Mannan Antigen Research Articles

Regulatory Profile Changes of Lymphocytes and Peripheral Blood Monocytes in Children with Candidiasis Associated with Chronic Somatic Diseases

In this paper, we report results of the study of immune parameters with the assessment of regulatory and effector subpopulations of lymphocytes and monocytes with candidiasis in children with chronic somatic diseases (secondary pyelonephritis and obstructive diseases of the upper gastrointestinal tract). Candidiasis was diagnosed by the rising level of circulating Candida albicans mannan antigen and culture mycological research. It was found that the persistence of fungi is associated with differentiated regulatory changes in the structure of subpopulations of lymphocytes and monocytes with preferential increase of immunosuppressive cells (CD4+CD25+hi, CD3+CD16/56+, CD3−CD8+, CD3+4−8−) amid reduction of effector subpopulations of lymphocytes and antigen presenting cells associated with Th1 immune response profile.

English

Invasive Candida infections have emerged as an important pathogen in the last decade, especially in immunocompromized patients. The aim of the present study was to evaluate the detection of Candida species in blood samples from pediatric patients with sepsis by blood culture method versus antigen detection method by enzyme linked immunosorbent assay (ELISA) and molecular method by polymerase chain reaction (PCR). This cross-sectional study was carried out on children at Mansoura University Children Hospital (MUCH) with the presence of clinical signs suggesting sepsis with absence of prior antifungal therapy. Laboratory diagnosis included blood culture, mannan antigen detection of Candida species by ELISA and semi-nested PCR. Candida species were detected by blood culture in 15.6% of the children and was detected by PCR and antigen detection in 20% for each. Candidemia was more frequently detected among patients with central venous lines (38.5%), children with Diabetes Mellitus (DM) (23.1%) and children with frequent blood transfusions (15.4%). However, these risk factors were not statistically significant. Mortality rate among children with candidemia was 42.9%. The sensitivity, specificity, and accuracy of antigen detection method by ELISA compared to culture, were 71.4, 89.5 and 86.7%, respectively. The sensitivity, specificity and accuracy of semi-nested PCR compared to culture were 85.7, 92.1 and 91.1% respectively. It can be concluded from this study that Candida species is a frequent pathogen associated with pediatric sepsis. Blood culture though is a reliable laboratory method for its diagnosis may lack sensitivity and requires prolonged time. Semi-nested PCR for detection of candidemia is sensitive, specific and accurate method. Mannan antigen detection by ELISA is rapid and easy; however, it may lacks specificity; it can be used as a preliminary method for screening. Further studies are recommended to detect the appropriate laboratory algorithm for early diagnosis of candidemia to start antifungal therapy appropriately. Key words: Candida, Mannan antigen, polymerase chain reaction (PCR), blood culture.

Contribution of Candida biomarkers and DNA detection for the diagnosis of invasive candidiasis in ICU patients with severe abdominal conditions.

