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Infection Aug 2018Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal infections of the central nervous system (FIs-CNS) have become significantly more common over the past 2 decades. Invasion of the CNS largely depends on the immune status of the host and the virulence of the fungal strain. Infections with fungi cause a significant morbidity in immunocompromised hosts, and the involvement of the CNS may lead to fatal consequences.
METHODS
One hundred and thirty-five articles on fungal neuroinfection in PubMed, Google Scholar, and Cochrane databases were selected for review using the following search words: "fungi and CNS mycoses", CNS fungal infections", "fungal brain infections", " fungal cerebritis", fungal meningitis", "diagnostics of fungal infections", and "treatment of CNS fungal infections". All were published in English with the majority in the period 2000-2018. This review focuses on the current knowledge of the epidemiology, clinical presentations, diagnosis, and treatment of selected FIs-CNS.
RESULTS
The FIs-CNS can have various clinical presentations, mainly meningitis, encephalitis, hydrocephalus, cerebral abscesses, and stroke syndromes. The etiologic factors of neuroinfections are yeasts (Cryptococcus neoformans, Candida spp., Trichosporon spp.), moniliaceous moulds (Aspergillus spp., Fusarium spp.), Mucoromycetes (Mucor spp., Rhizopus spp.), dimorphic fungi (Blastomyces dermatitidis, Coccidioides spp., Histoplasma capsulatum), and dematiaceous fungi (Cladophialophora bantiana, Exophiala dermatitidis). Their common route of transmission is inhalation or inoculation from trauma or surgery, with subsequent hematogenous or contiguous spread. As the manifestations of FIs-CNS are often non-specific, their diagnosis is very difficult. A fast identification of the etiological factor of neuroinfection and the application of appropriate therapy are crucial in preventing an often fatal outcome. The choice of effective drug depends on its extent of CNS penetration and spectrum of activity. Pharmaceutical formulations of amphotericin B (AmB) (among others, deoxycholate-AmBd and liposomal L-AmB) have relatively limited distribution in the cerebrospinal fluid (CSF); however, their detectable therapeutic concentrations in the CNS makes them recommended drugs for the treatment of cryptococcal meningoencephalitis (AmBd with flucytosine) and CNS candidiasis (L-AmB) and mucormycosis (L-AmB). Voriconazole, a moderately lipophilic molecule with good CNS penetration, is recommended in the first-line therapy of CNS aspergillosis. Other triazoles, such as posaconazole and itraconazole, with negligible concentrations in the CSF are not considered effective drugs for therapy of CNS fungal neuroinfections. In contrast, clinical data have shown that a novel triazole, isavuconazole, achieved considerable efficacy for the treatment of some fungal neuroinfections. Echinocandins with relatively low or undetectable concentrations in the CSF do not play meaningful role in the treatment of FIs-CNS.
CONCLUSION
Although the number of fungal species causing CNS mycosis is increasing, only some possess well-defined treatment standards (e.g., cryptococcal meningitis and CNS aspergillosis). The early diagnosis of fungal infection, accompanied by identification of the etiological factor, is needed to allow the selection of effective therapy in patients with FIs-CNS and limit their high mortality.
Topics: Blood-Brain Barrier; Central Nervous System Fungal Infections; Disease Management; Fungi; Host-Pathogen Interactions; Humans; Risk Factors; Virulence
PubMed: 29785613
DOI: 10.1007/s15010-018-1152-2 -
Expert Review of Respiratory Medicine Jul 2020Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised... (Review)
Review
INTRODUCTION
Fungal infections are increasingly encountered in clinical practice due to more favorable environmental conditions and increasing prevalence of immunocompromised individuals. The diagnostic approach for many fungal pathogens continues to evolve. Herein, we outline available diagnostic tests for the most common fungal infections with a focus on recent advances and future directions.
AREAS COVERED
We discuss the diagnostic testing methods for angioinvasive molds ( spp. and spp.), invasive yeast ( spp. and ssp.), Pneumocystis, and endemic fungi ( sp., Coccidioides sp., and Hitoplasma sp.). The PubMed-NCBI database was searched within the past 5 years to identify the most recent available literature with dates extended in cases where literature was sparse. Diagnostic guidelines were utilized when available with references reviewed.
