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Mycoses Sep 2019Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining... (Review)
Review
Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology.
Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.
Topics: Antifungal Agents; Aspergillosis; Clinical Trials as Topic; Europe; Humans; Invasive Fungal Infections; Mucormycosis; Mycoses; Risk Factors; Treatment Failure
PubMed: 31254420
DOI: 10.1111/myc.12960 -
Infectious Disease Clinics of North... Jun 2021Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and... (Review)
Review
Various uncommon fungal pathogens have been increasingly identified as causes of disseminated and invasive fungal disease (IFD) worldwide. Growing recognition and clinical knowledge of these emerging fungal pathogens has occurred through improved molecular diagnostics, nucleic sequence databases, and taxonomic reclassification of medically significant fungi. However, emerging fungal diseases carry significant morbidity and mortality and, due to a paucity of published literature, the collective clinical experience with these fungi is often limited. In this review, we focus on unusual emerging fungal pathogens not extensively covered elsewhere in this issue of Infectious Diseases Clinics of North America.
Topics: Communicable Diseases, Emerging; Fungi; Humans; Invasive Fungal Infections; Mycoses; North America; Opportunistic Infections
PubMed: 34016278
DOI: 10.1016/j.idc.2021.03.014 -
Trends in Parasitology Oct 2021
Topics: Batrachochytrium; Classification; Mycoses
PubMed: 34023213
DOI: 10.1016/j.pt.2021.04.014 -
Clinical Transplantation Sep 2019These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of...
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention and management of blastomycosis, histoplasmosis, and coccidioidomycosis in the pre- and post-transplant period. Though each of these endemic fungal infections has unique epidemiology and clinical manifestations, they all share a predilection for primary pulmonary infection and may cause disseminated infection, particularly in immunocompromised hosts. Culture remains the gold standard for definitive diagnosis, but more rapid diagnosis may be achieved with direct visualization of organisms from clinical specimens and antigen-based enzyme immunoassay assays. Serology is of limited utility in transplant recipients. The mainstay of treatment for severe infections remains liposomal amphotericin followed by a step-down azole therapy. Cases of mild to moderate severity with no CNS involvement may be treated with azole therapy alone. The newer generation azoles provide additional treatment options, but supported currently with limited clinical efficacy data. Azole therapy in transplant recipients presents a unique challenge owing to the drug-drug interactions with immunosuppressant agents. Therapeutic drug monitoring of azole levels is an essential component of effective and safe therapy. Infection prevention centers around minimizing epidemiological exposures, early clinical recognition, and azole prophylaxis in selected individuals.
Topics: Antifungal Agents; Endemic Diseases; Fungi; Humans; Mycoses; Organ Transplantation; Practice Guidelines as Topic; Societies, Medical; Transplant Recipients
PubMed: 30924967
DOI: 10.1111/ctr.13553 -
Annals of the American Thoracic Society Oct 2021
Topics: Antifungal Agents; Humans; Mycoses
PubMed: 33901407
DOI: 10.1513/AnnalsATS.202103-300LE -
Indian Journal of Medical Microbiology 2023Patients with hematologic malignancies (HM) carries a significant risk of developing invasive fungal infection (IFI) and are associated with a high risk of attributable... (Review)
Review
BACKGROUND
Patients with hematologic malignancies (HM) carries a significant risk of developing invasive fungal infection (IFI) and are associated with a high risk of attributable morbidity and mortality.
OBJECTIVES
This review has highlighted the importance of diagnosis and management of invasive fungal infections in highly immunocompromised Hemato-Oncology patients.
CONTENT
IFI continues to be a therapeutic issue in immunocompromised HM patients despite of many advancements in the field of fungal diagnosis and therapies. Non-specific and often overlapping signs and symptoms render fungal infections clinically undifferentiated from bacterial infections. Definite diagnosis requires microbiological diagnostic procedures in addition to imaging techniques. Many international committees have formulated definitions to aid in the diagnosis of IFI in immunocompromised patients and assigned 3 levels of probability to the diagnosis "proven," "probable," and "possible" IFI. Early specific risk-based antifungal strategies such as prophylaxis, pre-emptive and empirical therapies, are common practices in HM patients. For low-risk patients, fluconazole is recommended as primary prophylaxis, while, posaconazole and voriconazole are recommended for high-risk patients. Emerging antifungal-resistant IFIs and breakthrough fungal infections are the new threat to these heavily immunosuppressed patients. Antifungal agents such as azoles have variable pharmacokinetics leading to uncertainty in the drug dose-exposure relationship, especially in the initiation phase. TDM (therapeutic drug monitoring) of voriconazole is strongly recommended.
