epiglucan and Candidemia

Patients with C. difficile infection (CDI) experience intestinal microflora changes that can promote the overgrowth and subsequent translocation of gut resident pathogens into the blood. Consistently, CDI due to PCR-ribotype 027 strain, severe or relapsing CDI, and treatment with high-dosage vancomycin are independent risk factors for candidemia.. We review the role played by the gut microbiota during CDI and its treatment, as well as the clinical profile of CDI patients who are at risk of developing candidemia. Also, we discuss the management of these patients by focusing on pre-emptive strategies aimed at reducing the risk of candidemia, and on innovative anti-C. difficile therapies that may mitigate CDI-related effects such as the altered gut microbiota composition and prolonged intestinal mucosa damage. Expert commentary: A closer clinical and diagnostic monitoring of patients with CDI should help to limit the CDI-associated long-term consequences, including Candida infections, which worsen the outcome of hospitalized patients.

Topics: Anti-Bacterial Agents; Antifungal Agents; beta-Glucans; Candidemia; Clostridioides difficile; Enterocolitis, Pseudomembranous; Humans; Intestinal Mucosa; Microbiota; Nystatin; Risk Factors

Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1→3)-β-D-glucan (BDG) shows promise as an early biomarker of invasive fungal infection and may be useful in identifying patients who would benefit from early antifungal treatment. To date, no consistent early treatment strategy has evolved. Proof-of-concept studies are needed to assess the role of pre-emptive and empirical therapy in ICU patients and the relevance of BDG as an early marker of infection.

Topics: Adult; Antifungal Agents; beta-Glucans; Biomarkers; Candidemia; Early Diagnosis; Humans; Proteoglycans

(1,3)-β-D-glucan (BG) is a biomarker for invasive candidiasis (IC). The usefulness of BG level as a prognostic marker of treatment outcome is not well characterized.. Two hundred fifty-seven patients with proven IC were enrolled in an anidulafungin study. Clinical and microbiological responses at the end of therapy were evaluated. Serial serum BG was measured. Correlation of initial and final BG levels with overall outcome was assessed in each patient.. Two hundred three patients had at least 2 BG levels and outcomes assessed. The majority of IC was caused by non-Candida albicans (53%) and found in the blood (84%). Overall, treatment success was 85%. In successfully treated patients, the mean ± SD initial and final BG were 573 ± 681 pg/mL and 499 ± 635 pg/mL (P = .03), respectively; while in treatment-failure patients, the levels were 1224 ± 1585 pg/mL and 1293 ± 1283 pg/mL (P = .29), respectively. A negative slope in BG levels correlated with a successful treatment outcome with a positive predictive value (PPV) of 90%, and a positive slope in BG levels correlated with treatment failure with a negative predictive value (NPV) of 90%. The cutoff value for initial BG <416 pg/mL has potential to predict treatment success with a PPV of 89%.. A decrease in BG levels during therapy is associated with treatment success. An initial BG of <416 pg/mL has potential to predict successful treatment outcomes. Baseline and consecutive serum BG measurements may be useful as prognostic markers of treatment outcome in patients with IC receiving primarily echinocandin therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; beta-Glucans; Biomarkers; Candidemia; Candidiasis, Invasive; Echinocandins; Female; Humans; Male; Middle Aged; Proteoglycans; ROC Curve; Treatment Outcome

The sensitivity of the (1-3)-β-D-glucan (BDG) diagnostic test for candidemia varies in different clinical settings, and its usefulness in early diagnosis of candidemia is suboptimal. We evaluated the sensitivity of the test for early candidemia prediction. All adult patients with culture-proven candidemia who underwent a serum Goldstream Fungus (1-3)-β-D-Glucan Test within seven days prior to candidemia onset at a tertiary referral hospital between January 2017 and May 2021 were included. Any-positive BDG results within seven days prior to candidemia onset were obtained in 38 out of 93 (40.9%) patients. The positive rate increased when the test was performed near the day of candidemia onset (

Topics: Adult; beta-Glucans; Candida; Candidemia; Candidiasis; Humans; Sensitivity and Specificity

Topics: Adult; Antigens, Fungal; beta-Glucans; Biomarkers; Candidemia; Glucans; Humans; Mannans; Prospective Studies; Recurrence; Sensitivity and Specificity

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

Fungal biomarkers support early diagnosis of invasive fungal infections. In this study, we evaluated the impact of a recent update to the manufacturer-recommended cut-off for beta-1,3-D-glucan (BDG) testing (Fujifilm Wako BDG assay) on sensitivity and specificity for the detection of candidemia. Additionally, we compared the performance with tests for Candida antigen (Ag by Serion ELISA antigen Candida, Virion\\Serion) and anti-mannan antibodies (Ab by Hemkit Candida IHA, Ravo Diagnostika).. Sera of 82 patients with candidemia, which were sampled with a maximum distance of ±14 days from the date of sampling of the corresponding positive blood cultures, were retrospectively analysed for BDG, Ag and Ab. Results of BDG testing were compared with results from sera of 129 patients with candidemia from a different hospital.. Sensitivity of BDG testing (47%) was higher than for Ag (17%) or Ab (20%). By combining Ag and Ab testing, sensitivity was raised to 32%. Lowering the cut-off of BDG from 11 pg/ml to the newly recommended cut-off of 7 pg/ml resulted in a significant increase in sensitivity (47% vs 58%, p = .01 and 63% vs 71% p < .01). At both centres, the increase was significant in NAC but not in C. albicans candidemia. No significant effects on specificity were observed.. BDG testing outperformed Ag and Ab testing and its combination. Lowering the BDG cut-off had no significant impact on specificity. The increase in sensitivity can be mainly attributed to a gain in sensitivity for non-albicans Candida species bloodstream infections.

Topics: beta-Glucans; Candida; Candida albicans; Candidemia; Glucans; Humans; Proteoglycans; Retrospective Studies; Sensitivity and Specificity

Serum (1,3)-beta-d-glucan (BDG) assay is a non-culture-based test recommended for the diagnosis of invasive candidiasis owing to its faster results and higher sensitivity than blood cultures. Its performance might vary for different Candida species. The aim of this study was to determine in vitro levels of BDG in Candida auris culture supernatants and evaluate BDG levels in patients with C. auris candidemia sustained by these stains.. C. auris strains were collected from blood cultures of patients who had a concomitant (-24 to +72 hours) serum BDG test (Fungitell assay). Supernatants of broth media culture of C. auris strains and two Candida albicans (controls) strains were prepared and tested for BDG.. Ten C auris strains were included. Supernatants of two C. albicans considered as controls had a mean BDG level of 1155 pg/mL (considered 100% reactivity). The median BDG level in supernatants of C. auris strains was 275 pg/mL (IQR 165-523 pg/mL), with a median reactivity of 24% (range 6%-72%). In vivo, the median BDG level was 129 pg/mL (IQR, 28-199 pg/mL). Sensitivity of BDG for C. auris candidemia was 60%. All patients received antifungal treatment with an echinocandin initiated a median of 2 days (IQR -8 to 0) before blood collection for BDG.. Our C. auris strains released lower amounts of BDG when compared to C. albicans. Clinical implications include lower sensitivity of serum BDG for the diagnosis of C. auris candidemia with a consequent impact on management protocols in settings with high prevalence of this species.

