epiglucan and Candidiasis--Invasive

Neonatal invasive candidiasis (NIC) is a leading cause of infection-related morbidity and mortality in preterm neonates. Several studies have shown that (1,3)-Beta-d-glucan (BDG) was accurate in detecting invasive fungal infection in adults, but studies in neonates are scarce. The aim was to obtain summary estimates of the accuracy of BDG detection in serum for the diagnosis of NIC.. We searched Medline, Embase, Clinicaltrials.gov, and Google Scholar (inception to July 2019). We checked the reference lists of included studies, clinical guidelines, and review articles. We included studies that assessed the accuracy of BDG against a reference standard that defined groups of patients with ordinal levels of NIC probability (e.g. proven, probable, possible) and included fungal blood culture. Participants were neonates suspected of having NIC. The intervention was BDG measurement in serum (Fungitell® assay). We assessed risk of bias and applicability using QUADAS-2. We used bivariate meta-analysis to produce summary estimates of diagnostic accuracy at prespecified positivity thresholds of 80 and 120 pg/mL. This study was registered with PROSPERO (CRD42018089545).. We included eight studies (465 participants). Of these, two were judged at low overall risk of bias. There was substantial variability across studies in the reference standards used. At a positivity threshold of 80 pg/mL, summary estimates of sensitivity and specificity of BDG were 89% (95% CI: 80-94%) and 60% (53-66%), respectively; summary sensitivity for detecting proven cases of NIC was 99% (93-100%). At a positivity threshold of 120 pg/mL, summary estimates of sensitivity and specificity were 81% (71-88%) and 80% (67-88%), respectively.. Because of high sensitivity, BDG seems promising to rule-out NIC. It might be too early to recommend its use because of the scarcity of reliable clinical data, heterogeneity in case definitions, and unstable accuracy estimates.

Topics: Age Factors; beta-Glucans; Biomarkers; Candidiasis, Invasive; Humans; Infant, Newborn; Proteoglycans; Reproducibility of Results; ROC Curve; Sensitivity and Specificity

Invasive fungal infections (IFIs) are life-threatening opportunistic infections that occur in immunocompromised or critically ill people. Early detection and treatment of IFIs is essential to reduce morbidity and mortality in these populations. (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in the serum of infected individuals. The serum BDG test is a way to quickly detect these infections and initiate treatment before they become life-threatening. Five different versions of the BDG test are commercially available: Fungitell, Glucatell, Wako, Fungitec-G, and Dynamiker Fungus.. To compare the diagnostic accuracy of commercially available tests for serum BDG to detect selected invasive fungal infections (IFIs) among immunocompromised or critically ill people.. We searched MEDLINE (via Ovid) and Embase (via Ovid) up to 26 June 2019. We used SCOPUS to perform a forward and backward citation search of relevant articles. We placed no restriction on language or study design.. We included all references published on or after 1995, which is when the first commercial BDG assays became available. We considered published, peer-reviewed studies on the diagnostic test accuracy of BDG for diagnosis of fungal infections in immunocompromised people or people in intensive care that used the European Organization for Research and Treatment of Cancer (EORTC) criteria or equivalent as a reference standard. We considered all study designs (case-control, prospective consecutive cohort, and retrospective cohort studies). We excluded case studies and studies with fewer than ten participants. We also excluded animal and laboratory studies. We excluded meeting abstracts because they provided insufficient information.. We followed the standard procedures outlined in the Cochrane Handbook for Diagnostic Test Accuracy Reviews. Two review authors independently screened studies, extracted data, and performed a quality assessment for each study. For each study, we created a 2 × 2 matrix and calculated sensitivity and specificity, as well as a 95% confidence interval (CI). We evaluated the quality of included studies using the Quality Assessment of Studies of Diagnostic Accuracy-Revised (QUADAS-2). We were unable to perform a meta-analysis due to considerable variation between studies, with the exception of Candida, so we have provided descriptive statistics such as receiver operating characteristics (ROCs) and forest plots by test brand to show variation in study results.. We included in the review 49 studies with a total of 6244 participants. About half of these studies (24/49; 49%) were conducted with people who had cancer or hematologic malignancies. Most studies (36/49; 73%) focused on the Fungitell BDG test. This was followed by Glucatell (5 studies; 10%), Wako (3 studies; 6%), Fungitec-G (3 studies; 6%), and Dynamiker (2 studies; 4%). About three-quarters of studies (79%) utilized either a prospective or a retrospective consecutive study design; the remainder used a case-control design. Based on the manufacturer's recommended cut-off levels for the Fungitell test, sensitivity ranged from 27% to 100%, and specificity from 0% to 100%. For the Glucatell assay, sensitivity ranged from 50% to 92%, and specificity ranged from 41% to 94%. Limited studies have used the Dynamiker, Wako, and Fungitec-G assays, but individual sensitivities and specificities ranged from 50% to 88%, and from 60% to 100%, respectively. Results show considerable differences between studies, even by manufacturer, which prevented a formal meta-analysis. Most studies (32/49; 65%) had no reported high risk of bias in any of the QUADAS-2 domains. The QUADAS-2 domains that had higher risk of bias included participant selection and flow and timing.. We noted considerable heterogeneity between studies, and these differences precluded a formal meta-analysis. Because of wide variation in the results, it is not possible to estimate the diagnostic accuracy of the BDG test in specific settings. Future studies estimating the accuracy of BDG tests should be linked to the way the test is used in clinical practice and should clearly describe the sampling protocol and the relationship of time of testing to time of diagnosis.

Topics: Aspergillosis; beta-Glucans; Biomarkers; Candidiasis, Invasive; Case-Control Studies; Critical Illness; Humans; Immunocompromised Host; Invasive Fungal Infections; Pneumocystis carinii; Pneumocystis Infections; Prospective Studies; Retrospective Studies; ROC Curve; Sensitivity and Specificity

A high prevalence of invasive candidiasis has been reported in recent years. Patients admitted to an intensive care unit are at the highest risk for invasive candidiasis, mostly due to the severity of their disease, immune-suppressive states, prolonged length of stay, broad-spectrum antibiotics, septic shock, and Candida colonization. Intraabdominal candidiasis comprises a range of clinical manifestations, from just the suspicion based on clinical scenario to fever, leukocytosis, increase in biomarkers to the isolation of the responsible microorganism. In critically ill patients with IAC prompt treatment and adequate source control remains the ultimate goal.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Invasive; Critical Illness; Humans; Intensive Care Units; Intraabdominal Infections; Mannans; Procalcitonin; Risk Factors; Severity of Illness Index

Invasive fungal diseases carry a high mortality risk which can be reduced by early treatment. Diagnosing invasive fungal diseases is challenging, because invasive methods for obtaining histological samples are frequently not feasible in thrombocytopenic immunocompromised patients, while fungal cultures have low sensitivity and a long turn-around time. Non-cultural methods are fundamental for a rapid diagnosis of invasive fungal diseases and they include assays based on the detection of fungal antigens (galactomannan, Aspergillus-lateral flow device, [1,3]-β-D-glucan, mannan), antibodies, such as anti-mannan, and molecular tests. With the exception of some molecular methods for rare fungi, the non-cultural assays are usually applied to the diagnosis of invasive aspergillosis, invasive candidiasis and pneumocystosis. The performance of a single test or a combination of tests will be discussed, with particular focus on choosing the most appropriate marker(s) for every specific patient population. Reasons for potential false-positive or false-negative results will be discussed.

