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Current Fungal Infection Reports[JOURNAL]

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Spectrum of Mucormycosis Before and During COVID-19: Epidemiology, Diagnosis, and Current Therapeutic Interventions.

Mansoor S, Ahmed TI, Happa K … +3 more , Sultan M, Manhas S, Shamas S

Curr Fungal Infect Rep · 2022 · PMID 35967987 · Full text

PURPOSE OF REVIEW: More than half a billion people have been infected and 6.2 million killed by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) since the start of the pandemic in 2019. Systemic gluc... PURPOSE OF REVIEW: More than half a billion people have been infected and 6.2 million killed by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) since the start of the pandemic in 2019. Systemic glucocorticoids are a double-edged sword, on the one hand, life-saving in treating COVID-19 complications while on the other hand, potentially leading to life-and-limb-threatening opportunistic fungal infections. Mucormycosis (MM) is caused by the mucormycetes family. Although rare, it is characterized by high mortality and significant morbidity. The gross similarities observed with other fungal infections which respond to different treatment regimens have made it all the more imperative to quickly and sensitively diagnose and treat MM. This review discusses the epidemiology of MM before and during the COVID-19 pandemic, associated risk factors, COVID-19-associated MM, diagnosis, and current therapeutic interventions. RECENT FINDINGS: There has been a widespread and worrisome trend of rising in cases of MM, worldwide, but more so in the Indian subcontinent, where it is nicknamed the "black fungus." This upsurge has picked up the pace ever since the start of the COVID-19 pandemic. Necrosis is secondary to the angio-invasive and pro-thrombotic nature of the mold resulting in extensive lesions presenting mostly as rhino-orbital MM (ROM) and rhino-orbito-cerebral MM (ROCM). Infection is mostly observed in subjects with underlying risk factors such as uncontrolled diabetes, those receiving hematopoietic stem cell transplant, and/or on corticosteroid or immunosuppressive therapy, although it is widely suspected that other factors such as iron and zinc may play a role in the pathogenesis of MM. The "One world one guideline" strategy advocates both prophylactic anti-fungal therapy along with aggressive, prompt, and individualized treatment with anti-fungal drugs such as amphotericin B in addition to vigorous surgical intervention. High-risk groups need particularly rapid diagnosis although empirical anti-fungal therapy may not be delayed. Speeding diagnostic turnaround times are essential to institute early therapy, and there is much scope for newer modalities such as PCR, matrix-assisted laser desorption ionization-time of flight mass spectrometry, and whole-genome sequencing in such endeavors. The results of strict monitoring of blood glucose levels along with rational and limited use of steroids and immunomodulatory drugs have proven to be a significant preventive measure. SUMMARY: The significant rise in cases of MM worldwide has necessitated viewing each case with a strong index of suspicion. Adoption of rapid diagnostics, early antifungal therapy, and prompt surgical interventions are essential, while high-risk groups need particular focused care which may include prophylactic anti-fungal therapy, limited steroid use, and meticulous control of the underlying disease. Developing quicker and more sensitive diagnostic modalities has great potential to improve the detection and management of MM.

Overview of COVID-19-Associated Invasive Fungal Infection.

Shishido AA, Mathew M, Baddley JW

Curr Fungal Infect Rep · 2022 · PMID 35846240 · Full text

PURPOSE OF REVIEW: Invasive fungal infections are a complication of COVID-19 disease. This article reviews literature characterizing invasive fungal infections associated with COVID-19. RECENT FINDINGS: Multiple invasive... PURPOSE OF REVIEW: Invasive fungal infections are a complication of COVID-19 disease. This article reviews literature characterizing invasive fungal infections associated with COVID-19. RECENT FINDINGS: Multiple invasive fungal infections including aspergillosis, candidiasis, pneumocystosis, other non- molds, and endemic fungi have been reported in patients with COVID-19. Risk factors for COVID-19-associated fungal disease include underlying lung disease, diabetes, steroid or immunomodulator use, leukopenia, and malignancy. COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) are the most common fungal infections described. However, there is variability in the reported incidences related to use of differing diagnostic algorithms. SUMMARY: Fungal pathogens are important cause of infection in patients with COVID-19, and the diagnostic strategies continue to evolve. Mortality in these patients is increased, and providers should operate with a high index of suspicion. Further studies will be required to elucidate the associations and pathogenesis of these diseases and best management and prevention strategies.