Topics: Antifungal Agents; beta-Glucans; Candida auris; Candidemia; Candidiasis, Invasive; Glucans; Humans; Sensitivity and Specificity

Candidemia causes high mortality and is occuring at increasing rate in intensive care units (ICUs). (1,3)- β-D-glucan (BDG) testing is recommended in neutropenic patients. However the usefulness of BDG in ICUs is unclear.. This study was conducted to compare the diagnostic value of Candida score (CS), colonization index (CI), serum BDG detection, and routine laboratory parameters in ICU patients. Characteristics and laboratory data of 83 patients (15 patients with candidemia and 68 patients without candidemia) were evaluated.. Median serum BDG was significantly higher in the candidemia group (129 pg/mL vs. 36 pg/mL, p < 0.001). BDG assay with standard cut-off value ≥ of 80 pg/mL had 93.33% sensitivity and 64.18% specificity (Areas under the ROC curve (AUC): 0.788). This study concluded that the optimal cut-off value for BDG assay was 112 pg/mL with sensitivity of 86.67% and specificity of 82.09% (AUC: 0.844). C-reactive protein (CRP) with optimal cut-off value ≥ 85 mg/L and BDG ≥ 80 pg/mL had the highest AUC (0.862, 95% CI: 0.768 - 0.928) with sensitivity 93.33% and specificity 79.1%.. Predicting candidemia is essential in critically ill patients who are at high risk and have high mortality rates. The results of this study suggest that BDG testing is useful for predicting candidemia in ICU. However, BDG combined with CRP may be a stronger predictor for candidemia.

Topics: beta-Glucans; C-Reactive Protein; Candida; Candidemia; Humans; Proteoglycans; Sensitivity and Specificity

To compare serum β-D-glucan (BDG) levels in candidaemia with different Candida species, especially C. auris.. Aga Khan University clinical laboratory database was retrospectively reviewed from January 2015 to December 2019. Blood culture positive cases with any Candida species and concomitant BDG level were included.. Among the 192 cases included in our study, 48 were C. albicans, 54 C. auris, eight C. glabrata, 32 C. parapsilosis, 43 C. tropicalis and seven other Candida species. The level of BDG was significantly lower in C. auris (median 62.43, interquartile range (IQR) 12.80-182.94 pg/mL) compared to C. albicans (median 266.83, IQR 66.29-523.43 pg/mL) and C. tropicalis (median 324.41, IQR 105.20-523.44 pg/mL). The sensitivity of serum BDG was significantly lower for C. auris (43.75%, 95% CI 29.5-58.8%) than C. tropicalis (79.07%, 95% CI 64.0-90.0%).. Serum BDG has lower sensitivity in patients with suspected C. auris candidaemia in our setting. Considering that C. auris has higher morbidity and mortality than other species, a more sensitive test is required.

Topics: Antifungal Agents; beta-Glucans; Candida; Candida albicans; Candida auris; Candida tropicalis; Candidemia; Humans; Laboratories, Clinical; Pakistan; Retrospective Studies

Topics: Adult; beta-Glucans; Candidemia; Glucans; Humans; Prognosis; Proteoglycans; Tertiary Care Centers

The clinical relevance and the potential prognostic role of persistently negative (1,3)-β-D-glucan (BDG) in adults with proven candidemia is unknown.. This retrospective study included all adults diagnosed with candidemia our tertiary university hospital from 2012-2017 who had at least 2 serum BDG determinations throughout the episode of fungemia (Fungitell Assay; positive cut-off ≥80pg/mL). Epidemiology and clinical outcomes were compared between patients with all negative versus any positive BDG tests. Poor clinical outcomes included complications due to candidemia or 30-day all-cause mortality.. Overall, 26/148 (17.6%) candidemic adults had persistently negative BDG tests. These patients were less likely to present Candida growth in all 3 sets of blood cultures (15.4% vs 45.1%; P = .005) and had less severe clinical presentations (median Pitt score, 0 [interquartile range {IQR} 0-1] vs 1 [IQR 0-2] in patients with any positive BDG test; P = .039). Although adequate treatment was equally provided to both groups (96.2% in persistently negative group vs 93.4 in positive group; P = .599), the persistently negative group had a higher rate of microbiological clearance in the first follow-up blood cultures (92.3% vs 69.7% in positive group; P = .005), fewer complications due to candidemia (7.7% vs 33.6% in positive group; P = .008), a lower 30-day mortality rate (3.8% vs 23.8% in positive group; P = .004), and a shorter in-hospital stay (34 days [IQR 18-55] vs 51 days [IQR 35-91] in positive group; P = .003). In the multivariate analysis, persistently negative BDG tests were independently associated with better prognoses (odds ratio 0.12, 95% confidence interval 0.03-0.49; P = .003).. Candidemic patients with persistently negative BDG tests present a better prognosis than the comparative group, probably due to a lower systemic fungal burden. In this context, the appropriate use of persistently negative BDG results could be an aid to individualize therapeutic management in the near future.

Topics: Adult; beta-Glucans; Candidemia; Glucans; Humans; Prognosis; Proteoglycans; Retrospective Studies; Sensitivity and Specificity; Tertiary Care Centers

Topics: Adult; beta-Glucans; Blood Culture; Candida; Candidemia; DNA, Fungal; Humans; Infant, Newborn; Intensive Care Units; Intensive Care Units, Neonatal; Retrospective Studies; Sensitivity and Specificity; South Africa

Asymptom of invasive candidiasis (IC) and low positive rate of blood culture lead to delay diagnose of neonatal infection. Serum (1,3)-β-D-glucan (BDG) performs well in adult IC, but its use in neonatal IC is unclear. We evaluated the use of BDG, procalcitonin (PCT), high-sensitive C-reactive protein (hsCRP) or platelet count (PC) in neonatal IC.. We collected the data of neonates admitted to our institute. Eighty neonates were enrolled, and divided into IC group, bacterial infection (BI) group and control (CTRL) group. We analyzed the difference of these indicators between groups, and generated Receiver operator characteristic (ROC) curve. The value of BDG in antifungal therapy efficacy assessment was also investigated.. The BDG level was higher in IC group compared with BI and CTRL group. C. albicans lead to significant increase of BDG compared with C. parapsilosis. IC group had highest hsCRP level and lowest PC. PCT level was similar between groups. ROC showed that BDG or hsCRP performs well in neonatal IC, the optimal cut-off for BDG was 13.69 mg/ml. Combined BDG with hsCRP, PCT and PC increased diagnostic value. Serum BDG level was decreased during antifungal treatment.. Serum BDG performs well in identification of neonatal IC and in monitoring the antifungal therapy efficacy.