EXPERT OPINION
Historically, culture and/or direct visualization of fungal organisms were required for diagnosis of infection. Significant limitations included ability to collect specimens and delayed diagnosis associated with waiting for culture results. Antigen and antibody testing have made great strides in allowing quicker diagnosis of fungal infections but can be limited by low sensitivity/specificity, cross-reactivity with other fungi, and test availability. Molecular methods have a rich history in some fungal diseases, while others continue to be developed.
Topics: Aspergillus; Blastomyces; Candida; Coccidioides; Cryptococcus; Histoplasma; Humans; Lung Diseases, Fungal; Mucor; Pneumocystis; Pneumonia
PubMed: 32290725
DOI: 10.1080/17476348.2020.1753506 -
The Journal of Antimicrobial... Mar 2017Infections caused by filamentous fungi represent a major burden in the ICU. Invasive aspergillosis is emerging in non-neutropenic individuals with predisposing... (Review)
Review
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; 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; beta-Glucans
PubMed: 28355466
DOI: 10.1093/jac/dkx032 -
Journal of Fungi (Basel, Switzerland) Jul 2022COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino-orbital mucormycosis was... (Review)
Review
COVID-19-associated mucormycosis (CAM) emerged as an epidemic in certain parts of the world amidst the global COVID-19 pandemic. While rhino-orbital mucormycosis was well reported during the pandemic, in the absence of routine diagnostic facilities including lower airway sampling, pulmonary mucormycosis was probably under-recognized. In this review, we have focused on the epidemiology and management of COVID-19-associated pulmonary mucormycosis (CAPM). CAPM is a deadly disease and mortality can be as high as 80% in the absence of early clinical suspicion and treatment. While histopathological examination of tissue for angio-invasion and cultures have remained gold standard for diagnosis, there is an increasing interest in molecular and serological methods to facilitate diagnosis in critically ill patients and often, immune-suppressed hosts who cannot readily undergo invasive sampling. Combined medical and surgical treatment offers more promise than standalone medical therapy. Maintaining adequate glycemic control and prudent use of steroids which can be a double-edged sword in COVID-19 patients are the key preventative measures. We would like to emphasize the urgent need for the development and validation of reliable biomarkers and molecular diagnostics to facilitate early diagnosis.
PubMed: 35887466
DOI: 10.3390/jof8070711 -
Journal of Fungi (Basel, Switzerland) Jun 2020Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven... (Review)
Review
Mucormycosis is an emerging fungal infection caused by Mucorales with an unacceptable high mortality rate. Mucorales is a complex fungal group, including eleven different genera that can infect humans. This heterogeneity is associated with species-specific invasion pathways and responses to the host defense mechanisms. The host innate immune system plays a major role in preventing Mucorales growth and host invasion. In this system, macrophages are the main immune effector cells in controlling these fungi by rapid and efficient phagocytosis of the spores. However, Mucorales have evolved mechanisms to block phagosomal maturation and species-specific mechanisms to either survive as dormant spores inside the macrophage, as species, or geminate and escape, as species. Classical fungal models of mucormycosis, mostly , have made important contributions to elucidate key aspects of the interaction between Mucorales and macrophages, but they lack robust tools for genetic manipulation. The recent introduction of the genetically tractable as a model of mucormycosis offers the possibility to analyze gene function. This has allowed the identification of regulatory pathways that control the fungal response to phagocytosis, including a non-canonical RNAi pathway (NCRIP) that regulates the expression of most genes regulated by phagocytosis.
PubMed: 32604972
DOI: 10.3390/jof6020094 -
Current Fungal Infection Reports May 2023Invasive mucormycosis (IM), caused by fungi of the order Mucorales, is one of the deadliest fungal infection among hematologic cancer patients. Its incidence is also... (Review)
Review
PURPOSE OF REVIEW
Invasive mucormycosis (IM), caused by fungi of the order Mucorales, is one of the deadliest fungal infection among hematologic cancer patients. Its incidence is also increasingly reported in immunocompetent individuals, notably with the COVID-19 pandemic. Therefore, there is an urgent need for novel diagnostic and therapeutic approaches of IM. This review discusses the current advances in this field.