Topics: Humans; Antifungal Agents; Voriconazole; Invasive Fungal Infections; Mycoses; Neoplasms
PubMed: 37356843
DOI: 10.1016/j.ijmmb.2023.01.011 -
Annals of Internal Medicine Dec 2022
Topics: Humans; Mycoses; Endemic Diseases
PubMed: 36410005
DOI: 10.7326/M22-2371 -
Current Opinion in Microbiology Aug 2021The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and... (Review)
Review
The allergic airway diseases chronic rhinosinusitis (CRS), allergic fungal rhinosinusitis (AFRS), asthma, allergic bronchopulmonary mycosis/aspergillosis (ABPM/A), and cystic fibrosis (CF) share a common immunological signature marked by T2 and T17 cell predominant immune responses, the production of IgE antibody, and a typical inflammatory cell infiltrate that includes eosinophils and other innate immune effector cells. Severe forms of these disorders have long been recognized as being related to hypersensitivity reactions to environmental fungi. Increasingly however,environmental fungi are assuming a more primary role in the etiology of these disorders, with airway mycosis, a type of non-invasive airway fungal infection, recognized as an essential driving factor in at least severe subsets of allergic airway diseases. In this review, we consider recent progress made in understanding the immune mechanisms that drive airway mycosis-related diseases, improvements in immune-based diagnostic strategies, and therapeutic approaches that target key immune pathways.
Topics: Aspergillosis, Allergic Bronchopulmonary; Humans; Immunity; Mycoses; Respiratory System; Sinusitis
PubMed: 34052540
DOI: 10.1016/j.mib.2021.04.009 -
APMIS : Acta Pathologica,... Jul 2022Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for... (Review)
Review
Animal models of invasive fungal infections have been developed and are applied in a huge number of different animal species for a number of research purposes, for example, the study of pathogenesis, defense mechanisms, and therapeutic strategies. From the different models, which in most cases are based on the same fungal species and often the same strain, as in spontaneous human infections, fundamental results and knowledge of the diagnosis, progression, prophylaxis, and therapy have been achieved. However, in all models, one should be critical with respect to mimicking the disease entity of humans, which is often the focus of the research. In many of the models for instance, the time course is different to the one of humans, and in others, the propensity for localization and containment in specific organs does not parallel the situation in humans. Nevertheless, many animal models of invasive mycoses have proven valuable in a number of research areas. With regard to new generations of anti-mycotic drugs, the models play an essential role in demonstrating antifungal activity, as well as in demonstrating the absence of toxic side effects, a critical step which cannot be accomplished by in vitro studies.
Topics: Animals; Antifungal Agents; Invasive Fungal Infections; Models, Animal; Mycoses
PubMed: 33644890
DOI: 10.1111/apm.13110 -
Clinics in Laboratory Medicine Dec 2020Recent improvements in next-generation sequencing technologies have enabled clinical laboratories to increasingly pursue pathogen genomics for infectious disease... (Review)
Review
Recent improvements in next-generation sequencing technologies have enabled clinical laboratories to increasingly pursue pathogen genomics for infectious disease diagnosis. Clinical laboratories can also benefit from whole-genome sequence characterization of cultured isolates, helping to resolve infection prevention questions pertaining to pathogen outbreaks and surveillance. Metagenomic sequencing from primary specimens can also provide laboratories with an unbiased universal test for situations where traditional methods fail to identify infectious etiologies despite, high clinical suspicion. Here, the most useful applications of whole-genome sequence and metagenomic sequencing are summarized, as are the main advantages, limitations, and considerations for building an in-house clinical genomics program.
Topics: Bacterial Infections; Genomics; High-Throughput Nucleotide Sequencing; Humans; Metagenomics; Microbiological Techniques; Molecular Diagnostic Techniques; Mycoses; Whole Genome Sequencing
PubMed: 33121614
DOI: 10.1016/j.cll.2020.08.003