Topics: Adult; Antifungal Agents; beta-Glucans; Biomarkers; C-Reactive Protein; Candida albicans; Candida parapsilosis; Candidemia; Candidiasis, Invasive; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Pregnancy; Proteoglycans; Retrospective Studies; ROC Curve; Species Specificity; Treatment Outcome

We review the performance of culture-independent diagnostic tests (CIDTs), including β-D-glucan (BDG), polymerase chain reaction (PCR) and T2Candida, in diagnosing invasive candidiasis, their potential roles in patient management, and unintended consequences of testing.. In a recent multicenter trial, T2Candida was 90% sensitive and 98% specific for diagnosing candidemia. A new study provided the first data for T2Candida in diagnosing deep-seated candidiasis, demonstrating sensitivity/specificity of 45%/96%. Two studies showed that ongoing T2Candida-positivity is associated with poor prognosis. In several studies, serum BDG and T2Candida, targeted to patients at-risk for invasive candidiasis, were useful in guiding treatment decisions and antifungal stewardship. A randomized, multicenter trial of BDG-guided empiric antifungal treatment is underway among critically ill patients. PCR performance was highly variable for candidemia and deep-seated candidiasis in recent studies. CIDT results may overstate bloodstream infections, according to current National Healthcare Safety Network (NHSN) definitions.. BDG and T2Candida are nearing prime-time status in the clinic. To be useful, testing must be directed to carefully chosen patients and specific clinical questions. Candida PCR is limited by a need for standardized methodologies and commercial assays. NHSN definitions of bloodstream infections must be revised in the era of CIDTs.

Topics: beta-Glucans; Candida; Candidemia; Candidiasis, Invasive; Humans; Microbiological Techniques; Molecular Diagnostic Techniques; Polymerase Chain Reaction; Sensitivity and Specificity

Although the serum 1,3-β-D-glucan test has been used as an early diagnostic marker of candidemia, there are few studies regarding the association of serum 1,3-β-D-glucan levels with candidemia in severe burn patients. The purpose of this study was to elucidate the clinical significance of 1,3-β-D-glucan for the diagnosis of candidemia in severe burn patients. Data from 51 severe burn patients whose serum levels of 1,3-β-D-glucan had been measured for the suspicion of invasive fungal infection were analyzed retrospectively. The primary outcome in this study was the detection of candidemia. The levels of 1,3-β-D-glucan (pg/ml) in candidemia and noncandidemia groups ranged from 41.1 to 600.0 with a median of 90.6 and from 5.0 to 41.3 with a median of 6.8, respectively. A significant difference in the levels of 1,3-β-D-glucan was observed between the two groups. The optimal cutoff value was 40 pg/ml, with a sensitivity of 100% and a specificity of 95%, whereas the conventional cutoff value (11 pg/ml) resulted in a sensitivity of 100% and a specificity of 68%. The 1,3-β-D-glucan test was found to be useful for detecting candidemia in severe burn patients, and the cutoff value might be set to 40 pg/ml to detect it more accurately.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Burns; Candidemia; Child; Female; Humans; Male; Middle Aged; Retrospective Studies; Sensitivity and Specificity

Desirability of outcome ranking (DOOR) has been developed for assessing desirability of outcome in interventional studies. However, its possible use in observational studies of the diagnosis and early treatment of infectious diseases has not been explored so far, and it might introduce interesting features in specific scenarios. This was a post hoc analysis of a prospective observational study in intensive care unit patients with sepsis and at risk of candidemia. The probabilities that a randomly selected patient would have a more, less, and equally cost-effective early therapeutic choice following a BDG-based diagnostic strategy rather than the empirical administration of antifungals to all patients were calculated using DOOR methods. The probability of a more cost-effective therapeutic choice following the BDG-based rather than the empirical strategy was 67.81% (95% CI 67.32-68.30), whereas the probabilities of a less and equally cost-effective early therapeutic choice were 19.68% (95% CI 19.27-20.10) and 12.50% (95% CI 12.16-12.85), respectively. The application of DOOR methods to observational studies focused on diagnosis and early treatment is a novel field that could merit further investigation.

Topics: Antifungal Agents; Antigens, Fungal; beta-Glucans; Candidemia; Cost-Benefit Analysis; Disease Management; Fungi; Humans; Intensive Care Units; Prospective Studies; Sepsis; Treatment Outcome

T2 Magnetic Resonance Candida Panel (T2MR) detects Candida directly in blood. Rapid turnaround time and high negative predictive value make it a useful diagnostic test to support antifungal discontinuation. This retrospective quasi-experiment compared empiric anidulafungin days of therapy (DOTs) in intensive care unit (ICU) patients with suspected candidemia that had negative blood cultures and negative 1,3-β-D-glucan (BDG) versus negative blood cultures and negative T2MR. In 206 ICU patients, median anidulafungin DOTs were 2 (1, 5) compared to 1 (1, 2), respectively (P < 0.001); T2MR was associated with early discontinuation, AdjOR 3.0 95% CI (1.7-5.6), P < 0.001. Proven candidemia after discontinuation of anidulafungin occurred in 3% of BDG and 2% of T2MR patients at a median of 8 and 21 days, respectively. T2MR testing supports safe, early discontinuation of empiric antifungal therapy in ICU patients with suspected candidemia. Prospective studies to better define the role of T2MR in antifungal stewardship are warranted.

Topics: Aged; Antifungal Agents; beta-Glucans; Blood Culture; Candida; Candidemia; Drug Monitoring; Female; Humans; Intensive Care Units; Magnetic Resonance Spectroscopy; Male; Middle Aged; Retrospective Studies

Although treatment for candidaemia is time critical, culture-based tests prolong turnaround times and may promote underdiagnosis. Non-culture-based tests have the potential to overcome these difficulties but are in limited clinical use. The aim of this work was to undertake an initial evaluation of two non-culture-based tests for diagnosis of candidaemia.. Patients with candidaemia were identified prospectively over a 4-month period. Sera drawn from case (candidaemic) and control (non-candidaemic) patients on the same day as the positive blood culture were tested with both the Renishaw RenDx Fungiplex test and a commercial β-d-glucan (BDG) assay (Fungitell, Associates of Cape Cod). Sensitivity and specificity were calculated independently and in combination, using paired blood culture as the reference standard.. There were 10 eligible case patients and 39 negative controls. PCR sensitivity and specificity were found to be 44.4% (95% CI 18.9% to 73.3%) and 87.2% (72.8% to 94.8%), respectively. BDG sensitivity and specificity were 80% (47.9% to 95.4%) and 89.7% (75.9% to 96.5%), respectively. When combining PCR and BDG, sensitivity was 90% (95% CI 57.4% to 100%) and specificity was 79.5% (64.2% to 89.5%). When two sequential specimens were tested, PCR sensitivity increased to 60% (95% CI 31.2% to 83.3%) and BDG sensitivity to 90% (54.7% to 100%).. A combination of tests, or a single test at multiple time points, may be preferable to relying on one test at a single time point. This should be accounted for in design of future diagnostic accuracy studies of tests for invasive candidosis.