Topics: Antigens, Fungal; beta-Glucans; Candidiasis, Invasive; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Microbiological Techniques; Polymerase Chain Reaction

Topics: Antigens, Fungal; beta-Glucans; Candidiasis, Invasive; Galactose; Humans; Mannans; Mycoses; Proteoglycans; Pulmonary Aspergillosis; Serologic Tests

Blood cultures are limited for diagnosing invasive candidiasis by poor sensitivity and slow turn-around time. New diagnostics are needed to complement cultures, in particular to identify the "missing 50%" of patients who are blood culture-negative. Mannan/anti-mannan immunoglobulin G, β-D-glucan (BDG) and polymerase chain reaction (PCR) assays can diagnose candidemia before blood cultures and show promising sensitivity/specificity, but they are not widely investigated in blood culture-negative, deep-seated candidiasis. In a recent study, BDG and PCR were superior to blood cultures in deep-seated candidiasis, suggesting they may identify currently undiagnosed patients and expand our understanding of disease spectrum. Positive predictive values of nonculture tests are limited by the low prevalence of invasive candidiasis, which mandates that results be interpreted judiciously. When used as biomarkers that assess a patient's risk of having invasive candidiasis, tests will facilitate preemptive antifungal strategies. Because negative predictive values are excellent, tests will also be useful for ruling out invasive candidiasis and discontinuing unnecessary antifungal therapy.

Topics: beta-Glucans; Biomarkers; Candidiasis, Invasive; Clinical Laboratory Techniques; DNA, Fungal; Humans; Patient Care; Predictive Value of Tests; Sensitivity and Specificity

Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.

Topics: Aspergillosis; beta-Glucans; Candidiasis, Invasive; Female; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Proteoglycans; ROC Curve; Sensitivity and Specificity; Serum

Although invasive fungal infections (IFIs) are relatively rare, they are important causes of morbidity and mortality in immunocompromised pediatric patients. Early and precise diagnosis of IFI is important to allow antifungal treatment to be started in time and to reduce the unnecessary use of toxic antifungal agents. Although traditional approaches such as direct microscopic examination, histopathological evaluation and cultivation are still gold standard, the diagnosis of IFI is generally difficult because of inadequate sensitivity and specificity with these tests. Commercial systems detecting the Aspergillus cell wall antigen galactomannan and 1,3-β-D-glucan are seen as the most convenient nonculture methods for the diagnosis of the IFI and monitoring of antifungal treatment. Several molecular methods have been described for the diagnosis of opportunistic mycoses. However, they have not been standardized and have only been used in experimental studies.

Topics: Aspergillosis; Aspergillus; beta-Glucans; Candida; Candidiasis, Invasive; Child; Culture Techniques; Diagnostic Techniques and Procedures; Early Diagnosis; Galactose; Humans; Mannans; Sensitivity and Specificity

The (1→3)-β-D-Glucan (BG) assay has been approved for diagnosing invasive fungal disease (IFD). However, the test performance has been variable. We conducted a meta-analysis to determine the overall accuracy of BG assay for diagnosing IFD.. The sensitivity, specificity, and positive and negative likelihood ratios (PLR and NLR, respectively) of BG for diagnosing IFD were pooled using a bivariate meta-analysis. We also performed subgroup analyses.. Twelve reports, including 15 studies, were included for the analysis (proven and probable IFD vs possible or no IFD). The sensitivity, specificity, PLR and NLR were 0.76 (95% CI, 0.67-0.83), 0.85 (95% CI, 0.73-0.92), 5.05 (95% CI, 2.71-9.43), and 0.28 (95% CI, 0.20-0.39), respectively. Subgroup analyses showed that the BG assay had higher specificities for patients with hematological disorders and a positive BG result with two consecutive samples. The combination of galactomannan and BG increased the specificity value to 0.98 (95% CI, 0.95-0.99) for diagnosing invasive aspergillosis.. Serum BG determination is clinically useful for diagnosing IFD in at-risk patients, especially for hematology patients. The combination of galactomannan and BG was sufficient for diagnosing invasive aspergillosis. Since the BG assay is not absolutely sensitive and specific for IFD, the BG results should be interpreted in parallel with clinical findings.

Topics: Aspergillosis; beta-Glucans; Biomarkers; Candidiasis, Invasive; Galactose; Humans; Likelihood Functions; Linear Models; Mannans; Mycoses; Proteoglycans; ROC Curve; Sensitivity and Specificity

To investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI).. Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality.. 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80-1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0-2.2] days in the BDG group and 4.4 (IQR 2.0-9.1, p < 0.01) days in the control group.. Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

Topics: Adult; Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Glucans; Humans; Sensitivity and Specificity; Sepsis

The time to diagnosis of invasive Candida infection (ICI) is often too long to initiate timely antifungal therapy in patients with sepsis. Elevated serum (1,3)-β-D-glucan (BDG) concentrations have a high diagnostic sensitivity for detecting ICI. However, the clinical significance of elevated BDG concentrations is unclear in critically ill patients. The goal of this study is to investigate whether measurement of BDG in patients with sepsis and a high risk for ICI can be used to decrease the time to empiric antifungal therapy and thus, increase survival.. This prospective multicenter open randomized controlled trial is being conducted in 19 German intensive care units. All adult patients with severe sepsis or septic shock and an increased risk for ICI are eligible for enrolment. Risk factors are total parenteral nutrition, previous abdominal surgery, previous antimicrobial therapy, and renal replacement therapy. Patients with proven ICI or those already treated with systemic antifungal substances are excluded. Patients are allocated to a BDG or standard care group. The standard care group receives targeted antifungal therapy as necessary. In the BDG group, BDG serum samples are taken after randomization and 24 h later. Antifungal therapy is initiated if BDG is ≥80 pg/ml in at least one sample. We plan to enroll 312 patients. The primary outcome is 28-day mortality. Other outcomes include antifungal-free survival within 28 days after enrolment, time to antifungal therapy, and the diagnostic performance of BDG compared to other laboratory tests for early ICI diagnosis. The statistical analysis will be performed according to the intent-to-treat principle.. Because of the high risk of death, American guidelines recommend empiric antifungal therapy in sepsis patients with a high risk of ICI despite the limited evidence for such a recommendation. In contrast, empiric antifungal therapy is not recommended by European guidelines. BDG may offer a way out of this dilemma since BDG potentially identifies patients in need of early antifungals. However, the evidence for such an approach is inconclusive. This clinical study will generate solid evidence for health-care providers and authors of guidelines for the use of BDG in critically ill patients.. Clinicaltrials.gov, NCT02734550 . Registered 12 April 2016.

Topics: Antifungal Agents; Bacteriological Techniques; beta-Glucans; Biomarkers; Candida; Candidiasis, Invasive; Early Diagnosis; Female; Germany; Humans; Male; Multicenter Studies as Topic; Predictive Value of Tests; Prospective Studies; Proteoglycans; Randomized Controlled Trials as Topic; Reproducibility of Results; Sepsis; Severity of Illness Index; Time Factors; Time-to-Treatment; Up-Regulation

The aim of this study was to determine the impact of a biomarker-based strategy on early discontinuation of empirical antifungal treatment.. Prospective randomized controlled single-center unblinded study, performed in a mixed ICU. A total of 110 patients were randomly assigned to a strategy in which empirical antifungal treatment duration was determined by (1,3)-β-D-glucan, mannan, and anti-mannan serum assays, performed on day 0 and day 4; or to a routine care strategy, based on international guidelines, which recommend 14 days of treatment. In the biomarker group, early stop recommendation was determined using an algorithm based on the results of biomarkers. The primary outcome was the percentage of survivors discontinuing empirical antifungal treatment early, defined as a discontinuation strictly before day 7.. A total of 109 patients were analyzed (one patient withdraw consent). Empirical antifungal treatment was discontinued early in 29 out of 54 patients in the biomarker strategy group, compared with one patient out of 55 in the routine strategy group [54% vs 2%, p < 0.001, OR (95% CI) 62.6 (8.1-486)]. Total duration of antifungal treatment was significantly shorter in the biomarker strategy compared with routine strategy [median (IQR) 6 (4-13) vs 13 (12-14) days, p < 0.0001). No significant difference was found in the percentage of patients with subsequent proven invasive Candida infection, mechanical ventilation-free days, length of ICU stay, cost, and ICU mortality between the two study groups.. The use of a biomarker-based strategy increased the percentage of early discontinuation of empirical antifungal treatment among critically ill patients with suspected invasive Candida infection. These results confirm previous findings suggesting that early discontinuation of empirical antifungal treatment had no negative impact on outcome. However, further studies are needed to confirm the safety of this strategy. This trial was registered at ClinicalTrials.gov, NCT02154178.

