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The Lancet. Infectious Diseases Aug 2021With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are... (Review)
Review
Global guideline for the diagnosis and management of rare mould infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.
With increasing numbers of patients needing intensive care or who are immunosuppressed, infections caused by moulds other than Aspergillus spp or Mucorales are increasing. Although antifungal prophylaxis has shown effectiveness in preventing many invasive fungal infections, selective pressure has caused an increase of breakthrough infections caused by Fusarium, Lomentospora, and Scedosporium species, as well as by dematiaceous moulds, Rasamsonia, Schizophyllum, Scopulariopsis, Paecilomyces, Penicillium, Talaromyces and Purpureocillium species. Guidance on the complex multidisciplinary management of infections caused by these pathogens has the potential to improve prognosis. Management routes depend on the availability of diagnostic and therapeutic options. The present recommendations are part of the One World-One Guideline initiative to incorporate regional differences in the epidemiology and management of rare mould infections. Experts from 24 countries contributed their knowledge and analysed published evidence on the diagnosis and treatment of rare mould infections. This consensus document intends to provide practical guidance in clinical decision making by engaging physicians and scientists involved in various aspects of clinical management. Moreover, we identify areas of uncertainty and constraints in optimising this management.
Topics: Animals; Disease Management; Fungi; Humans; Mycology; Mycoses; Practice Guidelines as Topic; Societies, Medical
PubMed: 33606997
DOI: 10.1016/S1473-3099(20)30784-2 -
Journal of Fungi (Basel, Switzerland) Oct 2020Fosmanogepix is a first-in-class antifungal currently in Phase 2 clinical trials for the treatment of invasive fungal infections caused by and rare molds. Fosmanogepix... (Review)
Review
Fosmanogepix is a first-in-class antifungal currently in Phase 2 clinical trials for the treatment of invasive fungal infections caused by and rare molds. Fosmanogepix is the N-phosphonooxymethylene prodrug of manogepix, an inhibitor of the fungal enzyme Gwt1. Manogepix demonstrates broad spectrum in vitro activity against yeasts and molds, including difficult to treat pathogens. Because of its novel mechanism of action, manogepix retains potency against many resistant strains including echinocandin-resistant and azole-resistant Manogepix is also active against pathogens that demonstrate intrinsic resistance to other drug classes, such as , and with variable activity against Mucorales. Fosmanogepix demonstrates significant in vivo efficacy in mouse and rabbit disseminated infection models due to and as well as pulmonary infection models of and Clinical trials demonstrated high oral bioavailability (>90%), enabling switching between fosmanogepix intravenous and oral formulations without compromising blood levels. Favorable drug-drug interaction, tolerability, and wide tissue distribution profiles are observed making fosmanogepix an attractive option for the treatment of invasive fungal infections. This systematic review summarizes the findings of published data on fosmanogepix.
PubMed: 33105672
DOI: 10.3390/jof6040239 -
Journal of Fungi (Basel, Switzerland) Jul 2019The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses.... (Review)
Review
The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans spp., including , a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus species, Mucorales, and spp The agricultural application of triazole pesticides has driven an emergence of azole-resistant in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including , which cause disseminated mycoses globally, primarily in HIV infected patients, and and , causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by has emerged as an important disease of felines and people.
PubMed: 31330862
DOI: 10.3390/jof5030067 -
Paediatric Respiratory Reviews Mar 2021Fungal lung disease in the paediatric population occurs with distinct features in the immunocompetent, in immunocompromised patients and in people with cystic fibrosis.... (Review)
Review
Fungal lung disease in the paediatric population occurs with distinct features in the immunocompetent, in immunocompromised patients and in people with cystic fibrosis. Pulmonary mycoses are the least prevalent in immunocompetent children, with the most common diseases being the endemic mycoses and Aspergillomas. Filamentous fungi such as Aspergillus and Scedosporium have been isolated with increased frequency in recent years from the respiratory secretions of individuals with cystic fibrosis. Undoubtedly, fungal respiratory infections are encountered with increased frequency and severity in patients with impaired immune systems, such as patients with malignancies, solid organ or bone marrow transplants and immunodeficiencies [1].