Topics: Aged; beta-Glucans; Biomarkers; Candida; Candida albicans; Candida glabrata; Candida parapsilosis; Candidemia; Case-Control Studies; DNA, Fungal; Female; Humans; Male; Microbiological Techniques; Middle Aged; Polymerase Chain Reaction; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Time Factors

Definitive diagnosis of invasive candidiasis (IC) may be difficult to achieve in patients with haematological malignancy (PHM). We aimed to evaluate the performance of BDG for the diagnosis and the follow-up of IC in PHM.. We retrospectively reviewed the serological data of BDG assay in adult and paediatric PHM, who developed candidemia or chronic disseminated candidiasis (CDC) through a 4-year period. Sensitivity and kinetics of BDG were determined for both clinical forms.. In a panel of 3027 PHM, incidence rates of candidemia and CDC ranged between 0.74 and 0.77 and 0.30 and 0.44 according to the group of patients. At the time of diagnosis, 43.5% and 73% of cases of candidemia and CDC had a positive BDG assay, respectively. We found a significant correlation between the level of BDG at diagnosis and the outcome of candidemia (p = 0.022). In all cases of CDC, BDG negative results were obtained 2 to 6 months before recovery of the CT-scan lesions.. BDG exhibits a low sensitivity to detect IC in PHM, but its kinetics correlates the clinical outcome. Additional studies are warranted in patients with CDC to evaluate the interest of monitoring BDG levels to anticipate the discontinuation of antifungal maintenance therapy.

Topics: Aged; Antibodies, Fungal; Antifungal Agents; beta-Glucans; Candida; Candidemia; Candidiasis; Candidiasis, Invasive; Follow-Up Studies; Hematologic Neoplasms; Humans; Intensive Care Units; Kinetics; Middle Aged; Retrospective Studies; Sensitivity and Specificity

Diagnosis of complicated candidaemia represents a challenge for clinicians since early clinical manifestations may be non-specific and difficult to identify, thus precluding an appropriate treatment.. This was a multicentre prospective study for predicting complicated episodes in patients with bloodstream infection caused by Candida species, while assessing the value of follow-up blood cultures (BCs) and the persistence of positive results for T2Candida MR (T2MR) and blood β-d-glucan (BDG) tests. Immediately after the first positive BC yielding Candida species, samples were obtained on days 0, +2, +4, +7 and +14, to simultaneously perform follow-up BC, T2MR and BDG. An episode of candidaemia was defined as 'complicated' when (i) it caused septic metastasis; and/or (ii) it was the cause of the patient's death.. From January to June 2017, 30 patients were enrolled in the study. Of these, nine (30%) had complicated candidaemia. Values of persistently positive samples for the prediction of complicated episodes for BCs, T2MR and BDG, respectively, were as follows: sensitivity (44.4%, 100%, 100%); specificity (76.1%, 76.1%, 38.9%); positive predictive value (PPV) (44.4%, 64.2%, 40.9%) and negative predictive value (NPV) (76.1%, 100%, 100%). In multivariate analysis, having a positive T2MR within the first 5 days was associated with an almost 37-fold higher risk of developing complicated candidaemia.. The T2MR test performed in patients with proven candidaemia may be a better marker of complicated infection than follow-up BCs or BDG. It is possible that this test may change current clinical practice, influencing the length and type of antifungal therapy in this population.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Blood Culture; Candidemia; Early Diagnosis; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prognosis; Prospective Studies; Sensitivity and Specificity

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

While Candida pneumonia is life-threatening, biomarker measurements to early detect suspected Candida pneumonia are lacking. This study compared the diagnostic values of measuring levels of (1, 3)-β-D-glucan in endotracheal aspirate, bronchoalveolar lavage fluid, and serum to detect suspected Candida pneumonia in immunocompromised and critically ill patients.. This prospective, observational study enrolled immunocompromised, critically ill, and ventilated patients with suspected fungal pneumonia in mixed intensive care units from November 2010 to October 2011. Patients with D-glucan confounding factors or other fungal infection were excluded. Endotracheal aspirate, bronchoalveolar lavage fluid and serum were collected from each patient to perform a fungal smear, culture, and D-glucan assay.. After screening 166 patients, 31 patients completed the study and were categorized into non-Candida pneumonia/non-candidemia (n = 18), suspected Candida pneumonia (n = 9), and non-Candida pneumonia/candidemia groups (n = 4). D-glucan levels in endotracheal aspirate or bronchoalveolar lavage were highest in suspected Candida pneumonia, while the serum D-glucan level was highest in non-Candida pneumonia/candidemia. In all patients, the D-glucan value in endotracheal aspirate was positively correlated with that in bronchoalveolar lavage fluid. For the detection of suspected Candida pneumonia, the predictive performance (sensitivity/specificity/D-glucan cutoff [pg/ml]) of D-glucan in endotracheal aspirate and bronchoalveolar lavage fluid was 67%/82%/120 and 89%/86%/130, respectively, accounting for areas under the receiver operating characteristic curve of 0.833 and 0.939 (both P < 0.05), respectively. Measuring serum D-glucan was of no diagnostic value (area under curve =0.510, P = 0.931) for the detection of suspected Candida pneumonia in the absence of concurrent candidemia.. D-glucan levels in both endotracheal aspirate and bronchoalveolar lavage, but not in serum, provide good diagnostic values to detect suspected Candida pneumonia and to serve as potential biomarkers for early detection in this patient population.

Topics: Adult; Aged; beta-Glucans; Biomarkers; Bronchoalveolar Lavage Fluid; Candidemia; Candidiasis; Critical Illness; Early Diagnosis; Female; Humans; Immunocompromised Host; Intensive Care Units; Male; Middle Aged; Pneumonia; Prospective Studies; Proteoglycans; Sensitivity and Specificity

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

β-D-glucan (Fungitell) and polymerase chain reaction-based (T2Candida) assays of blood samples are FDA-approved adjuncts to cultures for diagnosing candidemia and other types of invasive candidiasis, but their clinical roles are unclear. In this chapter, we describe laboratory protocols for performing Fungitell and T2Candida assays. We then discuss step-by-step methods for interpreting test results at the bedside using a Bayesian framework, and for incorporating assays into rational patient management strategies. Prior to interpreting results, clinicians must recognize that test performance varies based on the type of invasive candidiasis being diagnosed. In general, the type of invasive candidiasis that is most likely in a given patient can be identified, and the pretest likelihood of disease estimated. From there, positive and negative predictive values (PPV, NPV) for an assay can be calculated. At a population level, tests can be incorporated into screening strategies for antifungal treatment. NPV and PPV thresholds can be defined for discontinuing antifungal prophylaxis or initiating preemptive treatment, respectively. Using the thresholds, it is possible to assign windows of pretest likelihood for invasive candidiasis (and corresponding patient populations) in which tests are most likely to valuable. At the individual patient level, tests may be useful outside of the windows proposed for screening populations. The interpretive and clinical decision-making processes we discuss will be applicable to other diagnostic assays as they enter the clinic, and to existing assays as more data emerge from various populations.

