Search Results (6)

Background: 1, 3-ß-D-Glucan (BDG) is an antigen present in the cell wall of many pathogenic fungi and is used as a marker for the early diagnosis of candidemia and discontinuation of empirical treatment. Changes in the epidemiology of Candida species might have a negative impact on the performance of serum BDG. The aim of this study was to analyze the performance of BDG in candidemia diagnosis focusing on species-specific differences in BDG sensitivity and BDG levels. Methods: The PRISMA system was used for the systematic search. The following databases were searched for articles published from January 2010 to November 2023: PubMed, Science Direct, and Scopus. Results: A total of 21 studies that met the inclusion criteria were included, reporting data from 1633 patients with candidemia; 11 reported both sensitivity and specificity, 15 reported species-specific sensitivity, and nine reported species-specific BDG levels. The pooled sensitivity of BDG in all studies was 0.73 (95% confidence interval (CI), 0.66-0.80), while the pooled sensitivity and specificity in 11 studies were 0.81 (95% CI 0.73-0.89) and 0.80 (95% CI 0.74-0.87). BDG pooled sensitivity (all assays) and BDG levels (for assays with cutoff of 80 pg/mL) were the highest in C. krusei (currently Pichia kudriavzevii) and the lowest in C. auris: 0.76 and 417 pg/mL for C. krusei, 0.73 and 345 pg/mL for C. albicans, 0.74 and 356 pg/mL for C. glabrata (currently Nakaseomyces glabrata), 0.70 and 324 pg/mL for C. tropicalis, 0.63 and 95 pg/mL for C. parapsilosis, 0.51 and 62 pg/mL for C. auris, and 0.44 and 79 pg/mL for other Candida species. These differences were statistically significant for BDG sensitivity and levels of C. albicans, C. glabrata, C. krusei, and C. tropicalis compared to C. auris, C. parapsilosis, and other Candida species. Conclusion: The sensitivity of BDG in candidemia diagnosis depends on the Candida species, with the lowest being for C. auris and C. parapsilosis. This might have a clinical impact in centers where these species are prevalent. Full article

Background and Objectives: Insulin sensitivity has been shown to decrease during the day among persons at risk of type 2 diabetes (T2DM). It remains to be established whether this also results in differences in glycaemic response to meals rich in carbohydrates, e.g., bread meals. Hence, we determined whether diurnal differences between morning and evening meals containing breads could be observed among persons at risk of T2DM consuming different breads as part of their habitual diet. Methods: Analysis based on data from a multicentre randomised controlled trial (CarbHealth) conducted among participants with prediabetes at four study sites (Germany, Norway, Sweden) who received either a ß-glucan-enriched bread or a non-enriched wholegrain control bread to replace their habitually consumed bread for 16 weeks. In Paderborn, Germany, participants wore a continuous glucose monitoring device during weeks 1 and 16. The incremental area under the curve (iAUC) in the two hours following a bread meal in the morning or evening was determined and compared using a t-test. Morning bread meals were defined as meals consumed between 06.00 and 11.00 a.m., and evening bread meals referred to meals consumed between 05.00 and 10.00 p.m. Results: Out of 47 participants, 20 and 13 who consumed ß-glucan-enriched bread or wholegrain bread as part of their meals both in the morning and evening were considered. In persons consuming the ß-glucan bread, the iAUC of evening bread meals was higher than in morning bread meals in week 1 only (evening 2 h iAUC = 1561 [±760] mg/dL vs. morning 2 h iAUC = 1181 [±500] mg/dL, p = 0.03). In the control bread-group, the iAUC was higher in evening bread meals than in morning bread meals in week 16 (evening 2 h iAUC = 2445 [±1894] mg/dL vs. morning 2 h iAUC = 1764 [±1314] mg/dL, p = 0.04). Discussion: These preliminary data from a small sample of persons with prediabetes indicate that diurnal differences in carbohydrate consumption may extend to the context of habitual carbohydrate-rich meals. If replicated, persons at risk of T2DM should be discouraged from consuming large amounts of bread in the evening. Full article

According to the immunodepression status, the diagnosis of Pneumocystis jirovecii pneumonia (PjP) may be difficult. Molecular methods appear very sensitive, but they lack specificity because Pj DNA can be detected in Pneumocystis-colonized patients. The aim of this study was to evaluate the value of a serum ß-d-Glucan (BDG) assay for the diagnosis of PjP in a large cohort of HIV-negative and HIV-positive patients, either as a first-line diagnostic test for PjP or as a tool to distinguish between colonization and PjP in cases of low fungal load. Data of Pj qPCR performed on bronchopulmonary specimens over a 3-year period were retrieved retrospectively. For each result, we searched for a BDG serum assay performed within ±5 days. Among the 69 episodes that occurred in HIV-positive patients and the 609 episodes that occurred in immunocompromised HIV-negative patients, we find an equivalent sensitivity of BDG assays compared with molecular methods to diagnose probable/proven PjP, in a first-line strategy. Furthermore, BDG assay can be used confidently to distinguish between infected and colonized patients using a 80 pg/mL cut-off. Finally, it is necessary to search for causes of false positivity to increase BDG assay performance. BDG assay represents a valuable adjunctive tool to distinguish between colonization and infection. Full article