Topics: Child; Cystic Fibrosis; Fungi; Humans; Lung Diseases, Fungal; Mycoses; Scedosporium
PubMed: 32527608
DOI: 10.1016/j.prrv.2020.04.009 -
Therapeutic Advances in Infectious... 2024Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell... (Review)
Review
Invasive fungal infections are increasingly encountered with the expansion of iatrogenic immunosuppression, including not only solid organ and hematopoietic stem cell transplant recipients but also patients with malignancies or autoimmune diseases receiving immunomodulatory therapies, such as Bruton Tyrosine Kinase (BTK) inhibitor. Their attributable mortality remains elevated, part of which is a contribution from globally emerging resistance in both molds and yeasts. Because antifungal susceptibility test results are often unavailable or delayed, empiric and tailored antifungal approaches including choice of agent(s) and use of combination therapy are heterogeneous and often based on clinician experience with knowledge of host's net state of immunosuppression, prior antifungal exposure, antifungal side effects and interaction profile, clinical severity of disease including site(s) of infection and local resistance data. In this review, we aim to summarize previous recommendations and most recent literature on treatment of invasive mold and yeast infections in adults to guide optimal evidence-based therapeutic approaches. We review the recent data that support use of available antifungal agents, including the different triazoles that have now been studied in comparison to previously preferred agents. We discuss management of complex infections with specific emerging fungi such as spp., spp., , and . We briefly explore newer antifungal agents or formulations that are now being investigated to overcome therapeutic pitfalls, including but not limited to olorofim, rezafungin, fosmanogepix, and encochleated Amphotericin B. We discuss the role of surgical resection or debridement, duration of treatment, follow-up modalities, and need for secondary prophylaxis, all of which remain challenging, especially in patients chronically immunocompromised or awaiting more immunosuppressive therapies.
PubMed: 38249542
DOI: 10.1177/20499361231224980 -
Internal Medicine Journal Nov 2021Invasive fungal disease (IFD) due to moulds other than Aspergillus is a significant cause of mortality in patients with malignancies or post haemopoietic stem cell...
Invasive fungal disease (IFD) due to moulds other than Aspergillus is a significant cause of mortality in patients with malignancies or post haemopoietic stem cell transplantation. The current guidelines focus on the diagnosis and management of the common non-Aspergillus moulds (NAM), such as Mucorales, Scedosporium species (spp.), Lomentospora prolificans and Fusarium spp. Rare but emerging NAM including Paecilomyces variotii, Purpureocillium lilacinum and Scopulariopsis spp. are also reviewed. Culture and histological examination of tissue biopsy specimens remain the mainstay of diagnosis, but molecular methods are increasingly being used. As NAM frequently disseminate, blood cultures and skin examination with biopsy of any suspicious lesions are critically important. Treatment requires a multidisciplinary approach with surgical debridement as a central component. Other management strategies include control of the underlying disease/predisposing factors, augmentation of the host response and the reduction of immunosuppression. Carefully selected antifungal therapy, guided by susceptibility testing, is critical to cure. We also outline novel antifungal agents still in clinical trial which offer substantial potential for improved outcomes in the future. Paediatric recommendations follow those of adults. Ongoing epidemiological research, improvement in diagnostics and the development of new antifungal agents will continue to improve the poor outcomes that have been traditionally associated with IFD due to NAM.
Topics: Adult; Antifungal Agents; Aspergillus; Child; Fungi; Hematology; Humans; Invasive Fungal Infections
PubMed: 34937139
DOI: 10.1111/imj.15592 -
Current Opinion in Organ Transplantation Jun 2022Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction.... (Review)
Review
PURPOSE OF REVIEW
Infections with multiresistant organisms are an emerging problem, cause early mortality post lung transplantation and are sometimes associated with graft dysfunction. Frequently they raise questions about the selection of lung transplant candidates and therapeutic management post lung transplantation. There are no guidelines and management must be individualized. This review summarizes the available therapeutic options in cases of multidrug-resistant (MDR) organisms and outcomes after lung transplant.