COVID-19 and Plethora of Fungal Infections.

Kundu R, Singla N

Curr Fungal Infect Rep · 2022 · PMID 35432691 · Full text

PURPOSE OF REVIEW: Severe-acute respiratory coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) has been the single most important pathogen driving health care delivery system for the last one and hal... PURPOSE OF REVIEW: Severe-acute respiratory coronavirus 2 (SARS-CoV-2) causing corona virus disease 2019 (COVID-19) has been the single most important pathogen driving health care delivery system for the last one and half years. Now, as the time is passing, many issues related to co-infections/secondary infections/superinfections in COVID-19 patients are emerging. The literature is getting enriched everyday by addition of reports from all over the world for the same. The purpose of this review is to decipher the plethora of fungal infections in COVID-19. RECENT FINDINGS: COVID-19 infection along with it brought many risk factors namely lung injury, immunosuppression, need for oxygen therapy, monoclonal antibodies, steroid therapy, etc. which are known predisposing factors for fungal infections. Rather the extent and severity of fungal pathogens has been so much that it has led to new terminologies like CAC (COVID-19-associated ), CAPA (COVID-19-associated pulmonary aspergillosis) and CAM (COVID-19-associated mucormycosis). There is increase in invasiveness of , prevalence of aspergillosis in COVID-19 damaged lung and outbreak of mucormycosis in COVID-19 patients resulting in "double trouble," keeping laboratory personnel, clinicians, and intensivists on their toes in managing these patients. SUMMARY: Awareness and understanding regarding these possible complications is necessary to decrease the morbidity and mortality among patients. The COVID-19 and fungal coinfections may bring more insight into ways of pathogenesis of fungal infections, need for better antifungal agents, quick diagnostic modalities, and better management policies in the near future.

Sporotrichosis in Children: Case series and Narrative Review.

Queiroz-Telles F, Bonifaz A, Cognialli R … +3 more , Lustosa BPR, Vicente VA, Ramírez-Marín HA

Curr Fungal Infect Rep · 2022 · PMID 35284035 · Full text

PURPOSE OF REVIEW: Pediatric sporotrichosis has not been sufficiently studied; this review aims to evaluate the risk and prognostic factors related to the development of sporotrichosis associated to this age group. Also,... PURPOSE OF REVIEW: Pediatric sporotrichosis has not been sufficiently studied; this review aims to evaluate the risk and prognostic factors related to the development of sporotrichosis associated to this age group. Also, we want to evaluate the causes of the increased number of cases of sporotrichosis in the pediatric population such as environmental changes in endemic areas, the biodiversity, and virulence among the pathogenic clade causing sporotrichosis in different areas of the globe, and especially the progression of the zoonotic transmission of infections caused by infections, associated to zoonotic transmission in Brazil and other endemic sporotrichosis countries. RECENT FINDINGS: After evaluating a case series of 40 patients, we found that pediatric sporotrichosis in Mexico is mainly caused by which prevails in rural areas and is mainly sapronotically transmitted. In Brazil, the longest and largest pediatric sporotrichosis outbreak is caused by , etiologically related to sick cats, directly from lesions containing a high yeast cell burden. When affecting children and may cause distinct clinical manifestations especially in the onset of the disease and affected anatomical site. In Mexico, most of the patients are successfully treated with potassium iodide, whereas in Brazil, all patients respond to itraconazole. SUMMARY: is the major etiologic agent in Mexico, being sapronotically transmitted, while in Brazil, is only transmitted by cats. In Mexico, the disease prevails in male patients (60%) from rural areas; in Brazil, the disease is more frequent in females (60%) from an urban region. Due to the zoonotic sporotrichosis outbreak in Brazil, the time of evolution seems to be shorter in Brazilian patients than in Mexican patients. Most Brazilian patients presented with facial lesions, including ocular involvement, while in Mexico, most of the children presented upper limbs involvement. In Mexico, treatment with potassium iodide in children was observed to induce faster remission than itraconazole, but controlled studies are lacking to evaluate this versus itraconazole, due to the low number of cases. A comparative study should be designed to evaluate the best and safest antifungal therapy for pediatric sporotrichosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12281-022-00429-x.