BackgroundTo assess the performance of Candida albicans germ tube antibody (CAGTA), (1 → 3)-ß-D-glucan (BDG), mannan antigen (mannan-Ag), anti-mannan antibodies (mannan-Ab), and Candida DNA for diagnosing invasive candidiasis (IC) in ICU patients with severe abdominal conditions (SAC).MethodsA prospective study of 233 non-neutropenic patients with SAC on ICU admission and expected stay ≥ 7 days. CAGTA (cutoff positivity ≥ 1/160), BDG (≥80, 100 and 200 pg/mL), mannan-Ag (≥60 pg/mL), mannan-Ab (≥10 UA/mL) were measured twice a week, and Candida DNA only in patients treated with systemic antifungals. IC diagnosis required positivities of two biomarkers in a single sample or positivities of any biomarker in two consecutive samples. Patients were classified as neither colonized nor infected (n = 48), Candida spp. colonization (n = 154) (low-grade, n = 130; high-grade, n = 24), and IC (n = 31) (intra-abdominal candidiasis, n = 20; candidemia, n = 11).ResultsThe combination of CAGTA and BDG positivities in a single sample or at least one of the two biomarkers positive in two consecutive samples showed 90.3 % (95 % CI 74.2–98.0) sensitivity, 42.1 % (95 % CI 35.2–98.8) specificity, and 96.6 % (95 % CI 90.5–98.8) negative predictive value. BDG positivities in two consecutive samples had 76.7 % (95 % CI 57.7–90.1) sensitivity and 57.2 % (95 % CI 49.9–64.3) specificity. Mannan-Ag, mannan-Ab, and Candida DNA individually or combined showed a low discriminating capacity.ConclusionsPositive Candida albicans germ tube antibody and (1 → 3)-ß-D-glucan in a single blood sample or (1 → 3)-ß-D-glucan positivity in two consecutive blood samples allowed discriminating invasive candidiasis from Candida spp. colonization in critically ill patients with severe abdominal conditions. These findings may be helpful to tailor empirical antifungal therapy in this patient population.

Specificity of mannan antigen and anti‐mannan antibody screening in patients with haematological malignancies at risk for fungal infection

Combination of mannan antigen and anti-mannan antibody (Mn/A-Mn) testing has been reported a useful and specific strategy for diagnosis of invasive Candida infections (ICIs). We evaluated Mn/A-Mn as a screening tool in patients with haematological malignancies. This clinical prospective study was performed at the Division of Hematology, Medical University Graz, Austria between July and December 2012. Patients at risk for fungal infection were included into the study and twice weekly screened by Mn/A-Mn testing, yielding 650 samples. Of overall 67 patients 66 had no evidence for ICI. From those, 153/640 serum samples (23.9%) were positive for mannan Ab, and nine (1.4%) for Ag. Most false positive Ab results were observed among 375 samples from patients without haematopoietic stem cell transplantation (34.9% resulted positive). Combined specificity of Mn/A-Mn was 74.8%. Of 10 samples obtained in the single patient with candidemia, five were positive for mannan Ag (from the day of diagnosis up to 40 days after detection of candidemia) and none for Ab. In conclusion, mannan Ab screening yielded a high number of false positive results. While mannan Ag was found to be highly specific and may have potential for diagnostic driven testing, mannan Ab testing cannot be recommended based on our study results.

Comparing immunological and molecular tests with conventional methods in diagnosis of acute invasive fungal rhinosinusitis

This study compared immunological and molecular testswith conventional methods in the diagnosis of acute invasive fungal rhinosinusitis. All tissue samples from maxillary sinuses were cultured and stained using periodic acid-Schiff. Two blood samples were cultured by bedside inoculation into BACTEC medium. Diagnostic tests were used: enzyme-linked immunosorbent assay for detection of galactomannan and mannan in serum samples, real-time PCR assays for Aspergillus spp. and Candida spp., and nested PCR for the Mucoraceae family. Among 31 immunocompromised patients, based on host factors, clinical, radiological and mycological findings, 18 patients were diagnosed with documented infection. By direct smear examination, 9 patients (50%) had positive results for Mucoraceae family, but only 5 samples showed growth in the culture (55.5%). Nested PCR results for species in this family were negative in all serum samples from patients. In addition, 9 patients had positive direct microscopic findings, of which 7 specimens produced positive growth for Aspergillus flavus (77.7%). The galactomannan test was positive in 6/9 (66.6%), and Aspergillus PCR were positive in 6 patients (66.6%). The isolated agent was C. albicans in one patient. The mannan antigen test to detect Candida was negative. None of the blood cultures was positive for fungal infection. The efficient method to diagnose fungal rhinosinusitis was direct microscopic examination of tissue samples. Immunological and molecular methods, which are available for some important fungi, can help clinicians with the diagnosis and management of infections in patients in critical condition when tissue sampling is not available.

