galactomannan and Mucormycosis

Mucormycosis generally develops under immunocompromised conditions, including hematological malignancies and solid organ or hematopoietic stem cell transplantation. Although mucormycosis usually affects the lungs and paranasal sinuses, sporadic cases of invasive mucormycosis of the liver have been reported. We hereby report a patient with myelofibrosis who developed hepatic mucormycosis diagnosed by post-mortem examination. An extensive literature review identified 13 reported cases of hepatic mucormycosis, including ours, without lung involvement. Most of the underlying diseases or conditions were hematological malignancies and solid organ transplantation. Three cases had splenic lesions and four had gastrointestinal lesions, suggesting the possibility of translocation to the liver and/or spleen from the gastrointestinal tracts. Hepatic mucormycosis should be recognized as one of the presentations of invasive mucormycosis, especially when hepatic nodules are found in immunocompromised patients such as those with hematological malignancy or recipients of solid organ transplantation.

Topics: Aged; Amphotericin B; Antifungal Agents; Autopsy; Fatal Outcome; Ferritins; Galactose; Humans; Invasive Fungal Infections; Liver Diseases; Male; Mannans; Mucormycosis; Primary Myelofibrosis; Spleen

Invasive mould infections (IMIs), such as invasive aspergillosis or mucormycosis, are a major cause of death in patients with haematological cancer and in patients receiving long-term immunosuppressive therapy. Early diagnosis and prompt initiation of antifungal therapy are crucial steps in the management of patients with IMI. The diagnosis of IMI remains a major challenge, with an increased spectrum of fungal pathogens and a diversity of clinical and radiological presentations within the expanding spectrum of immunocompromised hosts. Diagnosis is difficult to establish and is expressed on a scale of probability (proven, probable and possible). Imaging (CT scan), microbiological tools (direct examination, culture, PCR, fungal biomarkers) and histopathology are the pillars of the diagnostic work-up of IMI. None of the currently available diagnostic tests provides sufficient sensitivity and specificity alone, so the optimal approach relies on a combination of multiple diagnostic strategies, including imaging, fungal biomarkers (galactomannan and 1,3-β-d-glucan) and molecular tools. In recent years, the development of PCR for filamentous fungi (primarily Aspergillus or Mucorales) and the progress made in the standardization of fungal PCR technology, may lead to future advances in the field. The appropriate diagnostic approach for IMI should be individualized to each centre, taking into account the local epidemiology of IMI and the availability of diagnostic tests.

Topics: Aspergillosis; Aspergillus fumigatus; beta-Glucans; Early Diagnosis; Galactose; Hematologic Neoplasms; Humans; Immunocompromised Host; Immunosuppression Therapy; Invasive Fungal Infections; Magnetic Resonance Imaging; Mannans; Mucor; Mucormycosis; Organ Transplantation; Polymerase Chain Reaction; Positron Emission Tomography Computed Tomography; Tomography, X-Ray Computed

Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing conditions, e.g. corticosteroid treatment, chronic obstructive pulmonary disease, liver cirrhosis, solid organ cancer, HIV infection and transplantation. Diagnosis is challenging because the signs and symptoms are non-specific, and initiation of additional diagnostic examinations is often delayed because clinical suspicion is low. Isolation of an Aspergillus species from the respiratory tract in critically ill patients, and tests such as serum galactomannan, bronchoalveolar lavage 1-3-β-d-glucan and specific PCR should be interpreted with caution. ICU patients should start adequate antifungal therapy upon suspicion of invasive aspergillosis, without awaiting definitive proof. Voriconazole, and now isavuconazole, are the drugs of choice. Mucormycosis is a rare, but increasingly prevalent disease that occurs mainly in patients with uncontrolled diabetes mellitus, immunocompromised individuals or previously healthy patients with open wounds contaminated with Mucorales. A high proportion of cases are diagnosed in the ICU. Rapidly progressing necrotizing lesions in the rhino-sinusal area, the lungs or skin and soft tissues are the characteristic presentation. Confirmation of diagnosis is based on demonstration of tissue invasion by non-septate hyphae, and by new promising molecular techniques. Control of underlying predisposing conditions, rapid surgical resection and administration of liposomal amphotericin B are the main therapeutic actions, but new agents such as isavuconazole are a promising alternative. Patients with mucormycosis receive a substantial part of their care in ICUs and, despite advances in diagnosis and treatment, mortality remains very high.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; beta-Glucans; Critical Illness; Galactose; Humans; Immunocompromised Host; Intensive Care Units; Invasive Fungal Infections; Lung Diseases, Fungal; Mannans; Mucor; Mucormycosis; Nitriles; Opportunistic Infections; Pyridines; Respiratory System; Triazoles; Voriconazole