Diagnostic Challenges and Emerging Opportunities for the Clinical Microbiology Laboratory.

Keighley C, Garnham K, Harch SAJ … +4 more , Robertson M, Chaw K, Teng JC, Chen SC

Curr Fungal Infect Rep · 2021 · PMID 34178208 · Full text

PURPOSE OF REVIEW: This review summarises the epidemiology of infection and describes contemporary and emerging diagnostic methods for detection and identification of . RECENT FINDINGS: A fifth clade has been described... PURPOSE OF REVIEW: This review summarises the epidemiology of infection and describes contemporary and emerging diagnostic methods for detection and identification of . RECENT FINDINGS: A fifth clade has been described. Diagnostic accuracy has improved with development of selective/differential media for . Advances in spectral databases of matrix-associated laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) systems have reduced misidentification. Direct detection of in clinical specimens using real time PCR is increasingly used, as is whole genome sequencing (WGS) to track nosocomial spread and to study phylogenetic relationships and drug resistance. SUMMARY: is an important transmissible, nosocomial pathogen. The microbiological laboratory diagnostic capacity has extended beyond culture-based methods to include PCR and WGS. Microbiological techniques on the horizon include the use of MALDI-TOF MS for early echinocandin antifungal susceptibility testing (AST) and expansion of the versatile and information-rich WGS methods for outbreak investigation.

Molecular Diagnosis of Yeast Infections.

White PL, Price JS, Cordey A … +1 more , Backx M

Curr Fungal Infect Rep · 2021 · PMID 34178207 · Full text

PURPOSE OF REVIEW: The use of molecular tests to aid the diagnosis of invasive yeast infection, in particular invasive candidosis, has been described for over two decades, yet widespread application is limited, and diagn... PURPOSE OF REVIEW: The use of molecular tests to aid the diagnosis of invasive yeast infection, in particular invasive candidosis, has been described for over two decades, yet widespread application is limited, and diagnosis remains heavily dependent on classical microbiology. This article will review developments from the past decade in attempt to build on existing knowledge. It will highlight clinical performance and limitations while reviewing developments on recognized procedures; it will also provide insight into novel approaches incorporated in response to clinical demand (e.g. and antifungal resistance) or technological advances (e.g. next-generation sequencing). RECENT FINDINGS: Limited methodological standardization and, until recently, unavailability of commercial options have hindered the integration of molecular diagnostics for yeasts. The development of certain, novel commercial methods has received considerable evaluation allowing a greater understanding of individual assay performance, but widespread multicentre evaluation of most commercial kits is lacking. The detection of emerging pathogens (e.g. ) has been enhanced by the development of molecular tests. Molecular methods are providing a better understanding of the mycobiome, mechanisms of resistance and epidemiology/phylogeny. SUMMARY: Despite over two decades of use, the incorporation of molecular methods to enhance the diagnosis of yeast infections remains limited to certain specialist centres. While the development of commercial tests will provide stimulus for broader application, further validation and reduced costs are required. Over the same period of time, PCR has become more widely accepted driven by international efforts to standardize methodology; it is critical that yeast PCR follows suit. Next-generation sequencing will provide significant information on the mycobiome, antifungal resistance mechanism and even broad-range detection directly from the specimen, which may be critical for the molecular detection of yeasts other than species, which is currently limited.

