor growth medium used to prepare the S. aureus inoculum affected the conclusion that PNAG production was needed for full virulence. As the SarA regulatory protein has been shown to affect ica transcription, PNAG synthesis, and biofilm formation, we also evaluated S. aureus strains Mn8 and 10833 deleted for the sarA gene in the renal infection model. A decrease in PNAG production was seen in sarA mutants using immunoblots of cell surface extracts but was insufficient to reduce the virulence of sarA-deleted strains in this model. S. aureus strains deleted for the ica genes were much more susceptible to antibody-independent opsonic killing involving human peripheral blood leukocytes and rabbit complement. Thus, PNAG confers on S. aureus resistance to killing mediated by these innate host immune mediators. Overall, PNAG production by S. aureus appears to be a critical virulence factor as assessed in murine models of systemic infection.

Topics: Adhesins, Bacterial; Animals; Bacteremia; Bacterial Proteins; beta-Glucans; Disease Models, Animal; Gene Deletion; Immunity, Innate; Mice; Phagocytosis; Staphylococcal Infections; Staphylococcus aureus; Virulence

The antimicrobial effect of soluble beta-1,3-D-glucan from Sclerotinia sclerotiorum (SSG) was examined in mice experimentally infected intraperitoneally (i.p.) with Streptococcus pneumoniae serotypes 4 and 6B. SSG was administered i.p. either 3 days before challenge or 3-48 h after challenge. The number of bacteria in blood samples and the mouse survival rates were recorded. Pre-challenge SSG administration protected dose-dependently against both S. pneumoniae type 4 and 6B infections. SSG injected 24 h post-challenge had a curative effect against type 6B but not type 4 pneumococcal infection. The data demonstrate that SSG administered systemically protects against pneumococcal infection in mice.

Topics: Animals; Antibodies, Bacterial; Bacteremia; beta-Glucans; Colony Count, Microbial; Female; Glucans; Humans; Mice; Pneumococcal Infections; Streptococcus pneumoniae; Survival Rate