Usefulness of Mannan Antigen and Risk Factors for Candidemia in Pediatric Patients in Mexico City

Usefulness of Mannan Antigen and Risk Factors for Candidemia in Pediatric Patients in Mexico City

Candida biomarkers in patients with candidaemia and bacteraemia

Microbiological strategies are necessary to help clinicians discontinue empirical antifungal therapy in patients with suspected invasive candidiasis. Culture methods and biomarkers each show low sensitivity. We analysed the value of combining different biomarkers as a decision-making tool for discontinuing empirical antifungal treatment. We studied stored serum samples from 31 patients with candidaemia (Candida albicans 40%, Candida tropicalis 20%, Candida parapsilosis 18%, Candida glabrata 12% and other 10%) and 50 patients with bacteraemia at Gregorio Marañón Hospital, Madrid, Spain. C. albicans germ tube antibody (CAGTA), mannan antigens (MN), antimannan antibodies (AMN) and (1→3)-β-d-glucan (BDG) were assayed using the manufacturer's and alternative cut-offs to improve the accuracy of the tests. The sensitivity of the biomarkers when used alone was low (58%-84%), but specificity was high (65.8%-92.0%). The best combinations were CAGTA and BDG using cut-offs of 1/80 and 80 pg/mL, respectively (sensitivity 96.8% and specificity 84%), and CAGTA and MN using cut-offs of 1/80 and 75 pg/mL, respectively (sensitivity 93.5% and specificity 86.0%). The sensitivity of both combinations was 100% for C. albicans, C. tropicalis and C. parapsilosis, but only combinations including BDG detected Candida krusei. The negative predictive values (NPVs) of both combinations were, respectively, 97.7% and 95.6% (prevalence of candidaemia, 23.6%). For a prevalence of candidaemia of 5% and 10%, the NPV reached 99.8% and 99.6%. The combinations of CAGTA and BDG or CAGTA and MN had a very high NPV at the alternative cut-offs and could be used in antifungal stewardship programmes as a decision-making tool for discontinuing unnecessary empirical therapy in patients with suspected candidaemia.

Humoral immune responses to Candida albicans complement receptor 3-related protein in the atopic subjects with vulvovaginal candidiasis. Novel sensitive marker for Candida infection.

In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral response against Candida CR3-RP. The most significant have been IgM and IgA isotype antibodies (33 and 47% positive cases, respectively). The quantitative evaluation of anti-CR3RP isotype antibodies was confronted with results of commercial ELISA anti-C. albicans antibodies diagnostics based on C. albicans cell wall mannan and β-glucan antigens, the most significant correlation being observed with anti-CR3-RP IgM and anti-β-D-glucan IgM (r(2) = 0.624) followed by isotype IgA (r(2) = 0.381). The immunogenicity and immunoreactivity of CR3RP antigen in RVC patients' sera had been evaluated with regard to the results reached by counterimmunoelectrophoresis and heterogeneous enzyme immunoassay. Obviously, synthetically prepared CR3-RP mimicking the Candida cell-wall-derived structure moiety represents a promising immunological tool not only for Candida serodiagnostics, but also prospectively for follow-up of targeted antifungal therapy and as promising Candida vaccine candidate.

Demonstration of β-1,2 mannan structures expressed on the cell wall of Candida albicans yeast form but not on the hyphal form by using monoclonal antibodies