Investigational Agents for the Treatment of Resistant Yeasts and Molds.

Seiler GT, Ostrosky-Zeichner L

Curr Fungal Infect Rep · 2021 · PMID 34075318 · Full text

PURPOSE OF REVIEW: This review summarizes the investigational antifungals in clinical development with the potential to address rising drug resistance patterns. The relevant pharmacodynamics, spectrum of activity, precli... PURPOSE OF REVIEW: This review summarizes the investigational antifungals in clinical development with the potential to address rising drug resistance patterns. The relevant pharmacodynamics, spectrum of activity, preclinical studies, and latest clinical trial data are described. RECENT FINDINGS: Agricultural and medicinal antifungal use has been selected for inherently drug-resistant fungi and acquired resistance mechanisms. The rates of fungal infections and immunocompromised populations continue to grow as few new antifungals have hit the market. Several agents with the potential to address the emergence of multidrug-resistant (MDR) molds and yeasts are in clinical development. SUMMARY: Evolved formulations of echinocandins, polyenes, and triazoles offer less toxicity, convenient dosing, and greater potency, potentially expanding these classes' indications. Ibrexafungerp, olorofim, oteseconazole, and fosmanogepix possess novel mechanisms of actions with potent activity against MDR fungi. Successful clinical development is neither easy nor guaranteed; thus, perpetual efforts to discover new antifungals are needed.

Emergence of Triazole Resistance in spp. in Latin America.

Macedo D, Leonardelli F, Gamarra S … +1 more , Garcia-Effron G

Curr Fungal Infect Rep · 2021 · PMID 34025901 · Full text

PURPOSE OF REVIEW: Azole resistance in spp. is becoming a public health problem worldwide. However, data about this subject is lacking in Latin American countries. This review focuses in the epidemiology and molecular m... PURPOSE OF REVIEW: Azole resistance in spp. is becoming a public health problem worldwide. However, data about this subject is lacking in Latin American countries. This review focuses in the epidemiology and molecular mechanisms of azole resistance in spp. emphasizing in Latin America. Data on stands out because it is the most prevalent spp. pathogen. RECENT FINDINGS: Azole resistance in spp. emergence was linked with intensive use of these antifungals both in the clinical setting and in the environment (as pesticides). Reports on azole-resistant strains are being constantly published in different countries. Molecular mechanisms of resistance mainly involve substitution in the azole target () and/or overexpression of this gene. However, several other non--related mechanisms were described. Moreover, intrinsically resistant cryptic species are starting to be reported as human pathogens. SUMMARY: After a comprehensive literature review, it is clear that azole resistance in spp. is emerging in Latin America and perhaps it is underestimated. All the main molecular mechanisms of azole resistance were described in patients and/or environmental samples. Moreover, one of the molecular mechanisms was described only in South America. Cryptic intrinsic azole-resistant species are also described.

The Lateral Flow Assay for the Diagnosis of Invasive Aspergillosis: an Update.

Jenks JD, Miceli MH, Prattes J … +2 more , Mercier T, Hoenigl M

Curr Fungal Infect Rep · 2020 · PMID 33312332 · Full text

PURPOSE OF REVIEW: To review the data on the lateral flow assay for the diagnosis of invasive Aspergillosis. RECENT FINDINGS: spp. cause a wide spectrum of disease with invasive aspergillosis (IA) as its most severe ma... PURPOSE OF REVIEW: To review the data on the lateral flow assay for the diagnosis of invasive Aspergillosis. RECENT FINDINGS: spp. cause a wide spectrum of disease with invasive aspergillosis (IA) as its most severe manifestation. Early and reliable diagnosis of disease is crucial to decrease associated morbidity and mortality, and enable prompt initiation of treatment for IA. Most recently, non-culture-based tests, such as Aspergillus galactomannan (GM), have been useful in early identification and treatment of patients with IA. However, cost, turnaround time, and variable performance indifferent populations at risk for IA remain significant drawbacks to the use of this test. Several diagnostic tests for IA have been developed, including the sōna GM Lateral flow assay (GM-LFA) rapid test. SUMMARY: The GM-LFA has shown excellent performance for the diagnosis of IA in patients with hematologic malignancy and may be a viable option for settings where ELISA GM testing is not feasible. Further evaluation of the GM-LFA in the non-hematology setting is ongoing, including in solid organ transplant recipients and patients in the intensive care unit.

