galactomannan and Candidiasis--Invasive

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

Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections.

Topics: Antifungal Agents; Aspergillus fumigatus; Candida; Candidiasis, Invasive; DNA, Fungal; Galactose; Humans; Mannans; Opportunistic Infections

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

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

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

Invasive fungal diseases (IFD) are a serious threat, but physicians in Asia lack access to many advanced diagnostics in mycology. It is likely that they face other impediments in the management of IFD. A gap analysis was performed to understand the challenges Asian physicians faced in medical mycology.. The Asia Fungal Working Group (AFWG) conducted a web-based survey on management practices for IFD among clinicians in China, India, Indonesia, Philippines, Singapore, Taiwan and Thailand.. Among 292 respondents, 51.7% were infectious disease (ID) specialists. Only 37% of respondents had received formal training in medical mycology. They handled only around 2-4 proven cases of each fungal infection monthly, with invasive candidiasis the most common. For laboratory support, the majority had access to direct microscopy (96%) and histopathology (87%), but galactomannan and azole levels were available to 60% and 25% of respondents, respectively. The majority (84%) used clinical parameters for treatment response monitoring, and 77% followed the Infectious Diseases Society of America guidelines. The majority (84%) did not use the services of an ID physician. Where febrile neutropenia was concerned, 74% of respondents used the empirical approach. Only 30% had an antifungal stewardship program in their hospital. Eighty percent could not use preferred antifungals because of cost.. The survey identified inadequacies in medical mycology training, non-culture diagnostics, access to antifungal drugs, and local guidelines as the major gaps in the management of IFDs in Asian countries. These gaps are targets for improvement.

Topics: Antifungal Agents; Candidiasis, Invasive; China; Clinical Competence; Education, Medical; Galactose; Humans; India; Indonesia; Invasive Fungal Infections; Mannans; Mycology; Philippines; Singapore; Surveys and Questionnaires; Taiwan; Thailand

Topics: Candidiasis, Invasive; Critical Care; Galactose; Humans; Invasive Pulmonary Aspergillosis; Mannans; Polymerase Chain Reaction; Serology; Societies, Medical; United States