Topics: beta-Glucans; Candida; Candidemia; Clinical Decision-Making; Diagnostic Techniques and Procedures; Humans; Reagent Kits, Diagnostic; Reproducibility of Results

Topics: beta-Glucans; Candidemia; Humans; Prognosis; Proteoglycans; Serum; Survival Analysis

Topics: beta-Glucans; Candidemia; Humans; Prognosis; Proteoglycans; Serum; Survival Analysis

The aim of this study was to evaluate the sensitivity and the levels of 1,3-β-d-glucan (BDG) among patients with candidaemia due to different Candida species. Retrospective study of all patients who had a single-species candidaemia and BDG testing performed within 48 h from the onset of candidaemia during 2009-2015 was performed. Factors influencing the sensitivity of BDG, including the presence of a central venous catheter, antifungal therapy and Candida species, were analysed in univariate and multivariate models. In all, 107 patients with the following Candida distribution were included: 46 (43%) Candida albicans, 37 (35%) Candida parapsilosis, and 24 (22%) other species. BDG sensitivity and levels were the highest in C. albicans candidaemia and lowest for C. parapsilosis (respectively, 72% and 410 pg/mL for C. albicans, 41% and 39 pg/mL for C. parapsilosis, and 63% and 149 pg/mL for other species; p 0.015 and p 0.003). In multivariate analysis, Candida species (parapsilosis versus others) was the only factor influencing the sensitivity of BDG (OR 0.3, 95% CI 0.1-0.7, p 0.006). The sensitivity of BDG in candidaemia seems highly dependent on the fungal species, with the lowest being for C. parapsilosis.

Topics: Aged; Aged, 80 and over; beta-Glucans; Candida; Candidemia; Diagnostic Tests, Routine; Female; Humans; Male; Middle Aged; Proteoglycans; Retrospective Studies; Sensitivity and Specificity; Serum

Empirical antifungal therapy in high-risk ICU patients is an attractive strategy, but overuse of antifungal agents is a potential problem.. We evaluated if ICU patients at high risk to develop candidaemia identified by a prediction rule could discontinue empirical antifungal therapy on the basis of repeatedly negative 1-3-β-d-glucan (BDG) tests.. We conducted a multicentre cohort study in 85 ICU patients receiving antibiotics or with central venous catheter plus two additional factors (dialysis, parenteral nutrition, surgery, pancreatitis or receipt of corticosteroids or other immunosuppressive agents) plus either fever, hypothermia, hypotension, acidosis, elevated C-reactive protein or leucocytosis. Blood cultures (days 1 and 2) and BDG (days 1-3, baseline period) were performed and anidulafungin was given. On day 4, patients with negative blood cultures and BDG discontinued antifungal therapy. Registered in ClinicalTrials.gov (NCT01734525).. The incidence of candidaemia was 8.2% in patients selected versus 0.5% in patients without entry criteria (16.9 times higher). Sixty-four patients (75.3%) had baseline positive BDG, including 7 with candidaemia. All 21 patients with baseline negative BDG discontinued anidulafungin on day 4. None developed candidaemia until day 30.. Early discontinuation of empirical echinocandin therapy in high-risk ICU patients based on consecutive negative BDG tests may be a reasonable strategy, with great potential to reduce the overuse of echinocandins in ICU patients. Prospective studies with a higher number of patients are needed.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Candidemia; Cohort Studies; Drug Monitoring; Echinocandins; Female; Humans; Intensive Care Units; Male; Middle Aged; Pilot Projects; Prospective Studies; Proteoglycans; Withholding Treatment; Young Adult

A retrospective study was conducted to assess the role of initial serum (1,3)-β-d-glucan (BDG) values in predicting mortality in proven candidaemia. The study was conducted in two large teaching hospitals in Italy and Brazil. From January 2009 to June 2014, all patients with proven candidaemia who underwent a BDG test within 96 hours before or after the first positive blood culture were included in the study. The primary end point was 28-day mortality, with the role of initial BDG being assessed by univariate and multivariate analyses. A total of 104 patients met the inclusion criteria. Overall, the crude 28-day mortality was 30% (31/104). In the final multivariate model, an initial BDG of >287 pg/mL (odds ratio (OR) 4.40, 95% confidence interval (CI) 1.56-12.39, p 0.005), haemodialysis (OR 4.33, 95% CI 1.24-15.17, p 0.022) and a Pitt score of ≥ 2 (OR 4.10, 95% CI 1.24-13.54, p 0.021) were significant predictors of 28-day mortality. The >287 pg/mL cutoff predicted 28-day mortality with 65% sensitivity and 70% specificity. Centre of enrolment (p for interaction 0.012), haemodialysis (p for interaction 0.062) and timing of BDG test of more than 24 hours before or after the positive culture (p for interaction 0.143) appeared to interact with BDG's ability to predict mortality. Although not statistically significant, the last two of these interactions might partially explain why BDG's ability to predict mortality was present only in the Italian cohort.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Brazil; Candidemia; Decision Support Techniques; Female; Hospitals, Teaching; Humans; Italy; Male; Middle Aged; Prognosis; Proteoglycans; Retrospective Studies; Sensitivity and Specificity; Serum; Survival Analysis

The direct or indirect interactions that antifungals have with the host immune response may play a significant role in defining their activity in vivo. However, the impact that acquired antifungal resistance has on the immunopharmacologic activity of antifungals is not well described. We assessed the immunopharmacologic activity of caspofungin, micafungin, and voriconazole among isolates of Candida glabrata with or without FKS-mediated echinocandin resistance. Clinical bloodstream isolates of C. glabrata from patients who did (n = 5) or did not (n = 3) develop persistent candidemia and who did (n = 2) or did not (n = 11) harbor FKS gene mutations were included. A cell-based assay was used to compare differences in macrophage activation among isolates when grown in the presence or absence of subinhibitory concentrations of caspofungin, micafungin, or voriconazole. In the absence of antifungals, macrophage activation was significantly lower for index C. glabrata isolates obtained from persistent candidemia patients than for those from nonpersistent patients (33% versus 79% increase over negative controls, respectively; P < 0.01). Growth of isolates possessing wild-type FKS genes in subinhibitory concentrations of micafungin or caspofungin, but not voriconazole, significantly increased macrophage inflammatory responses compared to untreated controls (1.25- to 2.75-fold increase, P < 0.01). For isolates harboring the FKS2 hot spot 1 (HS1) S663P mutation, however, a significant increase was observed only with micafungin treatment (1.75-fold increase versus negative control, P < 0.01). Macrophage activation correlated with the level of unmasking of β-glucan in the cell wall. The diminished macrophage inflammatory response to isolates that caused persistent candidemia and differential immunopharmacologic activity of echinocandins among FKS mutants suggest that certain strains of C. glabrata may have a higher propensity for immunoevasion and development of antifungal resistance during treatment.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida glabrata; Candidemia; Caspofungin; Cell Line; Echinocandins; Fungal Proteins; Humans; Immunity, Innate; Lipopeptides; Micafungin; Mice; Microbial Sensitivity Tests; Mutation; Voriconazole

We evaluated a novel plasma (1,3)-β-d-glucan (BDG) detection assay for the diagnosis of candidemia in children. The median BDG levels were 73.4 pg/ml in patients with candidemia and <10 pg/ml in patients without candidemia (P < 0.001). Receiver operating characteristic analysis revealed a cutoff point of 14 pg/ml and an area under the curve of 0.802. At these values, the assay demonstrated 68% sensitivity, 91% specificity, 66% positive predictive value, and 91% negative predictive value. Plasma BDG levels were undetectable in 18 candidemia cases.

