laminaran and Fungemia

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

Topics: Anidulafungin; Antifungal Agents; Aspergillosis; beta-Glucans; Candidiasis; Clinical Trials as Topic; Critical Care; Diabetes Complications; Disease Susceptibility; Echinocandins; Fungemia; Galactose; Hematologic Diseases; Humans; Immunocompromised Host; Mannans; Meta-Analysis as Topic; Mycoses; Neoplasms; Opportunistic Infections

Topics: Anidulafungin; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Caspofungin; Cross Infection; Echinocandins; Fungemia; Humans; Infusions, Intravenous; Lipopeptides; Lipoproteins; Male; Micafungin; Microbial Sensitivity Tests; Middle Aged; Neutropenia; Peptides, Cyclic; Practice Guidelines as Topic

The dramatic increase in nosocomial invasive mycoses over the past two decades has led to increased interest in the area of antifungal development. Unfortunately, the infusion of new diagnostic technology into the clinical mycology laboratory has lagged behind. Although newer, automated, continuous-monitoring blood culture systems are as sensitive as the older, manual "gold standard" system, the recovery of fungi from blood, as well as other clinical specimens, remains an insensitive marker for invasive fungal infection. Antigen assays for the rapid diagnosis of invasive fungal infections are in development, and galactomannan and glucan are two such promising antigens. Glucan may be present in the blood of patients with infection secondary to a wide variety of fungal pathogens, including Candida, Aspergillus, Fusarium, Saccharomyces, Trichosporon and Acremonium species. Early data suggest galactomannan may be present in the blood in detectable levels very early in the course of invasive aspergillosis. The galactomannan assay currently undergoing evaluations may actually be positive prior to the clinical suspicion for infection and may be useful in monitoring therapeutic response as well; however, the etiology of false-positive results following cytotoxic chemotherapy still has to be elucidated. PCR assays are also being developed in the research laboratory, however, the PCR assays will require a significant amount of adaptation and validation before they are ready for clinical care. Well-planned studies to evaluate the performance characteristics as well as appropriate clinical and cost-effective application of these new tests are needed.

Topics: Antigens, Fungal; Aspergillosis; beta-Glucans; Biotechnology; Candidiasis; Centrifugation; Culture Media; Enzyme-Linked Immunosorbent Assay; Fungemia; Glucans; Humans; Immunocompromised Host; Mannans; Medical Laboratory Science; Membrane Glycoproteins; Mycoses; Polymerase Chain Reaction

The usefulness to diagnose and monitor invasive candidiasis (IC) using beta-glucan (BG) and antibodies against Candida albicans germ tubes (CAGT) was evaluated in a twice-weekly screening of 35 episodes in neutropenic adults at high risk. Three proven IC and three probable IC were assessed. Diagnostic levels of both markers were detected in 100% of proven IC and in 66% of probable IC. Sensitivity, specificity, positive and negative predictive values of BG and anti-CAGT antibodies detection were 83.3%, 89.6%, 62.5% and 96.3%, and 83.3%, 86.2%, 55.5%, 96.1%, respectively. False positive reactions occurred at a rate of 10.3% and 13.8% for the detection of BG and anti-CAGT antibodies, respectively. However, the patients with false positive results were different by each test. Both tests anticipated the clinical and radiological diagnosis, and the initiation of antifungal therapy in most patients. Combination of both tests improved specificity and positive predictive value to 100%.

Topics: Adolescent; Adult; Aged; Amphotericin B; Anemia, Aplastic; Antibodies, Fungal; Antibody Specificity; Antifungal Agents; Antigens, Fungal; beta-Glucans; Candida albicans; Candidiasis; False Positive Reactions; Female; Fluconazole; Fungemia; Hematologic Neoplasms; Hepatitis; Humans; Liposomes; Male; Middle Aged; Neutropenia; Patient Isolation; Predictive Value of Tests; Sensitivity and Specificity

(1-->3)-beta-D-Glucan is one of the major structural components of fungi, and it seems that it can be detected by the fractionated (1-->3)-beta-D-glucan-sensitive component from a Limulus lysate, factor G. We evaluated the concentration of (1-->3)-beta-D-glucan by using factor G and other fungal antigens in 24 patients with clinical evidence of mycosis and 36 healthy subjects. The mean concentration of (1-->3)-beta-D-glucan in the plasma of the healthy subjects was found to be 2.7 +/- 1.9 pg/ml (range, < 6.9 pg/ml), and it was found to be substantially higher in all 11 patients with candidemia (mean, 2,207.4 pg/ml; range, 325.4 to 8,449.0 pg/ml). Eight of those 11 patients with candidemia (73%) were positive for the Cand-Tec heat-labile candida antigen and only 3 patients (27%) were positive for mannan antigen. Three patients with invasive pulmonary aspergillosis were positive for galactomannan and had, in addition, high concentrations of (1-->3)-beta-D-glucan (mean, 323.3 pg/ml; range, 27.0 to 894.0 pg/ml). All 10 patients with cryptococcosis (including 2 patients with probable cryptococcosis) were positive for cryptococcal antigen by the Eiken latex test; however, (1-->3)-beta-D-glucan levels were not elevated in these patients (mean, 7.0 pg/ml; range, < 16.5 pg/ml). Our results indicated that (1-->3)-beta-D-glucan levels are elevated in patients with candidiasis and aspergillosis but not in those with cryptococcosis.