Topics: Aged; Algorithms; Antibodies, Fungal; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Invasive; Critical Illness; Drug Administration Schedule; Female; Humans; Intensive Care Units; Male; Mannans; Middle Aged; Predictive Value of Tests; Prospective Studies; Proteoglycans

Patients undergoing emergency gastrointestinal surgery for intra-abdominal infection are at risk of invasive candidiasis (IC) and candidates for preemptive antifungal therapy.. This exploratory, randomized, double-blind, placebo-controlled trial assessed a preemptive antifungal approach with micafungin (100 mg/d) in intensive care unit patients requiring surgery for intra-abdominal infection. Coprimary efficacy variables were the incidence of IC and the time from baseline to first IC in the full analysis set; an independent data review board confirmed IC. An exploratory biomarker analysis was performed using logistic regression.. The full analysis set comprised 124 placebo- and 117 micafungin-treated patients. The incidence of IC was 8.9% for placebo and 11.1% for micafungin (difference, 2.24%; [95% confidence interval, -5.52 to 10.20]). There was no difference between the arms in median time to IC. The estimated odds ratio showed that patients with a positive (1,3)-β-d-glucan (ßDG) result were 3.66 (95% confidence interval, 1.01-13.29) times more likely to have confirmed IC than those with a negative result.. This study was unable to provide evidence that preemptive administration of an echinocandin was effective in preventing IC in high-risk surgical intensive care unit patients with intra-abdominal infections. This may have been because the drug was administered too late to prevent IC coupled with an overall low number of IC events. It does provide some support for using ßDG to identify patients at high risk of IC.. NCT01122368.

Topics: Adolescent; Adult; Aged; Antifungal Agents; beta-Glucans; Biomarkers; Candidiasis, Invasive; Double-Blind Method; Echinocandins; Female; Humans; Intensive Care Units; Intraabdominal Infections; Lipopeptides; Male; Micafungin; Middle Aged; Postoperative Complications; Pre-Exposure Prophylaxis; Proteoglycans; Young Adult

(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

Invasive candidiasis (IC) is a devastating disease. While prompt antifungal therapy improves outcomes, empiric treatment based on the presence of fever has little clinical impact. Β-D-Glucan (BDG) is a fungal cell wall component detectable in the serum of patients with early invasive fungal infection (IFI). We evaluated the utility of BDG surveillance as a guide for preemptive antifungal therapy in at-risk intensive care unit (ICU) patients.. Patients admitted to the ICU for ≥ 3 days and expected to require at least 2 additional days of intensive care were enrolled. Subjects were randomized in 3:1 fashion to receive twice weekly BDG surveillance with preemptive anidulafungin in response to a positive test or empiric antifungal treatment based on physician preference.. Sixty-four subjects were enrolled, with 1 proven and 5 probable cases of IC identified over a 2.5 year period. BDG levels were higher in subjects with proven/probable IC as compared to those without an IFI (117 pg/ml vs. 28 pg/ml; p<0.001). Optimal assay performance required 2 sequential BDG determinations of ≥ 80 pg/ml to define a positive test (sensitivity 100%, specificity 75%, positive predictive value 30%, negative predictive value 100%). In all, 21 preemptive and 5 empiric subjects received systemic antifungal therapy. Receipt of preemptive antifungal treatment had a significant effect on BDG concentrations (p< 0.001). Preemptive anidulafungin was safe and generally well tolerated with excellent outcome.. BDG monitoring may be useful for identifying ICU patients at highest risk to develop an IFI as well as for monitoring treatment response. Preemptive strategies based on fungal biomarkers warrant further study.. Clinical Trials.gov NCT00672841.

Topics: Adult; Aged; Aged, 80 and over; Anidulafungin; Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Demography; Echinocandins; False Positive Reactions; Feasibility Studies; Female; Humans; Intensive Care Units; Kinetics; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Time Factors; Young Adult

This study was conducted as a prospective, multicenter trial to evaluate the efficacy and safety of micafungin as an empirical therapy for suspected invasive fungal infections (IFIs), including febrile neutropenia (FN), and to evaluate the usefulness of β-D: -glucan (BG) and Aspergillus galactomannan (GM) antigen in patients with hematologic diseases. A total of 121 patients were enrolled and assessed for safety, and 119 were examined for clinical efficacy. The main underlying diseases were acute myeloid leukemia (38.0%), acute lymphoblastic leukemia (18.2%), and malignant lymphoma (18.2%). The median initial daily dose and duration of micafungin treatment were 150 mg/day and 13 days, respectively. The overall response rate for suspected IFIs (n = 119), based on four composite endpoints, including baseline IFI, breakthrough IFIs (proven and probable), survival, and premature discontinuation, was 79.0%. In addition, the response rate for FN (n = 81), based on these four endpoints as well as defervescence during neutropenia, was 39.5%. Breakthrough IFIs (proven, probable, and possible) occurred in five patients during micafungin treatment. All of these patients were positive for either BG or GM before the breakthrough IFIs. The incidence of adverse events (AEs) associated with micafungin was 10.7% and most were mild. The majority of AEs were liver dysfunction. These results indicate the effectiveness and safety of micafungin as an empirical therapy for suspected IFIs, including FN, and the usefulness of monitoring both BG and GM to detect breakthrough IFIs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Bacterial; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Chemical and Drug Induced Liver Injury; Early Diagnosis; Echinocandins; Female; Galactose; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; Lipopeptides; Lymphoma; Male; Mannans; Micafungin; Middle Aged; Mycoses; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Young Adult

Topics: beta-Glucans; Candidiasis, Invasive; Humans; Intensive Care Units; 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

This study aimed to characterize the baseline values and dynamics of serum (1,3)-Beta-D-Glucan (BDG) in neonates at high risk of neonatal invasive candidiasis (NIC); as well as to determine the effect of various clinical variables on these levels. Single center prospective cohort study was performed including 20 high-risk neonates (gestational age < 29 weeks and/or birth weight ≤ 1000 gr). Samples for BDG (Fungitell® assay) were obtained twice weekly during 6 weeks. Nineteen neonates were enrolled with a median gestational age of 25 weeks (IQR 24-27), median birth weight of 730 gr (IQR 650-810). None of the neonates was diagnosed with NIC. 190 serum samples were included. The median BDG value was 59 pg/ml (IQR 30-148), mean was 119 pg/ml (SD ± 154). A total of 42.1% (80/190) samples showed values ≥80 pg/ml, with all the neonates presenting at least one test above this cut-off. Neonatal age did not show an association with BDG levels. Exposure to steroids and the use of a heel prick as sampling method were associated with statistically significant higher BDG levels. The BDG levels showed high variability and in a significant proportion of samples values were above the threshold for positivity (e.g., ≥80 pg/ml) in the absence of NIC. The exposure to postnatal steroids and the heel prick as the method of blood sampling were associated with higher BDG levels.. Neonatal invasive candidiasis (NIC) presents high morbi-mortality. The diagnosis of NIC is often challenging. Blood cultures have limitations and better diagnostic tools are needed. Beta-D-glucan is a diagnostic marker which could be potentially used, although still more clinical data are required.