Topics: beta-Glucans; Candidemia; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Infant; Infant, Newborn; Male; Microbiological Techniques; Plasma; Predictive Value of Tests; Proteoglycans; ROC Curve; Sensitivity and Specificity

Testing for (1→3)-beta-D-glucan (BDG) is used for detection of invasive fungal infection. However, current assays lack automation and the ability to conduct rapid single-sample testing. The Fungitell assay was adopted for automation and evaluated using clinical samples from patients with culture-proven candidemia and from culture-negative controls in duplicate. A comparison with the standard assay protocol was made in order to establish analytical specifications. With the automated protocol, the analytical measuring range was 8-2500 pg/ml of BDG, and precision testing resulted in coefficients of variation that ranged from 3.0% to 5.5%. Samples from 15 patients with culture-proven candidemia and 94 culture-negative samples were evaluated. All culture-proven samples showed BDG values >80 pg/ml (mean 1247 pg/ml; range, 116-2990 pg/ml), which were considered positive. Of the 94 culture-negative samples, 92 had BDG values <60 pg/ml (mean, 28 pg/ml), which were considered to be negative, and 2 samples were false-positive (≥80 pg/ml; up to 124 pg/ml). Results could be obtained within 45 min and showed excellent agreement with results obtained with the standard assay protocol. The automated Fungitell assay proved to be reliable and rapid for diagnosis of candidemia. It was demonstrated to be feasible and cost efficient for both single-sample and large-scale testing of serum BDG. Its 1-h time-to-result will allow better support for clinicians in the management of antifungal therapy.

Topics: Antigens, Fungal; Automation, Laboratory; beta-Glucans; Candida; Candidemia; Humans; Predictive Value of Tests; Reproducibility of Results; Sensitivity and Specificity; Time Factors

Prompt diagnosis of candidaemia and invasive candidosis is crucial to the early initiation of antifungal therapy. The poor sensitivity of blood cultures (BCs) has led to the development of fungal glycan tests as a diagnostic adjunct. We analysed the performance of tests for the detection of circulating β-D-1,3-glucan (BDG) and mannan in the intensive care unit (ICU) setting.. This retrospective, case-control study included 43 ICU patients with candidaemia and 67 controls, hospitalised on the same ward and assessed weekly for yeast colonisation with simultaneous serum sampling; 340 sera taken before and after positive BCs were available for the cases group and 203 for the controls. BDG and mannan levels were determined using the Fungitell® and Platelia™ Candida Ag tests, respectively.. BDG was detected early in sera from cases patients but was also present in several sera from controls. Increasing the cut-off from 80 pg/mL to 350 pg/mL and 800 pg/mL resulted in sensitivity/specificity ratios of 0.97/0.31, 0.65/0.74, 0.30/0.86, respectively. Detection of mannan was more specific but lacked sensitivity. No obvious correlation was found between BDG and colonisation, but a trend existed between high colonisation and high BDG. Candidaemia relapses were associated with a rise in BDG and mannan but, in contrast to the transient nature of mannan, BDG persisted up to 7 weeks after positive BCs.. A combination of mannan and BDG tests could be used to guide pre-emptive therapeutic decisions in ICU patients.

Topics: Aged; Antibodies; beta-Glucans; Biomarkers; Candidemia; Case-Control Studies; Cell Wall; Early Diagnosis; Female; Fungal Polysaccharides; Humans; Intensive Care Units; Male; Mannans; Middle Aged; Recurrence; Retrospective Studies; Sensitivity and Specificity

We conducted this study to identify risk factors that may predict whether Candida spp. are causative agents of suspected catheter-related bloodstream infections (CRBSIs). All patients with laboratory-confirmed CRBSIs at Kyoto University Hospital between 2009 and 2011 were included. We compared the clinical features of candidal CRBSIs (78 cases) and non-candidal CRBSIs (258 cases). According to a multivariate analysis, a solid tumor (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.75-5.53), total parental nutrition (OR, 2.65; 95% CI, 1.39-5.06), and the administration of anti-anaerobic agents (OR, 2.22; 95% CI, 1.03-4.79) were significantly more common among candidal CRBSIs. The (1,3)-β-D-glucan (BDG) test was positive among 94.6% (35/37) of candidal CRBSI patients and 9.4% (10/106) of non-candidal CRBSI cases. The administration of antifungal agents may be considered for patients with these risk factors, especially when the BDG test is positive.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Candidemia; Catheter-Related Infections; Female; Hospitals, University; Humans; Japan; Male; Middle Aged; Prospective Studies; Proteoglycans; Risk Factors

The aim of this study was to evaluate the usefulness of serum (1,3)-beta-D-glucan (BDG) for earlier detection of breakthrough candidemia. We reviewed the medical records of patients with candidemia from January 2008 to March 2013. Serum BDG was measured by Wako turbidimetric assay. During the study period, a total of 147 cases of candidemia were identified, and 31 patients met the criteria for breakthrough candidemia. Serum BDG levels were measured in 25 patients with breakthrough candidemia and 67 patients with nonbreakthrough candidemia. Almost all of the patients with breakthrough candidemia had hematological malignancies. More candidemia were caused by non-C. albicans Candida in the breakthrough group than in the nonbreakthrough group (92.0% vs. 61.8%, p = .005). The median BDG value was significantly lower in breakthrough episodes than in non-breakthrough episodes (18.5 pg/ml vs. 90.4 pg/ml, p = .01). Moreover, BDG values under the cutoff was significantly higher in patients with breakthrough candidemia than in those with nonbreakthrough candidemia (44% vs. 19%, p = .03). In summary, BDG alone was insufficient to detect breakthrough candidemia, and candidemia could occur in patients being treated with antifungal agents, even when the BDG value was under the cutoff value.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Biomarkers; Candidemia; Female; Humans; Male; Middle Aged; Proteoglycans; Young Adult

We conducted a case-control study using the Fungitell assay, the novel Platelia Candida Antigen (Ag) Plus and Candida Antibody (Ab) Plus assays, and the Cand-Tec latex agglutination test to evaluate the usefulness of (1→3)-β-D-glucan (BDG), mannan antigen with/without anti-mannan antibody, and Cand-Tec Candida antigen measurement for the diagnosis of candidemia. A total of 56 patients fulfilled the inclusion criteria and were enrolled. One hundred patients with bacteremia and 100 patients with sterile blood cultures served as negative controls. In the candidemia group, median (1→3)-β-D-glucan, mannan antigen, and anti-mannan antibody levels were 427 pg/ml, 190 pg/ml, and 18.6 antibody units (AU)/ml, respectively. All three parameters were significantly elevated in patients with candidemia. The sensitivity and specificity were, respectively, 87.5% and 85.5% for (1→3)-β-D-glucan, 58.9% and 97.5% for mannan antigen, 62.5% and 65.0% for anti-mannan antibody, 89.3% and 63.0% for mannan antigen plus anti-mannan antibody, 89.3% and 85.0% for BDG plus mannan antigen, and 13.0% and 93.9% for Cand-Tec Candida antigen. The low mannan antigen sensitivity was in part caused by Candida parapsilosis and Candida guilliermondii fungemias, which were not detected by the Platelia Candida Ag Plus assay. When the cutoff was lowered from 125 pg/ml to 50 pg/ml, mannan antigen sensitivity increased to 69.6% without severely affecting the specificity (93.5%). Contrary to recently published data, superficial candidiasis was not associated with elevated mannan antigen levels, not even after the cutoff was lowered. Combining procalcitonin (PCT) with (1→3)-β-D-glucan to increase specificity provided a limited advantage because the benefit of the combination did not outweigh the loss of sensitivity. Our results demonstrate that the Cand-Tec Candida antigen and the mannan antigen plus anti-mannan antibody measurements have unacceptably low sensitivity or specificity. Of the four tests compared, (1→3)-β-D-glucan and mannan antigen are the superior biomarkers, depending on whether a sensitivity-driven or specificity-driven approach is used.