Actinomucor elegans is a fungus belonging to mucormycetes and is still probably underdiagnosed due to misidentification. Based on a recent first case of Actinomucor elegans sinusitis in Europe, in an immunocompromised patient under voriconazole treatment, this paper aims to summarize knowledge about A. elegans mucormycoses. Even if the diagnosis of mucormycosis was made using traditional mycology techniques, precise identification of the fungus could only be achieved using molecular tools. In this observation, the galactomannan dosage was positive until the introduction of treatment and surgical debridement. The patient experienced no relapse after one year. By reviewing the four previous A. elegans reported cases and describing the mycological characteristics of this species, we highlight the need to use a combination of tools to improve the diagnostic strategy in such rare and life-threatening clinical situations.

Topics: Adult; Antifungal Agents; Debridement; Europe; Galactose; Humans; Immunocompromised Host; Male; Mannans; Mucorales; Mucormycosis

Outcomes of childhood hematolymphoid malignancies have improved several fold because of immunosuppressive chemotherapy and broad-spectrum antibiotics for managing febrile neutropenia. An apparent trade-off has been an increase in invasive fungal disease (IFD), affecting multiple organs. We report the diagnostic and therapeutic challenges in 8 children with lymphoid cancers who developed intracranial (IC) fungal abscesses between 2010 and 2017.. Children below 15 years of age undergoing treatment for leukemia/lymphoma with clinicoradiologic and microbiologic evidence of IC fungal abscess were included. Demographic details, clinical profile, and management were retrospectively audited. Treatment was guided by European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions for IFD with therapeutic drug monitoring (TDM)-directed azole dosing, and surgical intervention.. Eight patients (4 B-cell acute lymphoblastic leukemia, 2 relapsed B-cell acute lymphoblastic leukemia, and 2 non-Hodgkin lymphoma) were eligible for analysis. Proven, probable, and possible IFDs were seen in 2 (25%), 4 (50%), and 2 (25%) patients, respectively. Proven IFDs were invasive mucormycosis with remaining having mold infections. Cerebrospinal fluid galactomannan was positive in all 4 patients in whom it was tested. TDM was possible in 5/8 (63%) patients. Antifungal therapy was given for a median period of 4.2 months with 5 (63%) patients having complete resolution. Three (37%) patients expired, of which 2 were attributable to IFDs.. IC fungal abscesses in children can cause significant morbidity and mortality in children with hematolymphoid cancers. Evaluation of cerebrospinal fluid galactomannan may help in early diagnosis and therapy. Prolonged antifungal therapy steered by TDM can help achieve resolution in some cases.