Topics: Animals; beta-Glucans; Birth Weight; Candidiasis; Candidiasis, Invasive; Humans; Prospective Studies; Sensitivity and Specificity

(1,3)-β-D-glucan (BD) assays were developed as a method to rapidly diagnose invasive candidiasis (IC). The incidence of fungal infections and the demands for BD assay are gradually increasing in patients with severe trauma and under intensive care. However, the ideal BD cut-off value to predict IC has not been clarified. In this study, we evaluate the predictability of the BD assay and investigate the optimal cut-off value in patients with severe burn injuries.. From July to December 2018, 134 samples from 86 patients with severe burns were analyzed. Serum BD levels were measured utilizing a Fungitell (Cape Cod Inc.) assay. A receiver operator characteristic (ROC) curve was generated, and the cumulative progression of IC was studied using a Cox proportional hazards model. Partial dependence plots (PDP) was applied to predict the risk of IC.. Eleven patients were diagnosed with IC. BD over 120 pg/mL (HR = 8.68; P = 0.001) was found to be independent predictor of the occurrence of IC, when the multivariable Cox model was adjusted for age, total body surface area, inhalation injury, and antifungal agents. The area under the ROC curve was 0.658 (95% CI, 0.513-0.803), at an optimal cut-off value of 124.7 pg/mL. PDP analysis showed the higher predicted IC occurrence at a BD level of 120-150 pg/mL and TBSA over 60%.. Our findings suggest that BD is an independent predictor for IC, and that a BD level between 120 and 150 pg/mL could be utilized for IC prediction.

Topics: beta-Glucans; Burns; Candidiasis, Invasive; Glucans; Humans; Proteoglycans; ROC Curve

Topics: beta-Glucans; Biomarkers; Candida; Candidiasis; Candidiasis, Invasive; Humans; Sensitivity and Specificity

We assessed the diagnostic accuracy of serum (1 → 3)-β-D-glucan (BDG) for neonatal invasive candidiasis (NIC) using the recommended cut-off usually used in adults for detecting invasive candidiasis and searched for an optimal cut-off for ruling out NIC.. We conducted a prospective cross-sectional study at Nantes University medical centre from January 2017 to July 2018. All consecutive newborn infants of less than 28 days of corrected age, with clinically suspected NIC, who underwent BDG assay, were included. Sensitivity and specificity were calculated by using the recommended cut-off of 80 pg/mL. Receiver operating characteristic curve analysis was used to identify an optimal cut-off value.. We included 55 newborn infants with 61 episodes of suspected NIC. Their median gestational and chronological ages were 28.0 weeks (interquartile range [IQR] 26.4-34.1) and 10.0 days (IQR 6.0-22.0), respectively. Of 61 episodes, seven revealed NIC. Sensitivity and specificity were 85.7% (95% confidence interval [CI] 42.1%-99.6%) and 51.9% (37.8%-65.7%) with the recommended cut-off, respectively. An optimal cut-off of 174 pg/mL offered the same sensitivity but higher specificity 77.8% (64.4%-88.0%).. The recommended cut-off of 80 pg/mL was probably too low for ruling out NIC. A higher cut-off might have been more appropriate.

Topics: Adult; beta-Glucans; Candidiasis, Invasive; Cross-Sectional Studies; Humans; Infant; Infant, Newborn; Prospective Studies; Sensitivity and Specificity

While the serological detection of (1→3)-β-D-glucan (BDG) can indicate invasive fungal disease (IFD), false positivity occurs. Nevertheless, the presence of BDG can still be recognized by the host's innate immune system and persistent BDG antigenemia, in the absence of IFD, can result in deleterious proinflammatory immune responses.. During the XXX (INTENSE) study into the preemptive use of micafungin to prevent invasive candidiasis (IC) after abdominal surgery, the serum burden of BDG was determined to aid diagnosis of IC. Data from the INTENSE study were analyzed to determine whether BDG was associated with organ failure and patient mortality, while accounting for the influences of IC and antifungal therapy.. A BDG concentration >100 pg/mL was associated with a significantly increased Sequential Organ Failure Assessment score (≤100 pg/mL: 2 vs >100 pg/mL: 5; P < .0001) and increased rates of mortality (≤100 pg/mL: 13.7% vs >100 pg/mL: 39.0%; P = .0002). Multiple (≥2) positive results >100 pg/mL or a BDG concentration increasing >100 pg/mL increased mortality (48.1%). The mortality rate in patients with IC and a BDG concentration >100 pg/mL and ≤100 pg/mL was 42.3% and 25.0%, respectively. The mortality rate in patients without IC but a BDG concentration >100 pg/mL was 37.3%. The use of micafungin did not affect the findings.. The presence of persistent or increasing BDG in the patient's circulation is associated with significant morbidity and mortality after abdominal surgery, irrespective of IC. The potential lack of a specific therapeutic focus has consequences when trying to manage these patients, and when designing clinical trials involving patients where host-associated BDG concentrations may be elevated.. NCT01122368.

Topics: beta-Glucans; Candidiasis, Invasive; Glucans; Humans; Micafungin; Prognosis; Sensitivity and Specificity

Topics: Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Glucans; Humans; Proteoglycans

Detection of 1,3-β-d-glucan (BDG) in serum has been evaluated for its inclusion as a mycological criterion of invasive fungal infections (IFI) according to EORTC and Mycoses Study Group (MSG) definitions. BDG testing may be useful for the diagnosis of both invasive aspergillosis and invasive candidiasis, when interpreted in conjunction with other clinical/radiological signs and microbiological markers of IFI. However, its performance and utility vary according to patient population (hematologic cancer patients, solid-organ transplant recipients, intensive care unit patients) and pretest likelihood of IFI. The objectives of this article are to provide a systematic review of the performance of BDG testing and to assess recommendations for its use and interpretation in different clinical settings.

Topics: Adult; beta-Glucans; Candidiasis, Invasive; Glucans; Humans; Invasive Fungal Infections; Sensitivity and Specificity

Chronic disseminated candidiasis (CDC) is a type of invasive candidiasis. CDC commonly appears in the neutrophil recovery phase after chemotherapy in patients with hematologic malignancies, and immune reconstitution inflammatory syndrome (IRIS) is thought to play a major role in CDC development. This report describes the case of a 33-year-old man with CDC as a complication of acute myeloid leukemia. We describe the clinical course, body temperature, therapy, and (1,3)-β-D-glucan (BDG) levels over the course of 22 months. He was initially treated with antifungals, but corticosteroids were added because of a persistently elevated body temperature, which we attributed to IRIS. After starting corticosteroids, his clinical condition improved, but his BDG levels became markedly elevated. We hypothesize that the suppression of the excessive immune response by corticosteroids lead to granuloma collapse, fungal release, and hematogenous dissemination, resulting in elevated BDG levels. The patient's condition gradually improved over the course of follow-up.

Topics: Adrenal Cortex Hormones; Adult; Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Humans; Male; Proteoglycans

Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and β-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.

Topics: Antifungal Agents; beta-Glucans; Candidiasis, Invasive; DNA Probes; Female; Humans; Intraabdominal Infections; Male; Middle Aged; Multiplex Polymerase Chain Reaction; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity

The Fungitell assay (FA) and the Wako β-glucan test (GT) are employed to measure the serum/plasma 1,3-β-D-glucan (BDG), a well-known invasive fungal disease biomarker. Data to convincingly and/or sufficiently support the GT as a valuable alternative to the FA are yet limited. In this study, we evaluated the FA and the GT to diagnose invasive aspergillosis (IA), invasive candidiasis (IC), and Pneumocystis jirovecii pneumonia (PJP). The FA and GT performances were compared in sera of patients with IA (n = 40), IC (n = 78), and PJP (n = 17) with respect to sera of control patients (n = 187). Using the manufacturer's cutoff values of 80 pg/mL and 11 pg/mL, the sensitivity and specificity for IA diagnosis were 92.5% and 99.5% for the FA and 60.0% and 99.5% for the GT, respectively; for IC diagnosis were 100.0% and 97.3% for the FA and 91.0% and 99.5% for the GT, respectively; for PJP diagnosis were 100.0% and 97.3% for the FA and 88.2% and 99.5% for the GT, respectively. When an optimized cutoff value of 7.0 pg/mL for the GT was used, the sensitivity and specificity were 80.0% and 97.3% for IA diagnosis, 98.7% and 97.3% for IC diagnosis, and 94.1% and 97.3% for PJP diagnosis, respectively. At the 7.0-pg/mL GT cutoff, the agreement between the assays remained and/or became excellent for IA (95.1%), IC (97.3%), and PJP (96.5%), respectively. In conclusion, we show that the GT performed as well as the FA only with a lowered cutoff value for positivity. Further studies are expected to establish the equivalence of the two BDG assays.