Topics: Adult; Antigens, Fungal; Aspergillosis; beta-Glucans; Candidiasis; Cryptococcosis; Female; Fungemia; Galactose; Glucans; Humans; Limulus Test; Male; Mannans; Middle Aged; Serologic Tests

We evaluated the clinical usefulness of a polymerase chain reaction (PCR) assay amplifying the 18S ribosomal RNA gene of fungi for the diagnosis of deep candidiasis, compared with that of the beta-glucan test or Cand-Tec test. Thirty critically ill patients who had received prolonged care with intravenous hyperalimentation and endotracheal intubation in the intensive care unit and were suspected of having deep fungal infections were examined. Twenty-one were fungi positive in the PCR assay (70%). Among 24 samples in which the PCR assay, beta-glucan test and Cand-Tec test were performed simultaneously, 75% of the samples (18/24) were fungi positive in the PCR assay, whereas only 54% (13/24) had positive reactions in the beta-glucan test and 21% (5/24) in the Cand-Tec test. The results of the Cand-Tec test showed no relationship with those of the PCR or beta-glucan test. The lower limit of detection in the PCR assay was 4-5 CFU/ml of C. albicans in blood. No fungal organism was amplified from the serum of 20 healthy individuals. The results of the PCR assay and beta-glucan test showed a significant correlation in this study, but the PCR assay proved to be more sensitive than the beta-glucan test (p < 0.05), and to be more useful for the clinical diagnosis and monitoring of deep Candidiasis.

Topics: beta-Glucans; Candida; Candidiasis; Colony Count, Microbial; DNA Primers; DNA, Fungal; Electrophoresis, Agar Gel; Female; Fungemia; Genes, Fungal; Glucans; Humans; Male; Polymerase Chain Reaction; Reproducibility of Results; RNA, Fungal; RNA, Ribosomal, 18S; Sensitivity and Specificity

The present multicentre clinical study was conducted to assess the clinical utility of a new diagnostic method for deep mycosis in which (1-->3)-beta-D-glucan, a fungal cell wall component existing in plasma, was quantitatively measured by the kinetic turbidimetric Limulus test (WB003). Plasma (1-->3)-beta-D-glucan concentrations were 0.57 +/- 0.10 microgram/l in 92 healthy subjects and 0.62 +/- 0.32 microgram/l in 26 patients with non-mycotic diseases (disease control group). In comparison with these healthy subjects and patients with non-mycotic diseases, patients with mycosis had significantly higher plasma (1-->3)-beta-D-glucan concentrations: 19.63 +/- 73.28 micrograms/l in 12 patients with candidaemia, 11.28 +/- 21.42 micrograms/l in 7 patients with urinary Candida infection, 4.84 +/- 12.71 micrograms/l in 5 patients with pulmonary candidiasis, and 12.21 +/- 31.31 micrograms/l in 4 patients with invasive pulmonary aspergillosis. On the statistical analysis of these data, a cut-off value was set at 1.0 microgram/l. Using this cut-off value, 3 patients with pulmonary cryptococcosis and 4 patients (4/6) with pulmonary aspergilloma were all negative with low plasma (1-->3-beta-D-glucan levels. The test WB003 provided equivalent or higher efficiency of diagnosis of candidiasis and aspergillosis, in comparison with commercially available antigen detection kits, demonstrating its utility as a diagnostic reagent. It may also be useful in assessing therapeutic effectiveness when used periodically after treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Candidiasis; Cryptococcosis; Diagnostic Errors; Evaluation Studies as Topic; Female; Fungemia; Glucans; Humans; Kinetics; Limulus Test; Lung Diseases, Fungal; Male; Middle Aged; Mycoses; Nephelometry and Turbidimetry; Time Factors; Urinary Tract Infections

(1-->3)-beta-D-glucan is a characteristic fungal cell-wall constituent. To assess the clinical usefulness of this glucan in screening for invasive fungal infection or fungal febrile episodes, we measured the plasma concentration at the time of routine blood culture in 202 febrile episodes by means of factor G, a horseshoe-crab coagulation enzyme that is extremely sensitive to this polysaccharide. With a plasma cut-off value of 20 pg/mL, 37 of 41 episodes of definite fungal infections (confirmed at necropsy or by microbiology) had positive results (sensitivity 90%). All of 59 episodes of non-fungal infections, tumour fever, or collagen diseases had concentrations below the cut-off value (specificity 100%). Of 102 episodes of fever of unknown origin, 26 had plasma glucan concentrations of more than 20 pg/mL. With those 102 cases taken as non-fungal infections, the positive predictive value of the test was estimated as 59% (37/63), the negative predictive value as 97% (135/139), and the efficiency as 85% (172/202). The positive predictive value should improve if there were a sensitive gold standard that could discriminate fungal from non-fungal infections. Causative fungi included candida, aspergillus, cryptococcus, and trichosporon. Determination of plasma (1-->3)-beta-D-glucan with factor G is a highly sensitive and specific test for invasive deep mycosis and fungal febrile episodes, and will substantially benefit immunocompromised patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; beta-Glucans; Blood Coagulation Factors; Candidiasis; Child; Child, Preschool; Female; Fever; Fungemia; Glucans; Humans; Male; Middle Aged; Mycoses; Sensitivity and Specificity; Serine Endopeptidases