Candida albicans is a polymorphic fungus that may be observed as both commensal and opportunistic pathogen in humans. As one of the major components of Candida cell wall structure, mannan plays an important role in the fungus-host cell interaction and in virulence. The ability to switch from yeast to hypha form of microorganism is crutial in the development of C.albicans infections. Hyphal form has different antigenic properties compared to yeast form and structural changes occur in the yeast cell wall during transition from yeast to hypha form. Although there are several factors associated with this transition process, sufficient information is not available. The aim of this study was to investigate the change of configuration in mannan structure found in C.albicans cell wall by using monoclonal antibodies. C.albicans (NIHA 207) serotype A strains were used as test strains throughout the study, together with Salmonella choleraesuis 211 and Salmonella infantis as controls with similar cell wall structures to that of C.albicans. Cultures were maintained on YPD-agar medium by incubating at 28°C for yeast forms, and on YPD-broth medium in a shaking incubator at 37°C for 3-4 hours for the growth of hyphal forms. Cells were harvested in the exponential phase, and after being washed, the mannan content from C.albicans were extracted from pellet by heating in 20 mM sodium citrate buffer for 90 minutes at 125°C. Hybridoma technique was used for the production of monoclonal antibodies. After immunizing the Balb/C mice with antigen, the splenocytes were harvested and fusion was performed between spleen cells and F0 myeloma cells. The clones grown in HAT medium were screened for the presence of antibody producing hybrid cells by ELISA method. The antibody isotypes were determined by using a commercial kit (Pierce Biotechnology, ABD). The culture supernatants which contained monoclonal antibodies were collected and purified according to the ammonium sulphate method. Sandwich ELISA and immunofluorescence (IF) methods have been used to detect the experimental reactions. In our study, highly specific class IgM murine monoclonal antibodies (mAb-2B7) against C.albicans yeast cell wall were obtained from clone 2B7. These antibodies cross-reacted with S.choleraesuis 211 and S.infantis bacteria sharing similar cell wall structure of C.albicans. The existence of mannan β-1,2 bonds on the surface of C.albicans yeast form was confirmed with a commercial monoclonal antibody (mAb-ACMK-1; Matriks Biotek(®), Turkey) specific for those bonds. Besides, mAb-ACMK-1 interacted with C.albicans yeast form and gave intense fluorescence (high positive reaction) in IF method, but no fluorescence (negative) was detected with hyphal form. This data, obtained for the first time with this study, indicates that the mannan β-1,2 bonds are either found infrequently or none in the fungal hyphal wall. Although both monoclonal antibodies recognize the mannan antigen, mAb-2B7 reacted with S.choleraesuis 211, while mAb-ACMK-1 did not, due to the difference of epitope specificity. In conclusion, monoclonal antibodies may facilitate the characterization of antigenic structures of Candida, which will lead for the identification of new determinants that may increase the sensitivity and specificity of commercial tests used for mannan detection in serum.

Invasive candidiasis serological diagnosis in solid organ transplant recipients.

Solid organ transplant recipients are at high risk of fungal infections, because of ongoing immunosuppressive treatment. There are three post organ transplant phases: early, intermediate, and late, all of them at risk of Candida infections. Since conventional tests are insufficient, specific secondary diagnostic tests are still being explored. Serological tests are currently the most common choice. The present study was to determine the usefulness of mannan antigen and anti-mannan antibody detection in diagnosing invasive candidiasis in liver or kidney transplant recipients. The levels of mannan and anti-mannan antibodies were assessed with Platelia Candida Ag Plus, and Platelia Candida Ab Plus (Biorad, Marne-la-Coquette, France) commercial tests, according to manufacturer's guidelines. Sixty six serum samples were obtained from 25 patients (9 liver transplant recipients, 7 kidney transplant recipients, and 9 patients prepared for a kidney transplant), 29 serum samples from 15 patients tested positive for mannan antigen. Serum samples were obtained from 14 patients tested positive for anti- mannan antibodies. Fungal antigen detection in blood serum in patients under immunosuppression, especially with neutropenia, suggests that antifungal treatment should be administered. Serological tests, especially mannan and anti-mannan ones, are very useful for confirmation or exclusion of invasive candidiasis in high-risk patients.

CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin.