Topics: Adult; Aged; Aspergillosis; Aspergillus; beta-Glucans; Candida albicans; Candidiasis, Invasive; Diagnostic Tests, Routine; Female; Humans; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; ROC Curve

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

Topics: Antibodies, Fungal; beta-Glucans; Biomarkers; Candida; Candida albicans; Candidiasis, Invasive; Early Diagnosis; Fluoroimmunoassay; Humans; Proteoglycans; Reagent Kits, Diagnostic; Retrospective Studies; Sensitivity and Specificity

In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis.. The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis. Over 5 days, we determined white blood cell count, 1,3-β-D-glucan, and HLA-DR expression; the amount of Th1, Th17, regulatory T, T helper, and cytotoxic T cells; Dectin-1 and TLR2-expression; the amount of T, B, and NK cells; the ex vivo secretion of IL-8 upon stimulation with LPS, flagellin, and zymosan; and the distribution of distinct T-cell cytokines in a daily manner. On day 21, patients' Candida infection status was stratified in no colonization or IC, colonization or IC.. A total of 26 patients were included. On day 21, five patients showed no colonization or IC, in 13 patients a colonization was detected, and eight patients were diagnosed with IC. On study inclusion, the stratification groups showed comparable values in standard laboratory parameters and morbidity scores. Decreased B and NK cell counts, as well as reduced IL-8 secretion after ex vivo stimulation with LPS or flagellin seemed to be associated with a higher risk of subsequent Candida colonization. Even lower values could distinguish the therapy-relevant difference between prospective IC from colonization alone.. We were able to show distinct immune system impairments in early abdominal sepsis by specific immune-based measurements. A possible association of these impairments with a subsequent Candida affection is shown.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Candidiasis, Invasive; Female; Flow Cytometry; Humans; Intensive Care Units; Interleukin-2 Receptor alpha Subunit; Interleukin-7 Receptor alpha Subunit; Lectins, C-Type; Male; Middle Aged; Monocytes; Neutrophils; Sepsis; T-Lymphocytes, Cytotoxic; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Toll-Like Receptor 2; Toll-Like Receptor 9

Diagnosis of invasive candidiasis (IC) is still challenging due to absence of specific clinical signs and symptoms. In this study we investigate the clinical value of (1,3)-β-D-glucan (BDG), mannan (MN), antimannan immunoglobulin G (AM-IgG), and antimannan immunoglobulin M (AM-IgM) assay in diagnosis of IC. During 2016 to 2018 serum samples from 71 patients with IC and 185 patients without IC were collected. Serum samples from 41 patients with bacteremia were also enrolled as additional control. Significant differences in mean serum biomarkers levels between IC and control group were observed. At low cutoff threshold the sensitivity and specificity of BDG (70 pg/ml), MN (50 pg/ml), AM-IgG (80 AU/ml), and AM-IgM (80 AU/ml) assay were 64.8% and 90.8%, 64.8 and 89.2%,74.6% and 87.0%, 57.7% and 60.0%, respectively. Combined use of BDG/MN, BDG/AM-IgG and MN/AM-IgG improved the sensitivity and specificity to 85.9% and 81.1%, 85.9% and 80.0%, 81.7% and 81.6%, respectively. The combination of BDG/MN, BDG/AM-IgG, or MN/AM-IgG may provide an encouraging approach for diagnosis of IC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Fungal; beta-Glucans; Biomarkers; Candidiasis, Invasive; Case-Control Studies; Diagnostic Tests, Routine; Female; Humans; Immunoglobulin G; Immunoglobulin M; Male; Mannans; Middle Aged; Proteoglycans; Retrospective Studies; Sensitivity and Specificity; Young Adult

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

We assessed the potential role of T2Candida MR (T2MR) and serological biomarkers [β-d-glucan (BDG) or Candida albicans germ tube antibodies (CAGTA)], alone or in combination with standard cultures, for identifying patients with suspected invasive candidiasis (IC), who may benefit from maintaining antifungal therapy.. Prospective observational multicentre study including all adult patients receiving empirical antifungal therapy for suspected IC, from January to June 2017. CAGTA, BDG and T2MR were determined at baseline and at +2 and +4 days after enrolment. Primary endpoint was the diagnostic value of CAGTA, BDG and T2MR, alone or in combination with standard culture, to predict diagnosis of IC and/or mortality in the first 7 days after starting antifungal therapy (poor outcome).. Overall, 14/49 patients (28.6%) had a poor outcome (7 died within the first 7 days of antifungal therapy, whereas 7 ended with a diagnosis of IC). CAGTA [3/14 (21.4%) versus 8/35 (22.9%), P = 1] and BDG [8/14 (57.1%) versus 17/35 (48.6%), P = 0.75] results were similar in poor- and good-outcome patients. Conversely, a positive T2MR was associated with a higher risk of poor outcome [5/14 (35.7%) versus 0/35 (0.0%) P = 0.0001]. Specificity and positive predictive value of a positive T2MR for predicting poor outcome were both 100%, with a negative predictive value of 79.6%. After testing the combinations of biomarkers/standard cultures and T2MR/standard cultures, the combination of T2MR/standard cultures showed a high capacity to discriminate patients with poor outcome from those with good clinical evolution.. T2MR may be of significant utility to identify patients who may benefit from maintaining antifungal therapy.

Topics: Adult; Aged; Antibodies, Fungal; Antifungal Agents; beta-Glucans; Blood Culture; Candidiasis; Candidiasis, Invasive; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pilot Projects; Prospective Studies

Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-β-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-β-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P: <.0001). The sensitivity, specificity, and diagnostic odds ratio for proven/probable IFD was 81.4%, 78.1%, and 15.5, respectively. Significant BDG false positivity (9/13) was associated post abdominal surgery. D-BDG showed fair and good agreement with the Fungitell®, and GM assays, respectively. In conclusion, the D-BDG provides a useful adjunct test to aid the diagnosis of IFD, with technical flexibility that will assist laboratories processing low sample numbers. Further, large scale, prospective evaluation is required to confirm the clinical validity and determine clinical utility.

Topics: Aspergillosis; beta-Glucans; Candidiasis, Invasive; Diagnostic Tests, Routine; Female; Fungal Polysaccharides; Humans; Male; Middle Aged; Pneumonia, Pneumocystis; Sensitivity and Specificity

Invasive fungal infections are important causes of morbimortality in critical patients. Most of these infections are caused by Candida spp. which diagnosis has important limitations.. Initial evaluation of the utility of 1,3-β-D-glucan (BDG) as a diagnostic tool for invasive candida infections in critical patients.. Adult patients over 18 years old, hospitalized in intensive care units for more than five days, with fever > 38 °C of unclear origin and two or more risk factors for invasive Candida spp. infection were included. Samples for BDG were obtained on two consecutive days. The results were compared with definitive diagnosis of candidemia/invasive candidiasis (C/IC) confirmed by cultures.. Median value of BDG in patients with C/IC was 224.3 ± 213.7 pg/ml and in patients without C/IC was 63.8 ± 76.7 pg/ml (p: 0.02). Sensitivity and specificity for the diagnosis of C/IC were 60 and 92%, respectively. Positive predictive value was 60% and negative predictive value was 92%.. BDG could be considered as a complementary diagnostic tool for the diagnosis of C/IC in critical patients with risk factors.