Topics: Aged; Antibodies, Fungal; Antigens, Fungal; beta-Glucans; Biomarkers; Candidemia; Case-Control Studies; Clinical Laboratory Techniques; Female; Humans; Male; Mannans; Middle Aged; Proteoglycans; Sensitivity and Specificity; Serum

Serum (1→3)-β-D-glucan (BG) is increasingly used as diagnostic marker for invasive fungal infections. Exposure to gauze may lead to false-positive BG assays. The role of BG is unclear in thermally injured patients who frequently require extensive gauze coverage; therefore, we prospectively evaluated BG levels in burn-injured patients. Serum BG levels were measured in 18 burn patients immediately before application of the first dressing and 12 h after. Patients were stratified by extent of total body surface area (TBSA) requiring gauze coverage: <20%, 20-39%, 40-60% and >60%. BG levels were obtained from patients with non-burn trauma as controls. BG results were positive (>80 pg ml⁻¹) in 9/18 (50%) patients at baseline and in 8/18 (44%) 12 h after application of the first dressing. BG levels were positive in 1/5 (20%) of patients with <20% TBSA requiring gauze and in 10/13 (77%) with ≥ 20% (P < 0.05). None of the control patients had positive BG at any time point and none of the patients had candidemia at baseline. Mean serum BG levels decreased (19.44 pg ml⁻¹) after gauze placement. False-positive serum BG elevations are common in this patient population. Positivity correlates with extent of TBSA injured, but is not impacted by the gauze itself.

Topics: beta-Glucans; Burns; Candida; Candidemia; Female; Humans; Prospective Studies; Proteoglycans

The sensitivity of blood cultures for diagnosing invasive candidiasis (IC) is poor.. We performed a validated Candida real-time polymerase chain reaction (PCR) and the Fungitell 1,3-β-D-glucan (BDG) assay on blood samples collected from prospectively identified patients with IC (n = 55) and hospitalized controls (n = 73). Patients with IC had candidemia (n = 17), deep-seated candidiasis (n = 33), or both (n = 5). Controls had mucosal candidiasis (n = 5), Candida colonization (n = 48), or no known Candida colonization (n = 20).. PCR using plasma or sera was more sensitive than whole blood for diagnosing IC (P = .008). Plasma or sera PCR was more sensitive than BDG in diagnosing IC (80% vs 56%; P = .03), with comparable specificity (70% vs 73%; P = .31). The tests were similar in diagnosing candidemia (59% vs 68%; P = .77), but PCR was more sensitive for deep-seated candidiasis (89% vs 53%; P = .004). PCR and BDG were more sensitive than blood cultures among patients with deep-seated candidiasis (88% and 62% vs 17%; P = .0005 and .003, respectively). PCR and culture identified the same Candida species in 82% of patients. The sensitivity of blood cultures combined with PCR or BDG among patients with IC was 98% and 79%, respectively.. Candida PCR and, to a lesser extent, BDG testing significantly enhanced the ability of blood cultures to diagnose IC.

Topics: beta-Glucans; Candida; Candidemia; Candidiasis; Candidiasis, Invasive; DNA, Fungal; Humans; Prospective Studies; Proteoglycans; Reagent Kits, Diagnostic; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity

Ocular candidiasis is a major complication of Candida bloodstream infection (BSI). This study was performed to reveal the clinical characteristics of ocular candidiasis. Of the 220 patients with Candida BSI, 204 cases received ophthalmology consultations between January 2005 and December 2011 at 2 teaching hospitals. Fifty-four (26.5%) cases had findings consistent with the diagnosis of ocular candidiasis. Of these 54 cases, 43 (79.6%) were diagnosed within 7 days after a positive blood culture. Among ocular candidiasis cases, more cases were due to Candida albicans (P =0.034 odds ratio [OR]; 3.68 95% confidence interval [CI] 1.11-12.2) and had higher β-d-glucan values (P = 0.001 OR; 9.99 95% CI 2.60-21.3). We need to consider fundoscopic examination to be performed within the first 7 days of therapy, especially for those patients who have C. albicans BSIs and higher β-d-glucan values. Additionally, follow-up fundoscopic examination should be considered before stopping therapy for high-risk patients.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Candidemia; Candidiasis; Diagnostic Techniques, Ophthalmological; Eye Infections, Fungal; Female; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Factors

To assess the value of (1→3)-β-D: -glucan (BDG), Candida albicans germ tube antibody (CAGTA), C-reactive protein (CRP), and procalcitonin (PCT) levels for the diagnosis of invasive candidiasis (IC) and for differentiating Candida spp. colonization from infection in ICU patients with severe abdominal conditions (SAC).. Prospective study of 176 non-neutropenic patients, with SAC at ICU admission, and expected to stay at least 7 days. Surveillance cultures and BDG, CAGTA, CRP, and PCT levels were performed on the third day of ICU stay and twice a week for four consecutive weeks. Patients were grouped into invasive candidiasis (IC), Candida colonization, and neither colonized/nor infected. The classification and regression tree (CART) analysis was used to predict IC in colonized patients. The discriminatory ability of the obtained prediction rule was assessed by the area under the ROC curve (AUC).. The probabilities of IC were 59.3 % for the terminal node of BDG greater than 259 pg/mL and 30.8 % for BDG less than 259 pg/mL and CAGTA positivity, whereas there was a 93.9 % probability in predicting the absence of IC for BDG less than 259 pg/mL and negative CAGTA. Using a cutoff of 30 % for IC probability, the prediction rule showed 90.3 % sensitivity, 54.8 % specificity, 42.4 % positive predictive value, and 93.9 % negative predictive value with an AUC of 0.78 (95 % confidence interval 0.76-0.81). Significant differences in CRP (p = 0.411) and PCT (p = 0.179) among the studied groups were not found.. BDG with a positive test for CAGTA accurately differentiated Candida colonization from IC in patients with SAC, whereas CRP and PCT did not.

Topics: Aged; Antibodies, Fungal; beta-Glucans; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Candida albicans; Candidemia; Decision Trees; Digestive System Diseases; Female; Humans; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Sensitivity and Specificity

In 6 hematopoietic stem cell transplant (HSCT) recipients with candidemia, the (1,3)-β-d-glucan (BG) test was positive a median of 2.5 days after a positive blood culture. Only in 1 patient did BG positivity precede positive blood cultures. BG concentrations decreased in patients with clinical response, but positive BG results persisted long after blood cultures became sterile (median, 48 days).

