Search Results (7)

Invasive candidiasis, including bloodstream infection (candidemia), encompasses the most severe forms of Candida infection. Several species-specific and non-specific serological assays are commercially available to aid in diagnosis. This study compared the performance of five such biomarker assays. Serum samples from 14 patients with proven or probable invasive candidiasis, and from 10 control patients, were included in the analysis. A total of 50 serum samples were tested using C. albicans germ tube antibody (CAGTA) assay (Vircell), C. albicans IgM, C. albicans IgG and Candida mannan assays (Dynamiker Biotechnology). Among these samples, the β-1-3-D-glucan (BDG) assay (Fungitell), a laboratory standard for the diagnosis of invasive candidiasis, was positive in 20 (40%), intermediate in five (10%) and negative in 25 (50%). In cases of proven or probable candidemia, the sensitivity and specificity of the BDG assay was 86% and 80%, respectively; the Candida mannan assay, 14% and 86%; the CAGTA test, 57% and 60%; the C. albicans IgM assay, 71% and 60%; and C. albicans IgG assay 29% and 90%. In 4/8 (50%) cases with multiple serum samples, C. albicans IgM was positive sooner than BDG. Thus, when used as a rule-out test for invasive candidiasis, our data suggest that the C. albicans IgM assay may assist antifungal stewardship (over serum BDG). Full article

Serum 1,3-β-d-glucan(BDG) is a broad fungal biomarker for invasive fungal disease (IFD). More data is still required to support the Fujifilm Wako assay as a valuable alternative to the widely used Fungitell assay. We included archived serum samples from 157 individuals (97 cases; 33-IA, 64-IC, and 60 controls) for the comparative performance evaluation of the Fungitell assay and the Fujifilm Wako assay for IFD diagnosis. The BDG value was significantly higher in patients with IFD vs. controls (70.79 pg/mL vs. 3.03 pg/mL, p: 0.0002). An area under the curve (AUC) for the IFD, IC, and IA diagnosis was 0.895, 0.910, and 0.866, respectively, for the Fujifilm Wako assay. Based on the highest Youden’s index (0.667), a cutoff of 5 pg/mL was selected as the optimum for the Fujifilm Wako assay with good sensitivity (79.4%), specificity (88.3%) and agreement (84.7%, Cohen’s k:0.691) with the Fungitell assay. The mean run-time of the Fujifilm Wako assay was 70.12 min, and real-time observation allowed earlier time to result in Fujifilm Wako vs. Fungitell assay (37 vs. 120 min, p: < 0.0001). Thus, our findings support the diagnostic value of the Fujifilm Wako assay for the diagnosis of IFD. However, there is still a need to validate diagnostic protocols to optimize their use in multi-centre studies with different patient groups. Full article

(1-3)-beta-D-glucan (BDG) is an almost panfungal marker (absent in zygomycetes and most cryptococci), which can be successfully used in screening and diagnostic testing in patients with haematological malignancies if its advantages and limitations are known. The aim of this review is to report the data, particularly from the last 5 years, on the use of BDG in haematological population. Published data report mainly on the performance of the Fungitell™ assay, although several others are currently available, and they vary in method and cut-off of positivity. The sensitivity of BDG for invasive fungal disease (IFD) in haematology patients seems lower than in other populations, possibly because of the type of IFD (lower sensitivity was found in case of aspergillosis compared to candidiasis and pneumocystosis) or the use of prophylaxis. The specificity of the test can be improved by using two consecutive positive assays and avoiding testing in the case of the concomitant presence of factors associated with false positive results. BDG should be used in combination with clinical assessment and other diagnostic tests, both radiological and mycological, to provide maximum information. Good performance of BDG in cerebrospinal fluid (CSF) has been reported. BDG is a useful diagnostic method in haematology patients, particularly for pneumocystosis or initial diagnosis of invasive fungal infections. Full article

Understanding the potential contamination of pharmaceutical products with innate immunity modulating impurities (IIMIs) is essential for establishing their safety profiles. IIMIs are a large family of molecules with diverse compositions and structures that contribute to the immune-mediated adverse effects (IMAE) of drug products. Pyrogenicity (the ability to induce fever) and activation of innate immune responses underlying both acute toxicities (e.g., anaphylactoid reactions or pseudoallergy, cytokine storm) and long-term effects (e.g., immunogenicity) are among the IMAE commonly related to IIMI contamination. Endotoxins of gram-negative bacteria are the best-studied IIMIs in that both methodologies for and pitfalls in their detection and quantification are well established. Additionally, regulatory guidance documents and research papers from laboratories worldwide are available on endotoxins. However, less information is currently known about other IIMIs. Herein, we focus on one such IIMI, namely, beta-glucans, and review literature and discuss the experience of the Nanotechnology Characterization Lab (NCL) with the detection of beta-glucans in nanotechnology-based drug products. Full article