Topics: Adult; Aged; Aged, 80 and over; beta-Glucans; Biomarkers; Candidiasis, Invasive; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Proteoglycans; Risk Factors; Sensitivity and Specificity; Young Adult

Early initiation of antifungal treatment for invasive candidiasis is associated with change in mortality. Beta-D-glucan (BDG) is a fungal cell wall component and a serum diagnostic biomarker of fungal infection. Clinical findings suggested an association between reduced invasive candidiasis incidence in intensive care units (ICUs) and BDG-guided preemptive antifungal therapy. We evaluated the potential cost-effectiveness of active BDG surveillance with preemptive antifungal therapy in patients admitted to adult ICUs from the perspective of Hong Kong healthcare providers. A Markov model was designed to simulate the outcomes of active BDG surveillance with preemptive therapy (surveillance group) and no surveillance (standard care group). Candidiasis-associated outcome measures included mortality rate, quality-adjusted life year (QALY) loss, and direct medical cost. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of model results. In base-case analysis, the surveillance group was more costly (1387 USD versus 664 USD) (1 USD = 7.8 HKD), with lower candidiasis-associated mortality rate (0.653 versus 1.426 per 100 ICU admissions) and QALY loss (0.116 versus 0.254) than the standard care group. The incremental cost per QALY saved by the surveillance group was 5239 USD/QALY. One-way sensitivity analyses found base-case results to be robust to variations of all model inputs. In probabilistic sensitivity analysis, the surveillance group was cost-effective in 50 % and 100 % of 10,000 Monte Carlo simulations at willingness-to-pay (WTP) thresholds of 7200 USD/QALY and ≥27,800 USD/QALY, respectively. Active BDG surveillance with preemptive therapy appears to be highly cost-effective to reduce the candidiasis-associated mortality rate and save QALYs in the ICU setting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Chemoprevention; Cost-Benefit Analysis; Decision Support Techniques; Diagnostic Tests, Routine; Female; Health Care Costs; Hong Kong; Humans; Intensive Care Units; Male; Middle Aged; Outcome Assessment, Health Care; Treatment Outcome; Young Adult

The objective of this study was to investigate the prognostic potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid (BALF) samples.. A total of 300 BALF samples from 252 patients were investigated for BDG (Fungitell(®) assay). Prognostic potential of BALF BDG was evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard regression analyses.. BALF BDG levels were found to be significantly higher in samples with Candida spp. colonization (p < 0.001). A total of 61/252 patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with BALF BDG <200 pg/mL, 32.4% with BALF BDG ≥200 pg/mL). Kaplan-Meier analysis revealed that overall cumulative 90-day mortality was significantly higher in those with BALF BDG levels ≥200 pg/mL when compared to those with levels <200 pg/mL (log-rank p = 0.006, Breslow p = 0.005 and Tarone-Ware p = 0.005). The multivariable Cox regression analysis showed that BALF BDG levels were a strong predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100 pg/mL increase of BALF BDG).. False positive BALF BDG results in the presence of Candida spp. colonization of the lower respiratory tract may explain the limited diagnostic potential of BALF BDG testing. In contrast, prognostic potential of BALF BDG may be promising.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; beta-Glucans; Bronchoalveolar Lavage Fluid; Candidiasis, Invasive; Cohort Studies; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Pulmonary Aspergillosis; Risk Factors; Young Adult

Deeply invasive or disseminated candidiasis is a serious and often fatal complication that can occur frequently in immuno-compromised individuals. However, conventional diagnostic methods of Candida albicans display low sensitivity and lack of specificity; the development of rapid and accurate detection methods remains a high priority. Aptamers are single-strand DNA or RNA oligonucleotides that specifically bind to target molecules with high affinity. In this study, we sought to screen high-affinity DNA aptamers that specifically bound to (1→3)-β-D-glucans from cell wall of Candida albicans using a systematic evolution of ligands by exponential enrichment (SELEX) technique, and further evaluate the diagnostic potential for invasive or disseminated candidiasis with selected aptamers. (1→3)-β-D-glucans was purified from Candida albicans, and two single DNA aptamers (designated as AU1 and AD1) were selected. Analysis of dissociation constants and binding domains further revealed that these two selected single DNA aptamers (AU1 and AD1) showed high binding affinity (AD1: Kd = 79.76 nM, AD1: Kd = 103.7 nM) and did not bind to the same domain of (1→3)-β-D-glucans. Next, we further detected (1→3)-β-D-glucans in serum samples from different groups of patients with Candida albicans infection or simple bacterial infection by using a double-aptamer sandwich enzyme-linked oligonucleotide assay (ELONA). The results showed that the sensitivity and specificity of this aptamer-based sandwich ELONA were 92.31 % and 91.94 % respectively. Thus, our study suggests that AU1 and AD1 have potential application for the differentiate diagnosis of deeply invasive candidiasis and provide valuable clues for designing diagnostic agents for the identification of invasive fungal infection.

Topics: Antigens, Fungal; Aptamers, Nucleotide; beta-Glucans; Candida albicans; Candidiasis, Invasive; Clinical Laboratory Techniques; Diagnostic Tests, Routine; Humans; Proteoglycans; Sensitivity and Specificity

Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 μg ml

Topics: Amphotericin B; Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis, Invasive; Caspofungin; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Fluconazole; Kidney; Lipopeptides; Male; Mice; Microbial Sensitivity Tests; Microbial Viability; Proteoglycans; Survival Analysis; Treatment Outcome

There is a real medical need of new diagnostic tools for the early recognition of invasive Candida infections. We exploited a rather simple and rapid redox methodology to construct a bispecific monoclonal antibody (bsmAb) that combines a monoclonal antibody (mAb) directed against 1,3-β-D-glucan, a well-known, pan-fungal diagnostic biomarker, with a mAb recognizing MP65, a major immunogenic mannoprotein secreted by C.albicans and other Candida species. The bsmAb (MP65/bglu mAb) was successfully produced and purified at high yields and proved to bind and reveal simultaneously, with high sensitivity, the β-glucan and MP65 antigens in both purified and native forms. The MP65/bglu mAb is the first bispecific antibody generated against a fungal microorganism and may prove useful for the concurrent detection of different and clinically significant Candida biomarkers in patient sera.

Topics: Animals; Antibodies, Bispecific; Antibodies, Fungal; Antibodies, Monoclonal; Antibody Specificity; Antigens, Fungal; beta-Glucans; Biomarkers; Candida; Candida albicans; Candidiasis, Invasive; Fungal Proteins; Humans; Immunodominant Epitopes; Membrane Glycoproteins; Mice; Serologic Tests

To determine the effects of a strategy that uses serum (1,3)-β-d-glucan (BDG) results for antifungal treatment of ICU patients at high risk of invasive candidiasis.. Adult patients admitted to the ICU from January 2012 to June 2014 were included if they exhibited sepsis at the time of BDG testing and they met Candida score components ≥3. A retrospective analysis of collected data was performed.. In total, 198 patients were studied. Of 63 BDG-positive patients, 47 with candidaemia and 16 with probable Candida infection, all [31.8% (63/198)] received antifungal therapy. Of 135 BDG-negative patients, 110 [55.5% (110/198)] did not receive antifungal therapy, whereas 25 [12.6% (25/198)] were initially treated. Overall, antifungal therapy was started in 88 cases (44.4%), mostly with echinocandins. Antifungals were discontinued in 14 of 25 patients, as negative BDG results became available, and in 16 BDG-false-positive patients for whom subsequent findings allowed candidaemia (and other forms of invasive candidiasis) to be ruled out. Candidaemia was diagnosed only in one patient who did not receive prior antifungal therapy. The median antifungal therapy duration in candidaemic patients differed significantly from that in non-candidaemic patients [14 (IQR, 6-18) days versus 4 (IQR, 3-7) days; P < 0.001]. Using this approach, antifungal therapy was avoided in ∼73% of potentially treatable patients and it was shortened in another ∼20%.. This study supports the use of serum BDG results in the management of systemic antifungal drug prescription in septic patients. These findings need to be confirmed in additional studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candidiasis, Invasive; Critical Illness; Female; Humans; Male; Middle Aged; Proteoglycans; Retrospective Studies; Sepsis; Young Adult

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

Topics: Aged; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida; Candidiasis, Invasive; Female; Humans; Immunoglobulins; Intensive Care Units; Male; Middle Aged; Predictive Value of Tests; Proteoglycans; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Serum Albumin