Clinical Aspects of Immune Damage in Cryptococcosis.

Anjum S, Williamson PR

Curr Fungal Infect Rep · 2019 Sep · PMID 33101578 · Full text

PURPOSE OF REVIEW: To perform an extensive review of recent literature and provide an update on the current epidemiology, clinical features and management of cryptococcal disease with a focus on the differences between p... PURPOSE OF REVIEW: To perform an extensive review of recent literature and provide an update on the current epidemiology, clinical features and management of cryptococcal disease with a focus on the differences between patients depending on their immune status. RECENT FINDINGS: Emerging literature has highlighted the inflammatory pathophysiology and varied manifestations of cryptococcal infections in patients who are apparently healthy but paradoxically have a more critical clinical course compared to their immunosuppressed counterparts. SUMMARY: Non-HIV cryptococcal meningitis has greater mortality compared to that seen in HIV patients. Basic science experiments closely analyzing the underlying pathophysiological response to this infection have demonstrated the predominant role of T cell-mediated inflammatory injury in causing worse clinical outcomes. Further studies are needed to define the need for

Azole-resistant Aspergillus and Echinocandin-resistant Candida - What are the treatment options?

Novak AR, Bradley ME, Kiser TH … +1 more , Mueller SW

Curr Fungal Infect Rep · 2020 Jun · PMID 32699568 · Full text

PURPOSE OF REVIEW: This review summarizes current treatment options for echinocandin-resistant spp. (ERC) and azole-resistant (ARAF), emphasizing recent data, clinical reports, and consensus statements. RECENT FINDING... PURPOSE OF REVIEW: This review summarizes current treatment options for echinocandin-resistant spp. (ERC) and azole-resistant (ARAF), emphasizing recent data, clinical reports, and consensus statements. RECENT FINDINGS: Advances in ERC and ARAF treatment are limited to specific antifungal combinations and dose optimization but remain reliant on amphotericin products. Although novel antifungals may provide breakthroughs in the treatment of resistant fungi, these agents are not yet available. Early identification and appropriate treatment remain a paramount, albeit elusive, task. SUMMARY: When either ERC or ARAF are suspected or proven, amphotericin products remain the cornerstone of initial therapy. For ERC, azoles are de-escalation options for susceptible isolates in stable patients to avoid amphotericin toxicities. Although combination echinocandin with high-dose salvage posaconazole or isavuconazole may be attempted in ARAF, it requires careful consideration following patient stabilization. Future research defining optimal therapies and early identification of ERC and ARAF is of extreme importance.

Combat trauma-related invasive fungal wound infections.

Tribble DR, Ganesan A, Rodriguez CJ

Curr Fungal Infect Rep · 2020 Jun · PMID 32665807 · Full text

PURPOSE OF REVIEW: This review highlights research from the past five years on combat trauma-related invasive fungal wound infections (IFIs) with a focus on risk stratification to aid patient management, microbiology, an... PURPOSE OF REVIEW: This review highlights research from the past five years on combat trauma-related invasive fungal wound infections (IFIs) with a focus on risk stratification to aid patient management, microbiology, and diagnostics. RECENT FINDINGS: A revised classification scheme stratifies wounds into three risk groups: IFI, High Suspicion of IFI, and Low Suspicion of IFI. This stratification is based on persistence of wound necrosis and laboratory fungal evidence, presence of signs/symptoms of deep soft-tissue infections, and the need for antifungals. Use of this classification could allow for prioritization of antifungal therapy. Further, IFIs delay wound healing, particularly when caused by fungi of the order Mucorales. Lastly, molecular sequencing offers promising and complimentary results to the gold standard histopathology. SUMMARY: Optimal management of combat-related IFIs depends on early tissue-based diagnosis with aggressive surgical debridement and concomitant dual antifungal therapy. Further research on clinical decision support tools and rapid diagnostics are needed.