Topics: Adolescent; Antifungal Agents; Central Nervous System Fungal Infections; Child; Child, Preschool; Female; Galactose; Humans; Lymphoma, Non-Hodgkin; Male; Mannans; Mucormycosis; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies

To investigate the accuracy of immunohistochemistry (IHC) tests for distinguishing between mucormycosis and aspergillosis and compare the clinical characteristics of mucormycosis patients according to galactomannan (GM) results.. We evaluated diagnostic performance of IHC test with tissue sections of patients with culture-proven invasive fungal infection. In addition, we conducted PCR assay with tissue sections of mucormycosis patients with positive GM results to evaluate the possibility of co-infection.. In culture-proven mucormycosis (n = 13) and aspergillosis (n = 20), the sensitivity and specificity of IHC test were both 100% for mucormycosis and 85% and 100%, respectively, for aspergillosis. Among the 53 patients who met the modified criteria for proven mucormycosis and had GM assay results, 24 (45%) were positive. Compared with those with negative GM results (n = 29), mucormycosis patients with positive GM results had significantly higher incidence of gastrointestinal tract infections (6/24 [25%] vs 0/29 [0%], P = .006) and were more likely to be histomorphologically diagnosed as aspergillosis (7/24 [29%] vs 2/29 [7%], P = .06). PCR assay amplified both Aspergillus- and Mucorales-specific DNA in 6 of these 24 cases.. Immunohistochemistry tests seem useful for compensating for the limitations of histomorphologic diagnosis in distinguishing between mucormycosis and aspergillosis. Some proven mucormycosis patients with positive GM results had histopathology consistent with aspergillosis and gastrointestinal mucormycosis. In addition, about one quarter of these patients revealed the evidence of co-infection with aspergillosis by PCR assay.

Topics: Adult; Aged; Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; DNA, Fungal; Female; Galactose; Humans; Immunohistochemistry; Invasive Fungal Infections; Male; Mannans; Middle Aged; Mucorales; Mucormycosis; Reagent Kits, Diagnostic; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity

Topics: Adult; Aged; Aged, 80 and over; Antigens, Fungal; Aspergillosis; Candidiasis; Disaccharides; Europe; Female; Galactose; Humans; Intersectoral Collaboration; Invasive Fungal Infections; Male; Mannans; Mass Spectrometry; Middle Aged; Mucormycosis; Sensitivity and Specificity; Young Adult

Data on whether positive non-sterile fungal culture has the same clinical value as a positive galactomannan (GM) result are limited.. Patients with biopsy-proven invasive aspergillosis or mucormycosis (over an 8-year period) in whom the results of GM and fungal culture of sputum and/or sinus aspirates were available were enrolled. Biopsy-proven cases were defined if fungal culture from a sterile biopsy specimen gave a positive result and/or hyphae were demonstrated by immunohistochemical staining for aspergillosis and mucormycosis.. A total of 71 patients comprising 30 biopsy-proven cases of aspergillosis including 13 cases with positive sterile cultures and 41 biopsy-proven cases of mucormycosis including eight cases with positive sterile cultures were enrolled. Of 30 patients with aspergillosis, 15 (50%) revealed Aspergillus spp. growth from non-sterile site and none exhibited the agents of mucormycosis growth from non-sterile site. However, of 41 patients with mucormycosis, eight (20%) revealed the agents of mucormycosis growth from non-sterile site and three (7%) exhibited Aspergillus spp. growth from non-sterile site. In terms of GM assays, 23 (77%) of 30 patients with aspergillosis revealed positive GM results, and 17 (41%) of 41 patients with mucormycosis revealed positive GM assays. So, positive fungal culture from non-sterile site (88% [23/26]) were better correlated with the diagnosis than positive GM assay (57% [23/40]) (p value = .01).. Positive fungal cultures from non-sterile sites better correlate with the diagnosis of aspergillosis and mucormycosis based on sterile culture results and histopathological findings than positive GM results.