Invasive candidiasis (IC) causes high morbidity and mortality rates after liver transplantation, in part due to delayed diagnosis. The fungal cell wall component (1,3)-beta-d-glucan (BG) could be an early biomarker of IC. This preliminary prospective study was designed to evaluate the contribution of BG measurements to the diagnosis of IC after liver transplantation. All consecutive patients who underwent liver transplantation at Henri Mondor Hospital in France between January and June 2013 were enrolled prospectively in the study. They were monitored weekly for colonization by Candida, and colonization index values were calculated. Serum samples were tested for BG (Fungitell; Cape Cod Inc.) at least weekly between liver transplantation and discharge from the hospital. A total of 52 patients (including 39 male patients) were enrolled, with a median age of 55 years (range, 31 to 69 years). The median Model for End-Stage Liver Disease (MELD) score was 27 (range, 6 to 40). Cultures from 42 patients (81%) yielded Candida spp., with the most common Candida species isolated being Candida glabrata (47%). Six cases of documented IC were found for four of the 52 patients. On the day the clinical diagnosis of IC was made, analysis based on combining two sequential BG-positive samples (>146 pg/ml) and a colonization index of ≥0.5 revealed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) results of 83%, 89%, 50%, and 97.6%, respectively. The detection of BG associated with Candida colonization may be a promising tool based on a high NPV that can rule out IC among high-risk patients.

Topics: Adult; Aged; beta-Glucans; Biomarkers; Candida; Candidiasis, Invasive; Female; France; Humans; Immunocompromised Host; Liver Transplantation; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Proteoglycans; Sensitivity and Specificity; Transplant Recipients

Serum 1,3-beta-d-glucan (BDG) testing is an established diagnostic marker for invasive fungal infections (IFI) among patients with haematological malignancies. In contrast limited data exist regarding the application of urine BDG testing. Same-day midstream urine and serum screening samples were collected in adult patients with underlying haematological malignancies. A total of 80 urine samples from 46 patients were investigated: Twenty-six had positive corresponding serum BDG >120 pg ml(-1), 27 intermediate (60-80 pg ml(-1)), and 27 negative serum BDG (<25 pg ml(-1)). A significant positive correlation between BDG in serum and urine samples was observed (P = 0.025; r = 0.252). Sensitivity, specificity, positive predictive value and negative predictive value (compared with same-day serum results) were: 42%, 76%, 46%, 73% when using an 80 pg ml(-1) urine cut-off, and 35%, 96%, 82%, 75% for a 250 pg ml(-1) cut-off. Urine BDG seemed to be higher in samples obtained from patients with probable IFI (n = 13, median 145, IQR 22-253) compared to those from patients without IFI (n = 56, median 24, IQR 15-88) but the difference was not significant (P = 0.069). Overall correlation of same-day urine BDG and serum BDG was moderate. However, urine BDG testing may warrant further investigation in larger studies, as high-positive urine results correlated with high-positive corresponding serum levels and clinical performance was comparable to serum BDG.

Topics: Adult; Aged; Aspergillosis; beta-Glucans; Candidiasis, Invasive; Clinical Chemistry Tests; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Predictive Value of Tests; Proteoglycans; Sensitivity and Specificity; Young Adult

To assess the performance of (1→3)-β-D-glucan (BDG) and Candida albicans germ tube antibody (CAGTA) for the diagnosis of invasive candidiasis (IC) in a prospective cohort of 107 unselected, non-neutropenic ICU patients.. BDG (cutoff positivity ≥80 pg/mL) and CAGTA (cutoff positivity ≥1/160) assays were performed twice a week. Confounding factors included amoxicillin-clavulanate and piperacillin-tazobactam treatments, recent surgery, Gram-positive bloodstream infection, renal replacement therapy, and enteral nutrition. Patients were classified as neither colonized nor infected (n = 29), Candida spp. colonization (n = 63) (low grade, n = 32; high grade, n = 31), and invasive candidiasis (IC) (n = 15).. BDG levels were higher in patients with IC and high-grade colonization than in the remaining groups (p = 0.012), and two consecutive measurements ≥80 pg/mL discriminated IC from the remaining groups (sensitivity 80%, specificity 75.7%). For the discrimination between IC and Candida spp. colonization, the AUC for the maximum value of BDG was 0.667 (95% CI 0.544-0.790) and for the maximum value of CAGTA 0.545 (95% CI 0.395-0.694). Significant changes of BDG and CAGTA kinetics in IC patients treated with antifungals were not observed. In patients neither colonized nor infected or with low-grade Candida spp. colonization, none of the confounding factors was associated with a significant increase in BDG positivity.. Two consecutive BDG levels ≥80 pg/mL allowed discrimination among IC and high-grade colonization. Systemic antifungal therapy could not be monitored with biomarker kinetics, and BDG levels were not subject to interference by confounding factors in either colonized or infected patients or with low-grade colonization.

Topics: Adult; Aged; Antibodies, Fungal; beta-Glucans; Biomarkers; Candida albicans; Candidiasis, Invasive; Cohort Studies; Female; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Sensitivity and Specificity; Spain

Colonization of patients occurs before development into invasive candidiasis. There is a need to determine the incidences of Candida colonization and infection in SICU patients, and evaluate the usefulness of beta-D-glucan (BDG) assay in diagnosing invasive candidiasis when patients are colonized.. Clinical data and fungal surveillance cultures in 28 patients were recorded from November 2010, and January to February 2011. Susceptibilities of Candida isolates to fluconazole, voriconazole, amphotericin B, micafungin, caspofungin and anidulafungin were tested via Etest. The utilities of BDG, Candida score and colonization index for candidiasis diagnosis were compared via ROC.. 30 BDG assays were performed in 28 patients. Four assay cases had concurrent colonization and infection; 23 had concurrent colonization and no infection; three had no concurrent colonization and infection. Of 136 surveillance swabs, 52 (38.24 %) were positive for Candida spp, with C. albicans being the commonest. Azole resistance was detected in C. albicans (7 %). C. glabrata and C. tropicalis were, respectively, 100 and 7 % SDD to fluconazole. All 3 tests showed high sensitivity of 75-100 % but poor specificity ranging 15.38-38.46 %. BDG performed the best (AUC of 0.89).. Despite that positive BDG is common in surgical patients with Candida spp colonization, BDG performed the best when compared to CI and CS.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candida albicans; Candida glabrata; Candidiasis; Candidiasis, Invasive; Carrier State; Caspofungin; Critical Care; Echinocandins; Female; Fluconazole; Humans; Incidence; Intensive Care Units; Lipopeptides; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Sensitivity and Specificity; Singapore; Tertiary Care Centers; Voriconazole

Initiation of empirical antifungal therapy for invasive candidiasis (IC) is usually based on clinical suspicion. Serological biomarkers have not yet been studied as a means of ruling out IC. We evaluated the potential role of two combined biomarkers in stopping unnecessary antifungals in patients at risk of IC in the ICU and in other wards.. This was a prospective observational study including adults starting empirical antifungal treatment for suspected IC, at Gregorio Marañón Hospital, Madrid (Spain). Patients were stratified according to admission department (ICU or other wards) and final diagnosis (no IC or proven or probable IC). Type of candidiasis (candidaemia or deep-seated candidiasis) was also considered. The Candida albicans germ tube antibody (CAGTA) test and the β-d-glucan (BDG) test were performed on serum samples collected by venepuncture on days 0, 3 and 5 after starting empirical antifungal therapy.. Sixty-three ICU patients and 37 non-ICU patients were included. High-risk gastrointestinal surgery and sepsis in non-surgical patients were the main indications for empirical treatment (30% each). Patients had no IC (58%), proven IC (30%) or probable IC (12%). Overall, sensitivity and negative predictive value of the combination of both the CAGTA test and the BDG test were 97% for the entire population. The best performance was observed in ICU patients (sensitivity and negative predictive value of 100%). Among patients without IC, all biomarkers were negative in 31 patients.. Serial determination of CAGTA/BDG during empirical antifungal therapy has a high sensitivity and negative predictive value. If properly confirmed, this strategy could be used to discontinue antifungal treatment in at least 31% of patients as a complementary tool in antifungal stewardship programmes.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Fungal; Antifungal Agents; beta-Glucans; Biomarkers; Candida albicans; Candidiasis, Invasive; Critical Care; Female; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Proteoglycans; Sensitivity and Specificity; Spain; Tertiary Care Centers