RECENT FINDINGS
Improvements in diagnosis, new and more effective drugs and the experience gained in the management of these infections in lung transplantation, lead to a more optimistic horizon than that found a decade ago.
SUMMARY
Update on the management of Burkholderia cepacia complex, Mycobacterium abscessus complex, Aspergillus spp., Scedosporium spp. and Lomentospora prolificans infections. This review clarifies current posttransplant outcomes and adds a little hope in these scenarios.
Topics: Bacteria; Humans; Invasive Fungal Infections; Lung Transplantation; Scedosporium
PubMed: 35283468
DOI: 10.1097/MOT.0000000000000976 -
Open Forum Infectious Diseases Feb 2023Management of infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including...
BACKGROUND
Management of infections remains challenging. We described predisposing factors, clinical manifestations, and outcomes of these rare mold infections, including predictors of early (1-month) and late (18-month) all-cause mortality and treatment failure.
METHODS
We conducted a retrospective Australian-based observational study of proven/probable infections from 2005 to 2021. Data on patient comorbidities, predisposing factors, clinical manifestations, treatment, and outcomes up to 18 months were collected. Treatment responses and death causality were adjudicated. Subgroup analyses, multivariable Cox regression, and logistic regression were performed.
RESULTS
Of 61 infection episodes, 37 (60.7%) were attributable to . Forty-five of 61 (73.8%) were proven invasive fungal diseases (IFDs), and 29 of 61 (47.5%) were disseminated. Prolonged neutropenia and receipt of immunosuppressant agents were documented in 27 of 61 (44.3%) and 49 of 61 (80.3%) episodes, respectively. Voriconazole/terbinafine was administered in 30 of 31 (96.8%) infections, and voriconazole alone was prescribed for 15 of 24 (62.5%) spp infections. Adjunctive surgery was performed in 27 of 61 (44.3%) episodes. Median time to death post-IFD diagnosis was 9.0 days, and only 22 of 61 (36.1%) attained treatment success at 18 months. Those who survived beyond 28 days of antifungal therapy were less immunosuppressed with fewer disseminated infections (both < .001). Disseminated infection and hematopoietic stem cell transplant were associated with increased early and late mortality rates. Adjunctive surgery was associated with lower early and late mortality rates by 84.0% and 72.0%, respectively, and decreased odds of 1-month treatment failure by 87.0%.
CONCLUSIONS
Outcomes associated with infections is poor, particularly with infections or in the highly immunosuppressed population.
PubMed: 36861090
DOI: 10.1093/ofid/ofad059 -
Trends in Microbiology Dec 2019
Topics: Antifungal Agents; Cystic Fibrosis; Humans; Immunocompromised Host; Invasive Fungal Infections; Scedosporium; Soil Microbiology
PubMed: 31378439
DOI: 10.1016/j.tim.2019.07.003 -
Internal Medicine Journal Aug 2023Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with...
Scedosporium and Lomentospora species are environmental moulds that are virulent in immunocompromised hosts and rarely cause bloodstream infection (BSI). Patients with Scedosporium and Lomentospora species BSI were identified by the state public laboratory service in Queensland, Australia, over a 20-year period. Twenty-two incident episodes occurred among 21 residents; one patient had a second episode 321 days following the first. Of these, 18 were Lomentospora prolificans, three were Scedosporium apiospermum complex and one was a nonspeciated Scedosporium species. Seventeen (81%) patients died during their index admission, and all-cause mortality at 30, 90 and 365 days was 73%, 82% and 91% respectively. All 20 patients with haematological malignancy died within 365 days of follow-up with a median time to death of 9 days (interquartile range, 6-20 days) following diagnoses of BSI.
Topics: Adult; Female; Humans; Male; Middle Aged; Australia; Fungemia; Immunocompromised Host; Leukemia; Scedosporium
PubMed: 37599232
DOI: 10.1111/imj.16198