Topics: Adult; Aged; Aged, 80 and over; Aspergillosis; Aspergillus; Bronchoalveolar Lavage Fluid; Female; Galactose; Humans; Immunohistochemistry; Male; Mannans; Microbiological Techniques; Middle Aged; Mucorales; Mucormycosis; Paraffin Embedding; Republic of Korea; Sputum; Sterilization; Tertiary Care Centers; Young Adult

Acute invasive fungal rhinosinusitis (AIFR) is an aggressive opportunistic infection with a high mortality rate. Recently, non-invasive techniques have been introduced for diagnosis of invasive fungal disease. The purpose of this study is to evaluate the diagnostic significance of serum galactomannan measurement in patients with AIFR.. We conducted a retrospective case-control study of 28 patients with AIFR and 36 fungus ball (FB) patients. We evaluated clinical, laboratory, and pathologic findings along with disease course.. In 28 patients with AIFR, there were 21 cases of invasive aspergillosis (IA) and 7 cases of invasive mucormycosis (IM). The control group was comprised of 36 patients with FB. The three-group analysis showed a statistically significant difference among the groups. At the cut-off value of 0.48, the sensitivity and specificity were 71.4% and 93.0%, respectively. Comparison of mean serum galactomannan levels in 5 non-survivors and 9 survivors at initial measurement showed no significant difference, but that became significantly different 1 week later. Statistical analysis showed that the levels of serum galactomannan decreased significantly according to the measurement-point in within survivor-group analysis. The difference in between survivor-groups analysis was also significant.. Serum galactomannan measurement seems useful for early diagnosis and discrimination of fungal species in patients with AIFR. In addition, clinical outcomes may be related to the levels and patterns of serum galactomannan, especially in IA. The appropriate measurement of galactomannan might be helpful in treating the patients at high risk for AIFR.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aspergillosis; Case-Control Studies; Child; Female; Galactose; Humans; Invasive Fungal Infections; Male; Mannans; Middle Aged; Mucormycosis; Retrospective Studies; Rhinitis; Sensitivity and Specificity; Sinusitis; Young Adult

Compared with major invasive mycoses such as aspergillosis and candidiasis, the antifungal stewardship management strategies of other fungal diseases have different opportunities and considerations. Cryptococcosis, fusariosis and mucormycosis are globally prevalent invasive fungal diseases (IFDs), but are not currently included in antifungal prophylaxis guidelines for immunocompromised hosts. Since the implementation of biomarkers as part of diagnostic screening strategies, the concept of pre-emptive antifungal therapy has emerged for these IFDs. Management of cryptococcosis, the most common IFD worldwide, generally utilizes a pre-emptive or therapeutic strategy that does not involve prophylaxis or empirical antifungal treatment strategies. Antifungal stewardship outcomes for cryptococcosis may vary according to the availability of local resources. Invasive fusariosis, the second-most common form of non-Aspergillus mould infection among haematological malignancy patients, can be managed with pre-emptive (or diagnostic-driven) approaches based on the monitoring of serum galactomannan (GM) antigen in increased-risk populations. The success of antimicrobial stewardship programmes in decreasing the burden of invasive fusariosis in selected patient populations depends on the development and implementation of rapid diagnostic strategies for early and appropriate administration of therapy. Mucormycosis may emerge as a breakthrough IFD in haematology or solid organ transplant recipients receiving antifungals that lack activity against Mucorales. The concept of pre-emptive antifungal therapy has thus arisen for mucormycosis in the haematology setting because of the recent availability of circulating Mucorales DNA measurement. These examples demonstrate the challenges of implementing antifungal stewardship programmes in areas with limited resources, as well as in IFDs that are difficult to diagnose and treat.

Topics: Antifungal Agents; Biomarkers; Cryptococcosis; Fusariosis; Galactose; Humans; Immunocompromised Host; Invasive Fungal Infections; Mannans; Mucormycosis