Blood salvage techniques are increasingly being used during surgical procedures to reduce the need for exogenous blood products. The blood recovered from the surgical field through aspiration or absorption by surgical sponges is reinfused into a patient. A 65-year old patient who underwent coronary artery bypass grafting using blood salvage techniques developed a fever on post-op day 3 and was noted to have an elevated β-d-glucan level, a marker of systemic fungal infections. Ultimately, no fungal infection was identified, β-d-glucan levels slowly decreased and the patient demonstrated clinical improvement. To determine whether blood salvage procedures led to his elevated β-d-glucan levels, the surgical sponges were tested for elutable levels of β-d-glucan. The β-d-glucan content of the eluents was measured using the Fungitell® IVD kit (Associates of Cape Cod, Inc.; East Falmouth, MA). The β-d-glucan levels were found to be in concentrations 10,000-times greater than the limit of detection for human serum. While various studies have demonstrated both the immunomodulatory and pro-inflammatory effects of β-d-glucan, the physiologic impact of such high levels of β-d-glucan post-operatively remains unknown. Additionally, the persistence of detectable β-d-glucan up to several weeks after surgical procedures presents a challenge for the diagnosis of invasive fungal infections. Further studies are needed to assess the beta-glucanemia-related safety of surgical materials and their potential biological effects. Full article

Invasive fungal infections (IFI) are complications after liver transplantation involving high morbidity and mortality. (1,3)-β-d-glucan (BG) is a biomarker for IFI, but its utility remains uncertain. This study was designed to evaluate the impact of BG following their diagnosis. Between January 2013 and May 2016, 271 liver transplants were performed in our institution. Serum samples were tested for BG (Fungitell^®, Associates Cape Code Inc., Falmouth, MA, USA) at least weekly between liver transplantation and the discharge of patients. Nineteen patients (7%) were diagnosed with IFI, including 13 cases of invasive candidiasis (IC), eight cases of invasive pulmonary aspergillosis, and one case of septic arthritis due to Scedosporium apiospernum. Using a single BG sample for the primary analysis of IFI, 95% (21/22) of the subjects had positive BG (>80 pg/mL) at the time of IFI diagnosis. The area under the ROC curves to predict IFI was 0.78 (95% CI: 0.73–0.83). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of BG for IFI were 75% (95% CI: 65–83), 65% (62–68), 17% (13–21), and 96% (94–97), respectively. Based on their high NPV, the BG test appears to constitute a good biomarker to rule out a diagnosis of IFI. Full article

Mortality rates due to invasive candidiasis remain unacceptably high, in part because the poor sensitivity and slow turn-around time of cultures delay the initiation of antifungal treatment. β-d-glucan (Fungitell) and polymerase chain reaction (PCR)-based (T2Candida) assays are FDA-approved adjuncts to cultures for diagnosing invasive candidiasis, but their clinical roles are unclear. We propose a Bayesian framework for interpreting non-culture test results and developing rational patient management strategies, which considers test performance and types of invasive candidiasis that are most common in various patient populations. β-d-glucan sensitivity/specificity for candidemia and intra-abdominal candidiasis is ~80%/80% and ~60%/75%, respectively. In settings with 1%–10% likelihood of candidemia, anticipated β-d-glucan positive and negative predictive values are ~4%–31% and ≥97%, respectively. Corresponding values in settings with 3%–30% likelihood of intra-abdominal candidiasis are ~7%–51% and ~78%–98%. β-d-glucan is predicted to be useful in guiding antifungal treatment for wide ranges of populations at-risk for candidemia (incidence ~5%–40%) or intra-abdominal candidiasis (~7%–20%). Validated PCR-based assays should broaden windows to include populations at lower-risk for candidemia (incidence ≥~2%) and higher-risk for intra-abdominal candidiasis (up to ~40%). In the management of individual patients, non-culture tests may also have value outside of these windows. The proposals we put forth are not definitive treatment guidelines, but rather represent starting points for clinical trial design and debate by the infectious diseases community. The principles presented here will be applicable to other assays as they enter the clinic, and to existing assays as more data become available from different populations. Full article