Genetic variation and fungal infection risk: State of the art.

Lionakis MS

Curr Fungal Infect Rep · 2019 Dec · PMID 32523645 · Full text

PURPOSE OF REVIEW: Fungal infections cause significant mortality in patients with acquired immunodeficiencies including AIDS, hematological malignancies, transplantation, and receipt of corticosteroids, biologics or smal... PURPOSE OF REVIEW: Fungal infections cause significant mortality in patients with acquired immunodeficiencies including AIDS, hematological malignancies, transplantation, and receipt of corticosteroids, biologics or small-molecule kinase inhibitors that impair key immune pathways. The contribution of several such pathways in antifungal immunity has been uncovered by inherited immunodeficiencies featuring profound fungal susceptibility. Furthermore, the risk of fungal infection in patients with acquired immunodeficiencies may be modulated by single nucleotide polymorphisms (SNPs) in immune-related genes. This review outlines key features underlying human genetic fungal predisposition. RECENT FINDINGS: The discovery of monogenic disorders that cause fungal disease and the characterization of immune-related gene SNPs that may regulate fungal susceptibility have provided important insights into how genetic variation affects development and outcome of fungal infections in humans. SUMMARY: Recognition of individualized genetic fungal susceptibility traits in humans should help devise precision-medicine strategies for risk assessment, prognostication and treatment of patients with opportunistic fungal infections.

Applying Pharmacogenomics to Antifungal Selection and Dosing: Are We There Yet?

Miller MA, Lee YM

Curr Fungal Infect Rep · 2020 Mar · PMID 32256938 · Full text

PURPOSE OF REVIEW: This review summarizes recent literature for applying pharmacogenomics to antifungal selection and dosing, providing an approach to implementing antifungal pharmacogenomics in clinical practice. RECENT... PURPOSE OF REVIEW: This review summarizes recent literature for applying pharmacogenomics to antifungal selection and dosing, providing an approach to implementing antifungal pharmacogenomics in clinical practice. RECENT FINDINGS: The Clinical Pharmacogenetics Implementation Consortium published guidelines on and voriconazole, with recommendations to use alternative antifungals or adjust voriconazole dose with close therapeutic drug monitoring (TDM). Recent studies demonstrate an association between phenotype and voriconazole levels, clinical outcomes, and adverse events. Additionally, -guided preemptive dose adjustment demonstrated benefit in two prospective studies for prophylaxis. Pharmacokinetic-pharmacodynamic modeling studies have generated proposed voriconazole treatment doses based on phenotypes, with further validation studies needed. SUMMARY: Sufficient evidence is available for implementing -guided voriconazole selection and dosing among select patients at risk for invasive fungal infections. The institution needs appropriate infrastructure for pharmacogenomic testing, integration of results in the clinical decision process, with TDM confirmation of goal trough achievement, to integrate antifungal pharmacogenomics into routine clinical care.

Extrapolating Antifungal Animal Data to Humans - Is it reliable?