RECENT FINDINGS
Early diagnosis of IM is crucial and can be improved by Mucorales-specific PCR and development of lateral-flow immunoassays for specific antigen detection. The spore coat proteins (CotH) are essential for virulence of the Mucorales and may represent a target for novel antifungal therapies. Adjuvant therapies boosting the immune response, such as interferon-γ, anti-PDR1 or fungal-specific chimeric antigen receptor (CAR) T-cells, are also considered.
SUMMARY
The most promising perspectives for improved management of IM consist of a multilayered approach targeting both the pathogen and the host immune system.
PubMed: 37360854
DOI: 10.1007/s12281-023-00463-3 -
Annals of Burns and Fire Disasters Mar 2015Local or general fungal infection remain a very serious event in burns. Burns have numerous risk factors for such, infections associated with depressed immunity....
Local or general fungal infection remain a very serious event in burns. Burns have numerous risk factors for such, infections associated with depressed immunity. Candida, Aspergillus and mucor fungi prevail in wound infections. The two latest are especially serious and impairing. Diagnosis is based on anatomo-pathological and mycological examination of skin samples. Treatment is mainly surgical. Medical therapy depends on antifungal susceptibility. Most fungemias are candidemias. Diagnosis is difficult and often based on clinical suspicion. Treatment uses echinocandin and fluconazole.
PubMed: 26668558
DOI: No ID Found -
Frontiers in Cellular and Infection... 2023
Topics: Humans; Mucormycosis
PubMed: 37743863
DOI: 10.3389/fcimb.2023.1280784 -
Gastroenterology Research Oct 2023Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum , order , with most cases caused... (Review)
Review
Mucormycosis is a devastating fungal infection that is usually seen in immunocompromised hosts. It is caused by fungi of the subphylum , order , with most cases caused by , , or species. It can involve any organ system and can disseminate in severe cases. Lately, there has been an increased number of reports for mucormycosis infection in immunocompetent patients. Gastrointestinal system involvement is rare compared to other organ systems but has been increasingly reported in the literature. Mucormycosis can affect any part of the gastrointestinal tract and lead to different presentations depending on the area of involvement. Due to the paucity of the condition, there has been no specific guidelines on how to treat gastrointestinal mucormycosis. In this review, we discuss the risk factors of gastrointestinal mucormycosis, clinical presentation, approach to diagnosis, and most recent treatment modalities for gastrointestinal mucormycosis.
PubMed: 37937225
DOI: 10.14740/gr1662 -
World Journal of Radiology Nov 2014Spectrum of acute renal infections includes acute pyelonephritis, renal and perirenal abscesses, pyonephrosis, emphysematous pyelonephritis and emphysematous cystitis.... (Review)
Review
Spectrum of acute renal infections includes acute pyelonephritis, renal and perirenal abscesses, pyonephrosis, emphysematous pyelonephritis and emphysematous cystitis. The chronic renal infections that we routinely encounter encompass chronic pyelonephritis, xanthogranulomatous pyelonephritis, and eosinophilic cystitis. Patients with diabetes, malignancy and leukaemia are frequently immunocompromised and more prone to fungal infections viz. angioinvasive aspergillus, candida and mucor. Tuberculosis and parasitic infestation of the kidney is common in tropical countries. Imaging is not routinely indicated in uncomplicated renal infections as clinical findings and laboratory data are generally sufficient for making a diagnosis. However, imaging plays a crucial role under specific situations like immunocompromised patients, treatment non-responders, equivocal clinical diagnosis, congenital anomaly evaluation, transplant imaging and for evaluating extent of disease. We aim to review in this article the varied imaging spectrum of renal inflammatory lesions.
PubMed: 25431641
DOI: 10.4329/wjr.v6.i11.865