epiglucan and posaconazole

An established diagnosis of invasive aspergillus is seldom achieved premortem. Conventional laboratory diagnostic methods such as culture and microscopy, although very useful when positive, are insensitive and time-consuming, resulting in late diagnosis and treatment and contributing to high mortality rates. As a result, routine antifungal prophylaxis and early empirical treatment have been recommended. The use of sensitive and rapid non-culture-based diagnostic assays for the detection of Aspergillus antigens (using commercially available tests to detect galactomannan and 1, 3 β-D-glucan) or detection of genomic DNA sequences may allow a shift in emphasis from empirical to preemptive therapy, especially when substantiated by suggestive radiological findings. These new tools may be used to confirm a presumed diagnosis of invasive aspergillosis, or, when used to screen high-risk patients, may identify an infection at an early stage of disease. Their excellent negative predictive value should convince clinicians to withhold antifungal therapy in patients with no other signs of fungal disease. On the other hand, consecutive positive results should at least trigger a complete diagnostic workup. This article will review the diagnostic utility as well as the pitfalls of using these non-culture-based tools for diagnosing invasive aspergillosis.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Bronchoalveolar Lavage Fluid; Galactose; Humans; Mannans; Proteoglycans; Triazoles; Voriconazole

Management of invasive mold infections in patients with prolonged neutropenia and hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) has been hampered by the difficulty in diagnosing these infections. Definite diagnosis invariably centers on histologic identification of hyphae in tissue or on culture from a sterile body site. Therefore, most practitioners have relied on prophylaxis and empiric therapy. Currently, emphasis is shifting from routine prophylaxis and empiric therapy to screening of patients with neutropenia at high risk so that clinicians can administer appropriate antifungal therapy early, when it can potentially improve patient outcome. Non-culture-based microbiologic tools are at the forefront of this paradigm shift. Commercially available methods to detect fungal antigens and sophisticated techniques to detect fungal DNA may be used as screening tools during the highest risk period. Together with assessment of clinical signs, cultures, and especially CT scanning, these methods are useful for starting antifungal therapy preemptively. While awaiting further evaluation of these tools during the postengraftment period of allogeneic HSCT, mold-active prophylaxis targeting the subgroup of patients with severe acute or chronic GVHD may be justified. However, some critical issues have not yet been adequately addressed, including the generalizability of study results, impact of mucositis and gastrointestinal GVHD on drug bioavailability, need for therapeutic drug monitoring, impact of prophylaxis on the performance of diagnostic assays, and optimal treatment of breakthrough invasive fungal infections.

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; beta-Glucans; Enzyme-Linked Immunosorbent Assay; Humans; Immunocompromised Host; Mycoses; Neoplasms; Neutropenia; Proteoglycans; Risk Assessment; Tomography, X-Ray Computed; Triazoles

Here, we present a case of an immunocompetent 37-year old male who developed Aspergillus fumigatus osteomyelitis 16 years after extensive chest wall reconstructive surgery for Ewing sarcoma. His treatment course was complicated by a severe adverse drug reaction to voriconazole, requiring the use of oral posaconazole therapy. Serum 1,3-beta-D glucan assay was utilized to dictate the duration of posaconazole therapy. The patient successfully completed 9 months of oral posaconazole therapy and has not had clinical recurrence for 9 months off antifungal therapy.

Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Baltimore; beta-Glucans; Humans; Male; Osteomyelitis; Treatment Outcome; Triazoles

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Cytarabine; Daunorubicin; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Pulmonary Aspergillosis; Retrospective Studies; Risk Factors; Triazoles; Vidarabine

The in vitro activity of posaconazole (PSC) and voriconazole (VRC) was tested by using time-kill studies against 3 strains of Candida lusitaniae. Both drugs showed fungistatic activity against all strains. The efficacy of those compounds was evaluated by reducing kidney fungal burden and by determining (1→3)-β-d-glucan serum levels in a murine model of invasive infection of C. lusitaniae. The therapies tested were VRC at 10, 25, or 40 mg/kg/day and PSC at 5, 12.5, or 20 mg/kg/twice a day. All the dosages showed efficacy in a dose-dependant manner being high doses of both antifungals able to sterilize some kidneys after 10 days. With the exception of the strain FMR 9474, against which PSC was more effective than VRC, no differences in reducing tissue burden were found between the treatments. All doses of both antifungals were able to significantly reduce (1→3)-β-d-glucan serum levels with no significant differences between treatments and between the same doses of both drugs.

Topics: Animals; Antifungal Agents; beta-Glucans; Candida; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Kidney; Male; Mice; Proteoglycans; Treatment Outcome; Triazoles; Voriconazole

The fungus Saprochaete capitata causes opportunistic human infections, mainly in immunocompromised patients with hematological malignancies. The best therapy for this severe infection is still unknown. We evaluated the in vitro killing activity and the in vivo efficacy of posaconazole at 5, 10, or 20 mg/kg twice a day (BID) in a murine neutropenic model of systemic infection with S. capitata by testing a set of six clinical isolates. Posaconazole showed fungistatic activity against all of the isolates tested. The different doses of the drug, especially the highest one, showed good efficacy, measured by prolonged survival, reduction of (1-3)-β-D-glucan levels in serum, tissue burden reduction, and histopathology.

Topics: Animals; Antifungal Agents; Basidiomycota; beta-Glucans; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Immunocompromised Host; Kidney; Male; Mice, Inbred Strains; Microbial Sensitivity Tests; Mycoses; Neutropenia; Proteoglycans; Triazoles

Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined.. We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6-132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (<65 months since first symptoms), negative serum BG and PET/CT normalization.. MRI, PET/CT and serum BG appear as promising tools to assess optimal time of antifungal treatment for eumycetoma.

Topics: Adolescent; Adult; Antifungal Agents; beta-Glucans; Child; Exophiala; Fluorodeoxyglucose F18; Fusarium; Humans; Madurella; Magnetic Resonance Imaging; Male; Mycetoma; Positron-Emission Tomography; Proteoglycans; Retrospective Studies; Skin; Treatment Outcome; Triazoles; Voriconazole; Young Adult

Topics: Antifungal Agents; Antigens, Fungal; Aspergillosis; beta-Glucans; Candidiasis; Chemoprevention; Humans; Leukemia; Proteoglycans; Triazoles