Stevens VM, Mueller SW, Reynolds PM … +2 more , MacLaren R, Kiser TH

Curr Fungal Infect Rep · 2020 Mar · PMID 32201545 · Full text

PURPOSE OF REVIEW: This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. RECENT FINDINGS: Animal studies have helped identify AUC... PURPOSE OF REVIEW: This article aimed to review animal models of antifungals and identifies human literature to assess if the extrapolation of results is reliable. RECENT FINDINGS: Animal studies have helped identify AUC/MIC targets for new drugs and formulations such as isavuconazole and delayed release posaconazole that have translated to successful outcomes in humans. Models have also been influential in the identification of possible combination therapies for the treatment of aspergillosis, such as voriconazole and echinocandins. However, challenges are endured with animal models when it comes to replicating the pharmacokinetics of humans which has been exemplified with the newest itraconazole formulation. Additionally, animal models have displayed a survival benefit with the use of iron chelators and amphotericin for mucormycosis which was not demonstrated in humans. SUMMARY: Animal models have been a staple in the development and optimization of antifungal agents. They afford the ability to investigate uncommon diseases, such as invasive fungal infections, that would otherwise take years and many resources to complete. Although there are many benefits of animal models there are also shortcomings. This is why the reliability of extrapolating data from animal models to humans is often scrutinized.

Fungal Infections with Ibrutinib and Other Small-Molecule Kinase Inhibitors.

Zarakas MA, Desai JV, Chamilos G … +1 more , Lionakis MS

Curr Fungal Infect Rep · 2019 Sep · PMID 31555394 · Full text

PURPOSE OF REVIEW: Small molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point toward an increased risk for invasive fungal infection... PURPOSE OF REVIEW: Small molecule kinase inhibitors (SMKIs) have revolutionized the management of malignant and autoimmune disorders. Emerging clinical reports point toward an increased risk for invasive fungal infections (IFIs) in patients treated with certain SMKIs. In this mini-review, we highlight representative examples of SMKIs that have been associated with or are expected to give rise to IFIs. RECENT FINDINGS: The clinical use of the Bruton's tyrosine kinase inhibitor ibrutinib as well as other FDA-approved SMKIs has been associated with IFIs. The fungal infection susceptibility associated with the clinical use of certain SMKIs underscores their detrimental effects on innate and adaptive antifungal immune responses. SUMMARY: The unprecedented development and clinical use of SMKIs is expected to give rise to an expansion of iatrogenic immunosuppressive factors predisposing to IFIs (and other opportunistic infections). Beyond increased clinical surveillance, better understanding of the pathogenesis of SMKI-associated immune dysregulation should help devising improved risk stratification and prophylaxis strategies in vulnerable patients.

(New) Methods for Detection of Resistance in Clinical Samples.

Jenks JD, Spiess B, Buchheidt D … +1 more , Hoenigl M

Curr Fungal Infect Rep · 2019 Sep · PMID 31552129 · Full text

PURPOSE OF REVIEW: The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of with increasing resistance observed against triazol... PURPOSE OF REVIEW: The incidence of invasive aspergillosis has increased substantially over the past few decades, accompanied by a change in susceptibility patterns of with increasing resistance observed against triazole antifungals, including voriconazole and isavuconazole, the most commonly used antifungal agents for the disease. Culture-based methods for determining triazole resistance are still the gold standard but are time consuming and lack sensitivity. We sought to provide an update on non-culture-based methods for detecting resistance patterns to . RECENT FINDINGS: New molecular-based approaches for detecting triazole resistance to , real-time polymerase chain reaction (PCR) to detect mutations to the protein, have been developed which are able to detect most triazole-resistant strains in patients with invasive aspergillosis. SUMMARY: Over the last few years, a number of non-culture-based methods for molecular detection of triazole resistance have been developed that may overcome some of the limitations of culture. These molecular methods are therefore of high epidemiological and clinical relevance, mainly in immunocompromised patients with hematological malignancies, where culture has particularly limited sensitivity. These assays are now able to detect most triazole-resistant strains. Given that resistance rates vary, clinical utility for these assays still depends on regional resistance patterns.

Candidiasis of the Central Nervous System in Neonates and Children with Primary Immunodeficiencies.