Topics: Adult; beta-Glucans; Biomarkers; Candida; Candidemia; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Proteoglycans; Time Factors

This study determined the value of (1,3)-β-d-glucan (BDG), Candida mannan (MN) and Candida species-specific DNA as surrogates for diagnosis of candidaemia. Thirty-nine patients yielding Candida species in blood cultures were investigated for presence of BDG, MN and Candida species-specific DNA in serum samples. The Candida spp. bloodstream isolates included C. albicans (n = 16), C. tropicalis (n = 10), C. parapsilosis (n = 7), C. glabrata (n = 3) and C. dubliniensis (n = 3). Positivity of the three markers was as follows: Candida DNA for corresponding Candida species, 100%; BDG, 87%; MN, 59%. Despite varying sensitivities of these biomarkers, they provided a useful adjunct to the diagnosis of candidaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Candida; Candidemia; Child; Child, Preschool; DNA, Fungal; Female; Humans; Infant; Male; Mannans; Middle Aged; Mycological Typing Techniques; Polymerase Chain Reaction; Proteoglycans; Sensitivity and Specificity; Species Specificity; Young Adult

Microbiological diagnosis of nosocomial candidemia is negatively affected by suboptimal culture yield. Alternative methods are not fully reliable as an aid in candidemia diagnosis. Recently, the detection of (1,3)-β-D-glucan (BG) has been shown to be very promising in this setting. We carried out a prospective study on the clinical usefulness of BG detection in early diagnosis of candidemia. BG detection was performed in patients with fever unresponsive to antibacterial agents and risk factors for candidemia. BG detection was done with the Fungitell test. A total of 152 patients were included in the study; 53 were proven to have candidemia, while in 52 patients candidemia was excluded on microbiological and clinical bases. The remaining 47 patients were considered to have possible candidemia. In summary, 41 of 53 candidemia patients (77.3%), 9 of 52 patients without candidemia (17.3%), and 38 of 47 patients with possible candidemia (80.8%) were positive in the BG assay. With these results, the sensitivity and the specificity of the assay were 77% and 83%, respectively. BG levels of >160 pg/ml were highly predictive of candidemia. In 36 of 41 patients with candidemia and positive BG testing, the BG assay was performed within 48 h from when the first Candida-positive blood sample for culture was drawn, thus allowing a possible earlier start of antifungal therapy. Based on these results, the BG assay may be used as an aid in the diagnosis of nosocomial candidemia. The timing of assay performance is critical for collecting clinically useful information. However, the test results should be associated with clinical data.

Topics: Antigens, Fungal; beta-Glucans; Candidemia; Clinical Laboratory Techniques; Cross Infection; Early Diagnosis; Humans; Immunoassay; Prospective Studies; Sensitivity and Specificity

Fungal sepsis is one of the major problems in neonatal and pediatric care unit settings. The availability of new diagnostic techniques could allow medical practitioners to rapidly identify septic patients and to improve their outcome. The aim of this study was to evaluate the performance of the 1→3-β-d-glucan (BDG), individually and in comparison with the Candida mannan (CM) antigen, in ten preterm infants and five onco-haematological pediatric patients with Candida bloodstream infections already proven by positive culture. The serum levels of BDG were >80 pg/mL on the same day as a positive blood culture in all examined patients, while CM antigen was negative in the patients with C. parapsilosis fungemia and in one further case due to C. albicans. These results suggest that a regular monitoring of serum circulating antigens (i.e., 1→3-β-d-glucan) combined with other microbiological and clinical information, may allow earlier and accurate diagnosis. However, further studies are necessary to confirm its usefulness in routine clinical practice.

Topics: Adolescent; Antigens, Fungal; beta-Glucans; Candida; Candida albicans; Candidemia; Child; Child, Preschool; Colorimetry; Female; Humans; Infant; Infant, Newborn; Male; Proteoglycans; Reproducibility of Results; Sensitivity and Specificity; Species Specificity

The culture-independent serum (1→3)-β-D-glucan (BG) detection test may allow early diagnosis of invasive fungal disease, but its clinical usefulness needs to be firmly established. A prospective single-center observational study was conducted to compare the diagnostic value of BG assay, Candida score (CS), and colonization index in intensive care unit (ICU) patients at risk for Candida sepsis.. Of 377 patients, consecutively admitted to ICU for sepsis, 95 patients having an ICU stay of more than five days were studied. Blood specimens for fungal culture and BG measurement were obtained at the onset of clinical sepsis. For CS and colonization index calculations, surveillance cultures for Candida growth, and/or clinical data were recorded.. Sixteen (16.8%) patients were diagnosed with proven invasive fungal infection, 14 with candidiasis (13 candidemia and 1 mediastinitis) and 2 with pulmonary aspergillosis or fusariosis. Of 14 invasive Candida-infection patients, 13 had a serum sample positive for BG, 10 had a CS value ≥ 3, and 7 a colonization index ≥ 0.5. In the 12 candidemic patients, a positive BG result was obtained 24 to 72 hrs before a culture-documented diagnosis of invasive candidiasis. The positive and negative predictive values for the BG assay were higher than those of CS and colonization index (72.2% versus 57.1% and 27.3%; and 98.7% versus 97.2% and 91.7%, respectively).. A single-point BG assay based on a blood sample drawn at the sepsis onset, alone or in combination with CS, may guide the decision to start antifungal therapy early in patients at risk for Candida infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Candida; Candidemia; Colony Count, Microbial; Early Diagnosis; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Sepsis; Young Adult

Invasive candidiasis is a frequent life-threatening complication in critically ill patients. Early diagnosis followed by prompt treatment aimed at improving outcome by minimizing unnecessary antifungal use remains a major challenge in the ICU setting. Timely patient selection thus plays a key role for clinically efficient and cost-effective management. Approaches combining clinical risk factors and Candida colonization data have improved our ability to identify such patients early. While the negative predictive value of scores and predicting rules is up to 95 to 99%, the positive predictive value is much lower, ranging between 10 and 60%. Accordingly, if a positive score or rule is used to guide the start of antifungal therapy, many patients may be treated unnecessarily. Candida biomarkers display higher positive predictive values; however, they lack sensitivity and are thus not able to identify all cases of invasive candidiasis. The (1→3)-β-D-glucan (BG) assay, a panfungal antigen test, is recommended as a complementary tool for the diagnosis of invasive mycoses in high-risk hemato-oncological patients. Its role in the more heterogeneous ICU population remains to be defined. More efficient clinical selection strategies combined with performant laboratory tools are needed in order to treat the right patients at the right time by keeping costs of screening and therapy as low as possible. The new approach proposed by Posteraro and colleagues in the previous issue of Critical Care meets these requirements. A single positive BG value in medical patients admitted to the ICU with sepsis and expected to stay for more than 5 days preceded the documentation of candidemia by 1 to 3 days with an unprecedented diagnostic accuracy. Applying this one-point fungal screening on a selected subset of ICU patients with an estimated 15 to 20% risk of developing candidemia is an appealing and potentially cost-effective approach. If confirmed by multicenter investigations, and extended to surgical patients at high risk of invasive candidiasis after abdominal surgery, this bayesian-based risk stratification approach aimed at maximizing clinical efficiency by minimizing health care resource utilization may substantially simplify the management of critically ill patients at risk of invasive candidiasis.

Topics: beta-Glucans; Candida; Candidemia; Female; Humans; Male; Sepsis