CA-125 (coelomic epithelium-related antigen) forms the extracellular portion of transmembrane mucin 16 (MUC16). It is shed after proteolytic degradation. Due to structural heterogeneity, CA-125 ligand capacity and biological roles are not yet understood. In this study, we assessed CA-125 as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which is a C-type lectin showing specificity for mannosylated and fucosylated structures. It plays a role as a pattern recognition molecule for viral and bacterial glycans or as an adhesion receptor. We probed a human DC-SIGN-Fc chimera with CA-125 of fetal or cancer origin using solid- or fluid-phase binding and inhibition assays. The results showed that DC-SIGN binds to CA-125 of fetal origin and that this interaction is carbohydrate-dependent. By contrast, cancerderived CA-125 displayed negligible binding. Inhibition assays indicated differences in the potency of CA-125 to interfere with DC-SIGN binding to pathogen-related glycoconjugates, such as mannan and Helicobacter pylori antigens. The differences in ligand properties between CA-125 of fetal and cancer origin may be due to specificities of glycosylation. This might influence various functions of dendritic cells based on their subset diversity and maturation-related functional capacity.

Culture-negative Candida meningitis diagnosed by detection of Candida mannan antigen in CSF

We present a patient with chronic culture-negative Candida meningitis, in whom the diagnosis was made by detection of the mannan antigen (Mn) and anti-mannan antibodies (A-Mn) in the CSF.

Comparison of (1→3)-β- d -Glucan, Mannan/Anti-Mannan Antibodies, and Cand-Tec Candida Antigen as Serum Biomarkers for Candidemia

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.

Biomarkers for Diagnosis and Follow-Up of Invasive Candidiasis: A Brief Review of the ECIL Recommendations

The main biomarkers for rapid and non-invasive diagnosis of invasive candidiasis include 1,3-beta-D-glucan (BG), mannan antigen (Mn), anti-mannan antibodies (A-Mn) and various molecular methods. BG, Mn and A-Mn assays are standardized, and data on BG are the most extensive. For haematology and oncology population, its performance is characterised by suboptimal sensitivity but excellent specificity. For these populations, the experts from the third European Conference on Infections in Leukemia (ECIL-3) recommended BG for detection of invasive fungal infections with grading BII, and combined Mn/A-Mn detection for the diagnosis of candidemia and hepatosplenic candidiasis, with grading CII and BIII, respectively. While very promising, PCR lacks standardization and thus could not be formally recommended. There is limited and contradictory data on the performance of BG for the monitoring of outcome in patients with invasive candidiasis, although a trend of decline or increase of BG levels was found to be associated with, respectively, a successful response or failure.

A33 Is the presence of Candida Mannan antigen in bronchoalveolar lavage fluid of premature neonates correlated with the levels of α-defensins and S100 proteins?

A33 Is the presence of Candida Mannan antigen in bronchoalveolar lavage fluid of premature neonates correlated with the levels of α-defensins and S100 proteins?

Hacia el diagnóstico temprano de la candidiasis invasora en el paciente crítico

The management of invasive fungal infections in critically ill patients, from diagnosis to selection of the ther- apeutic protocol, is often a challenge. Early diagnosis and treatment are associated with a better prognosis, but apart from cases with positive cultures from blood or fluid/tissue biopsy, diagnosis is neither sensitive nor specific, and there is a need for specific markers in these diseases. Serodiagnostic assays such as mannan an-tigen, mannan antibodies, Candida albicans germ-tube antibodies or (1→3)-β-D-glucan detection, and mo-lecular techniques for the detection of fungal-specific DNA have been developed with promising results in critical care settings. One of the main features in diagnosis is the evaluation of risk factors for infection, which will identify patients in need of preemptive or empirical treatment. Clinical scores were built from those risk factors. The combination of prediction rules and non-culture microbiological tools could be currently be the key to improving the diagnosis and prognosis of invasive fungal infections in critically ill patients.