Drummond RA, Lionakis MS

Curr Fungal Infect Rep · 2018 Jun · PMID 30393511 · Full text

PURPOSE OF REVIEW: infections of the central nervous system (CNS) are a life-threatening complication of invasive infections that most often affect vulnerable groups of patients, including neonates and children with pri... PURPOSE OF REVIEW: infections of the central nervous system (CNS) are a life-threatening complication of invasive infections that most often affect vulnerable groups of patients, including neonates and children with primary immunodeficiency disorders (PID). Here, we review the currently known risk factors for CNS candidiasis, focusing predominantly on the PID caused by biallelic mutations in . RECENT FINDINGS: How the CNS is protected itself against fungal invasion is poorly understood. CARD9 promotes neutrophil recruitment and function, and is the only molecule shown to be critical for protection against CNS candidiasis in humans thus far. SUMMARY: Fundamental insights into the pathogenesis of CNS candidiasis gained from studying rare CARD9-deficient patients has significant implications for other patients at risk for this disease, such as CARD9-sufficient neonates. These findings will be important for the development of adjunctive immune-based therapies, which are urgently needed to tackle the global burden of invasive fungal diseases.

Role of Serological Tests in the Diagnosis of Mold Infections.

Richardson M, Page I

Curr Fungal Infect Rep · 2018 · PMID 30294405 · Full text

PURPOSE OF REVIEW: To understand the role of antibody detection in the diagnosis of infections caused by filamentous fungi (molds). Rapid and accurate profiling of infection-causing fungal pathogens remains a significant... PURPOSE OF REVIEW: To understand the role of antibody detection in the diagnosis of infections caused by filamentous fungi (molds). Rapid and accurate profiling of infection-causing fungal pathogens remains a significant challenge in modern health care. Classical fungal culture and serology continue to be relevant even though over the past few decades, antigen (biomarker) assays such as ELISA and lateral flow devices have been developed and validated. RECENT FINDINGS: This article reviews the current antibody detection systems (serological tests) for the diagnosis of mold infections associated with pulmonary disease and introduces new developments. Classic and more recently developed serological techniques and their performance characteristics, including immunodiffusion, complement fixation, and ELISA. SUMMARY: The diseases covered are allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, invasive aspergillosis, mucormycosis, diseases caused by filamentous basidiomycetes, infection caused by and pythiosis. Serology remains a cornerstone for fungal diagnostic testing.

Challenges in the Diagnosis of Invasive Fungal Infections in Immunocompromised Hosts.

Antinori S, Corbellino M, Parravicini C

Curr Fungal Infect Rep · 2018 · PMID 32288934 · Full text

PURPOSE OF REVIEW: The expanding population of immunocompromised patients coupled with the recognition of a growing number of different species of fungi responsible for diseases in such hosts makes the diagnosis of invas... PURPOSE OF REVIEW: The expanding population of immunocompromised patients coupled with the recognition of a growing number of different species of fungi responsible for diseases in such hosts makes the diagnosis of invasive fungal infection (IFI) a challenging task. The recent advances and challenges in the diagnosis of IFI in the setting of immunocompromised hosts are reviewed. The advantages and limitations of histopathology and the role of culture-independent methods, such as those based on the use of nucleic acids applied to fresh and formalin-fixed, paraffin-embedded sections, besides culture- and non-culture-based diagnostic methods, to obtain a timely and correct diagnosis of IFI are highlighted. RECENT FINDINGS: The therapeutic implications of identifying the genus and species of the fungus present in the specimen with the molecular diagnostics applied to tissue specimens are reviewed. No method alone is efficient in correctly identifying fungi and it is essential to combine the traditional histochemical staining with molecular methods to achieve a rapid and genus-/species-specific diagnosis of IFI. SUMMARY: We review the recent findings and challenges in the hystopathologic diagnosis of IFI in the setting of immunocompromised hosts. Non method alone is efficient in correctly identify fungi and pathologists should combine classic staining with molecular methods to achieve a rapid and genus/species fungal diagnosis.
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