To investigate the utility of beta-D-glucan (BDG) testing in bronchoalveolar lavage (BAL) fluid for the diagnosis of invasive fungal infection (IFI), as compared to BAL galactomannan (GM).. We retrospectively reviewed medical records of 132 consecutive patients at the National Institutes of Health (NIH) in whom BAL BDG testing was performed for diagnosis of pneumonia. Using the European Organization for Research and Treatment of Cancer/Mycoses Study Group guidelines, we determined which patients had proven or probable IFI, and assessed the diagnostic performance of BAL BDG testing, relative to BAL GM. We also determined the reproducibility of the BDG assay in BAL via repeat testing of patient samples.. Ten patients had Pneumocystis pneumonia, and 34 patients had proven/probable IFI, including 14 with invasive aspergillosis (IA). BAL BDG was 100% sensitive for Pneumocystis. Although BAL BDG had similar sensitivity to BAL GM for the diagnosis of IA and IFI, it exhibited inferior specificity. Repeat testing demonstrated poor reproducibility of the BDG assay in BAL but not in serum.. BDG testing exhibits poor specificity and reproducibility in BAL. Identification of the BAL-specific factors that may interfere with the performance of the assay could improve the clinical usefulness of BAL BDG testing.

Topics: beta-Glucans; Bronchoalveolar Lavage Fluid; Female; Fusariosis; Galactose; Humans; Invasive Pulmonary Aspergillosis; Lung Diseases, Fungal; Male; Mannans; Mucormycosis; Paecilomyces; Pneumonia, Pneumocystis; Reproducibility of Results; Retrospective Studies; Scopulariopsis; Sensitivity and Specificity

Invasive fungal infections remain major causes of infection-related mortality in hematopoietic stem cell transplantation (HSCT) patients. Mixed infections and multiple organ involvement have been reported in these patients. Here, we report a case of mixed Aspergillus and Mucorales infection involving the lungs, brain, spleen and bone in a HSCT patient with relapsed acute myeloid leukemia, who finally improved with triple antifungal therapy and neurosurgical evacuation of brain abscesses. She was put on lifelong secondary prophylaxis with posaconazole with excellent compliance and no sign of toxicity despite over 10 years of drug administration. Serial galactomannan measurements and positron emission tomography/computed tomography were used and were helpful for disease activity monitoring. This is an instructive case of long-term survival after a severe combined mould infection.

Topics: Antifungal Agents; Aspergillosis; Aspergillus; Bone Marrow; Brain; Chemoprevention; Coinfection; Drug Monitoring; Female; Galactose; Humans; Lung; Mannans; Mucorales; Mucormycosis; Spleen; Survivors; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

To describe and estimate the rate of breakthrough invasive mould diseases (IMD) in patients receiving caspofungin.. Retrospective, non-interventional study conducted in three University Hospitals.. Nineteen breakthrough infections have been identified including 13 aspergillosis, 2 mucormycosis, a fusariosis, a Hormographiella aspergillata infection and 2 possible IMD. Cases were equally distributed between the centres. Fourteen patients had a haematologic malignancy, four were transplant recipients (allogeneic haematopoietic stem cells in three, liver in one) and one had hepatic cirrhosis. Caspofungin has been prescribed as prophylaxis (n = 3), empirical therapy (n = 9) or directed therapy for candidemia (n = 5) or aspergillosis (n = 2). Aspergillus galactomannan was positive in serum or in bronchoalveolar lavage fluid in 10 of the 13 aspergillosis. Median duration of caspofungin treatment before breakthrough IMD was 15 days. Nine patients died within twelve weeks. Rate of breakthrough IMD in onco-haematology patients has been estimated to 7.3% for all mould infections and to 4.2% when restricted to documented aspergillosis.. Our data call for Aspergillus galactomannan monitoring and close clinical and radiological examination in case of persistence or recurrence of infection signs in high-risk patients receiving caspofungin.

Topics: Adult; Aged; Antifungal Agents; Caspofungin; Drug Resistance, Fungal; Echinocandins; Female; France; Fusariosis; Galactose; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hospitals, University; Humans; Lipopeptides; Male; Mannans; Middle Aged; Mucormycosis; Pulmonary Aspergillosis

Topics: Antigens, Fungal; Aspergillus; Bronchoalveolar Lavage Fluid; Child; False Positive Reactions; Female; Galactose; Humans; Immunoassay; Lung Diseases, Fungal; Mannans; Mucorales; Mucormycosis; Mycology; Sensitivity and Specificity