Biomarkers for Diagnosis of Candidal Infections

Candidemia and invasive candidiasis are associated with significant mortality, in part because of inadequate diagnostic tests. The current gold standard is blood culture, which is negative in 50% of cases. As such, development of novel diagnostics is a top priority. In Europe, studies of combined mannan antigen and anti-mannan antibody detection assays have demonstrated sensitivity of 71–100% and specificity of 86–93%. In the United States, there is more experience with (1 → 3)-β-D-glucan detection as a broad-spectrum assay for fungal pathogens. Sensitivity and specificity for diagnosing invasive candidiasis have ranged widely in studies (47–95% and 76–100%, respectively). Nucleic acid detection assays such as polymerase chain reaction (PCR) are potentially powerful tools that are now approaching the clinic. Overall, optimized PCR assays have sensitivities and specificities for candidemia and proven or probable invasive candidiasis that exceed 90%. Studies to determine the precise clinical roles of non–culture-based diagnostics are in progress.

Iliopsoas abscess caused by Aspergillus fumigatus complicated by pulmonary aspergillosis

We report a case of iliopsoas abscess caused by Aspergillus fumigatus with pulmonary complications. A 60-year-old man was admitted to the Showa University Hospital Department of Gastroenterology with fulminant hepatitis B on April 14, 2010, and treated with steroids. Although fulminant hepatitis B was improved by steroid and symptomatic therapy, he developed a fever on hospital day 39. The chest X-ray film showed a nodular lesion in the right middle-lower lung field, and both the (1→3)-β-D: -glucan and Candida mannan antigen tests were positive. The β-D: -glucan level increased despite treatment with fluconazole and other drugs, including low-dose micafungin. Abdominal computed tomography showed a low-density area in the right iliopsoas muscle. He was then referred to the Department of Clinical Infectious Diseases. A. fumigatus was isolated from the iliopsoas lesion and the pulmonary lesion after specimens were obtained by aspiration and bronchofiberscopy, respectively, leading to a diagnosis of fungal iliopsoas abscess. Steroid therapy was tapered early, the abscess was drained, and the micafungin dose was increased. This treatment led to improvement of the fever, inflammatory reaction, β-D: -glucan level, and lesions of the lung and iliopsoas muscle. In preparation for discharge, treatment was changed to voriconazole (parenteral→per oral) followed by itraconazole (per oral). His clinical course was satisfactory, and there was no recurrence after antifungal therapy was stopped. We conclude that after invasive pulmonary aspergillosis developed, A. fumigatus spread hematogenously to create an extremely rare iliopsoas abscess. The β-D: -glucan level closely reflected the response to treatment and was useful for follow-up.

Candida Colonization Index in Patients Admitted to an ICU

Multiple-site colonization with Candida spp. is commonly recognized as a risk factor for invasive fungal infection in critically ill patients. We carried out a study to determine the relationship between Candida colonization and invasive infection in neurological patients admitted to an ICU. At admission (T0) and every three days for two weeks, different samples (pharynx swab, tracheal secretions, stomach contents, etc.) were collected for mycological surveillance. Candida mannan antigen and Candida anti-mannan antibodies were assayed. The Colonization Index (CI) and Corrected Colonization Index were calculated for each time point. Of all patients 70% was already colonized by Candida spp. at T0 and six of them had CI ≥ 0.5. Three patients developed candidemia; they had CI ≥ 0.5 before infection. Positive values of Candida mannan antigen and anti-mannan antibodies were found only in the patients with candidemia. The sensitivity and specificity of the Candida mannan test were 66.6% and 100%, respectively, while the sensitivity and specificity of the anti-mannan antibody test were 100%. In accordance with other authors, we find the surveillance cultures are useful to monitor the Candida colonization in ICU patients. In addition, the sequential observation of anti-mannan antibodies could contribute to early diagnosis of candidiasis more than Candida mannan antigen in immunocompetent patients.

Diagnostic Performance of 1→3-β-D-Glucan in Neonatal and Pediatric Patients with Candidemia

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.