The usefulness of (1,3)-ß-d-glucan (BDG) detection for the diagnosis of intra-abdominal candidiasis and treatment monitoring is unknown. A prospective, single-center study of consecutive patients admitted to an ICU with complicated intra-abdominal infection (IAI) over a 2-year period was conducted. BDG was measured in the peritoneal fluid and serum between day 1 (D1) and D10. Patients with a positive peritoneal fluid yeast culture (YP) were compared to those with a negative yeast culture (YN). The evolution of serum BDG was compared in the two groups. Seventy patients were included (sixty-five analyzed): YP group (n = 19) and YN group (n = 46). Median peritoneal BDG concentration during surgery was 2890 pg.mL⁻¹ [IQR: 942–12,326] in the YP group vs. 1202 pg.mL⁻¹ [IQR: 317–4223] in the YN group (p = 0.13). Initial serum BDG concentration was 130 pg.mL⁻¹ [IQR: 55–259] in the YP group vs. 88 pg.mL⁻¹ [IQR: 44–296] in the YN group (p = 0.78). No difference in evolution of serum BDG concentrations was observed between the groups (p = 0.18). In conclusion, neither peritoneal BDG nor serum BDG appear to be good discriminating markers for the diagnosis of yeast IAI. In addition, monitoring the evolution of serum BDG in yeast IAI did not appear to be of any diagnostic value. Full article

Ibrexafungerp is a new orally-available 1,3-β-D-glucan synthesis inhibitor in clinical development. Its in vitro activity and that of amphotericin B, voriconazole, and micafungin were evaluated against a collection of 168 clinical isolates of Aspergillus spp., including azole–susceptible and azole–resistant (Cyp51A mutants) Aspergillus fumigatus sensu stricto (s.s.) and cryptic species of Aspergillus belonging to six species complexes showing different patterns of antifungal resistance, using EUCAST and CLSI antifungal susceptibility testing reference methods. Ibrexafungerp displayed low geometric means of minimal effective concentrations (MECs) against A. fumigatus s.s. strains, both azole susceptible (0.040 mg/L by EUCAST and CLSI versus 1.231 mg/L and 0.660 mg/L for voriconazole, respectively) and azole resistant (0.092 mg/L and 0.056 mg/L, EUCAST and CLSI, while those for voriconazole were 2.144 mg/L and 2.000 mg/L). Ibrexafungerp was active against most of the cryptic species of Aspergillus tested, yielding MEC values only comparable to those of micafungin. Nevertheless, this new compound exhibited a moderate activity against A. ustus complex species, MECs ≥ 0.5 mg/L against Aspergillus insuetus and Aspergillus keveii strains, and was inactive against the Aspergillus alliaceus isolates tested (MEC₉₀s ≥ 16 mg/L). All in all, ibrexafungerp shows encouraging in vitro results against cryptic species of Aspergillus and azole–susceptible and azole resistant strains of A. fumigatus, some of which are difficult to treat using the available therapeutic options. Full article

Intranasal vaccination elicits secretory IgA (SIgA) antibodies in the airways, which is required for cross-protection against influenza. To enhance the breadth of immunity induced by a killed swine influenza virus antigen (KAg) or conserved T cell and B cell peptides, we adsorbed the antigens together with the TLR3 agonist poly(I:C) electrostatically onto cationic alpha-D-glucan nanoparticles (Nano-11) resulting in Nano-11-KAg-poly(I:C) and Nano-11-peptides-poly(I:C) vaccines. In vitro, increased TNF-α and IL-1ß cytokine mRNA expression was observed in Nano-11-KAg-poly(I:C)-treated porcine monocyte-derived dendritic cells. Nano-11-KAg-poly(I:C), but not Nano-11-peptides-poly(I:C), delivered intranasally in pigs induced high levels of cross-reactive virus-specific SIgA antibodies secretion in the nasal passage and lungs compared to a multivalent commercial influenza virus vaccine administered intramuscularly. The commercial and Nano-11-KAg-poly(I:C) vaccinations increased the frequency of IFNγ secreting T cells. The poly(I:C) adjuvanted Nano-11-based vaccines increased various cytokine mRNA expressions in lymph nodes compared to the commercial vaccine. In addition, Nano-11-KAg-poly(I:C) vaccine elicited high levels of virus neutralizing antibodies in bronchoalveolar lavage fluid. Microscopic lung lesions and challenge virus load were partially reduced in poly(I:C) adjuvanted Nano-11 and commercial influenza vaccinates. In conclusion, compared to our earlier study with Nano-11-KAg vaccine, addition of poly(I:C) to the formulation improved cross-protective antibody and cytokine response. Full article