The current standard of treatment of invasive candidiasis with echinocandins requires once-daily therapy. To improve quality of life, reduce costs, and improve outcome, we studied the pharmacokinetics (PK), efficacy, and safety of alternate dosing regimens of micafungin (MFG) for the treatment of experimental subacute disseminated candidiasis.. MFG was administered for 12 days starting 24 hours after intravenous inoculation of 1 × 10(3) Candida albicans blastoconidia. Study groups consisted of MFG at 1 mg/kg every 24 hours (MFG1), 2 mg/kg every 48 hours (MFG2), and 3 mg/kg every 72 hours (MFG3), and untreated controls. PK of MFG were determined on day 7 by high-performance liquid chromatography and modeled using nonparametric adaptive grid program. A 2-compartment PK model with volume of the central compartment (Vc), clearance (SCL), and the intercompartmental rate constants Kcp and Kpc was used. The fungal burden in 7 tissues was determined 312 hours after the initiation of therapy.. PK of MFG were linear and the parameter means ± SD were Vc = 0.41 ± 0.18 L, Kcp = 2.80 ± 1.55/hour, Kpc = 1.71 ± 0.93/hour, and SCL = 0.16 ± 0.003 L/hour (r(2) = 0.99). The area under the plasma drug concentration - time curve for MFG1, MFG2, and MFG3 was 198.7 ± 19.8, 166.3 ± 36.7, and 192.8 ± 46.2 mg × hour/L, respectively (P = .24). All treatment groups showed significant and comparable resolution of (1→3)-β-D-glucan levels and clearance of C. albicans from liver, spleen, kidney, brain, lung, vitreous humor, and vena cava in comparison to untreated controls (P ≤ .05). There were no differences in hepatic or renal function among study groups.. Less fractionated MFG regimens of every 48 and 72 hours are safe and as effective in experimental disseminated candidiasis as once-daily therapy in neutropenic hosts.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida albicans; Candidiasis; Candidiasis, Invasive; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Echinocandins; Female; Lipopeptides; Micafungin; Neutropenia; Proteoglycans; Rabbits

Topics: beta-Glucans; Candidiasis, Invasive; Female; Humans; Male

Topics: beta-Glucans; Candidiasis, Invasive; Female; Humans; Male

Topics: Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Echinocandins; Female; Humans; Male

Topics: Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Echinocandins; Female; Humans; Male

We compared the rate and extent of anidulafungin's and fluconazole's activity in neutropenic and non-neutropenic mice with Candida albicans invasive candidiasis. In immunocompetent mice, anidulafungin significantly improved survival vs. controls and fluconazole, and significant reductions in (1→3)-β-D-glucan and fungal burden were observed. In neutropenic animals, the highest doses of anidulafungin (5 mg/kg) and fluconazole (10 mg/kg) also improved survival and reduced fungal burden. However, there were no differences in survival between these antifungals as anidulafungin's activity was attenuated in this model. These results demonstrate that the extent of anidulafungin in vivo efficacy may be dependent on host immune status.

Topics: Anidulafungin; Animals; Antifungal Agents; beta-Glucans; Blood; Blood Chemical Analysis; Candida albicans; Candidiasis, Invasive; Colony Count, Microbial; Disease Models, Animal; Echinocandins; Fluconazole; Mice; Mice, Inbred ICR; Neutropenia; Proteoglycans; Survival Analysis; Treatment Outcome

The kinetics of serum (1 → 3)-β-d-glucan (BG) following the diagnosis of invasive fungal disease and administration of antifungal therapy are poorly characterized. It is unknown whether early BG changes have prognostic implications. We assessed the post-diagnostic kinetics of BG in patients with an initial serum BG ≥80 pg/mL and at least one additional post-diagnostic BG value in the setting of invasive aspergillosis (IA, n=69), invasive candidiasis (IC, n=40), or Pneumocystis jirovecii pneumonia (PCP, n = 18), treated with antifungal therapy. Clinical failure of antifungal therapy and mortality were assessed at 6 and 12 weeks, and Cox modelling was used to assess the hazard of initial BG and change in BG at 1 or 2 weeks for these outcomes. In patients with at least two BG values, median initial BG was >500 pg/mL (interquartile range (IQR) 168 to >500; range 80 to >500) in IA, 136 pg/mL (IQR 88 to >500; range 31 to >500) in IC and >500 pg/mL (IQR 235 to >500; range 86 to >500) in PCP. In patients with at least two BG values through to 1 week after diagnosis, overall 1-week decline in BG was 0 pg/mL (IQR 0-53) in IA, 0 (IQR - 65 to 12) in IC and 17 (IQR 0-82) in PCP. Most patients with BG values through 6 and 12 weeks had persistent levels >80 pg/mL. Initial BG and the early trajectory of BG were not predictive of 6-week or 12-week clinical failure or mortality. Whereas BG eventually declines in patients with IA, IC and PCP, it lacks prognostic value within a clinically meaningful time frame.

Topics: Adult; Aged; Aged, 80 and over; Antifungal Agents; Antigens, Fungal; Aspergillosis; Aspergillus; beta-Glucans; Candida; Candidiasis, Invasive; Cause of Death; Female; Humans; Kinetics; Male; Middle Aged; Pneumocystis carinii; Pneumonia, Pneumocystis; Prognosis; Proteoglycans; Treatment Failure; Young Adult

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

The correlation of β-glucan (BG) levels with clinical outcomes in invasive candidiasis (IC) remains unknown. Patients with proven IC were followed prospectively from diagnosis to outcome with twice-weekly serum BG sampling. Correlation of BG with clinical outcome was assessed in each patient. BG levels tend to decrease in successfully treated patients and increase in treatment failures. BG levels may be useful as surrogates for outcome evaluation of IC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; beta-Glucans; Candidiasis, Invasive; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Serum; Treatment Outcome; Young Adult

Non-culture-based diagnostic strategies are needed for diagnosing invasive candidiasis (IC). We evaluated serial serum (1→3)-β-d-glucan (BG) levels in patients in the surgical trauma intensive care unit (SICU) patients with clinical evidence of IC. Serum samples from patients admitted to the SICU for a minimum of 3 days were collected twice weekly and analyzed for BG by using a Fungitell kit with a positive cutoff of ≥ 80 pg/ml. Diagnosis of IC was done using a set of predefined and validated clinical practice-based criteria. A total of 57 patients consented to participate and were enrolled. The median ICU stay was 16 days (range, 3 to 51). A total of 14 of 57 (25%) false positives were observed in the first sample (ICU day 3) and, overall, 73% of the day 3 samples had higher BG levels than subsequent samples. On the date of clinical diagnosis of IC, the sensitivity of a positive BG for identifying invasive candidiasis was 87%, with a 73% specificity. In patients with evidence of IC, the median BG value was significantly higher than those without evidence of IC (171 versus 48 pg/ml, P = 0.02), respectively. In the three patients with proven IC, BG was detected 4 to 8 days prior to diagnosis. BG serum detection may be a useful tool to aid in the early diagnosis of IC in SICU patients, particularly after day 3 and in patients with at least two positive samples drawn several days apart. Elevated BG levels within the first 3 days need to be further characterized.

Topics: Adolescent; Adult; Aged; beta-Glucans; Candidiasis, Invasive; Clinical Laboratory Techniques; Critical Care; Female; Humans; Male; Middle Aged; Proteoglycans; Sensitivity and Specificity; Young Adult