Curr Fungal Infect Rep
· 2013 Sep · PMID 24040467
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Fungal keratitis remains a challenging and often elusive diagnosis in geographic regions where it is endemic. Marred by delays in diagnosis, the sequelae of corneal fungal infections, though preventable, can be irreversi...Fungal keratitis remains a challenging and often elusive diagnosis in geographic regions where it is endemic. Marred by delays in diagnosis, the sequelae of corneal fungal infections, though preventable, can be irreversible. Recent studies and advances in the arena have broadened the approach and treatment to mycotic keratitis. This review will discuss current diagnostic modalities of fungal keratitis and will particularly focus on treatment regimens. It will also explore future therapeutic models and critique the potential benefit of each.
Curr Fungal Infect Rep
· 2013 Sep · PMID 26512308
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Filamentous basidiomycetes are difficult to identify in the clinical laboratory, mostly due to lack of sporulation, and their role as agents of fungal infection can be difficult to assess. More cases of infection with th...Filamentous basidiomycetes are difficult to identify in the clinical laboratory, mostly due to lack of sporulation, and their role as agents of fungal infection can be difficult to assess. More cases of infection with these agents are being reported as more laboratories gain proficiency with the recognition of their subtle morphologic features and the use of DNA-based methods for identification. Most infections occur in the respiratory tract and sinuses, although brain infection has been reported. Susceptibility testing suggests that these agents will respond well to azole drugs other than fluconazole.
Curr Fungal Infect Rep
· 2012 Dec · PMID 23585916
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Coccidioidomycosis (San Joaquin Valley fever) is a human respiratory disease caused by a soil-borne mold, and is recognized as an intransigent microbial infection by physicians who treat patients with the potentially lif...Coccidioidomycosis (San Joaquin Valley fever) is a human respiratory disease caused by a soil-borne mold, and is recognized as an intransigent microbial infection by physicians who treat patients with the potentially life-threatening, disseminated form of this mycosis. Epidemiological studies based on surveys of skin-test reactivity of people who reside in the endemic regions of the Southwestern US have shown that at least 150,000 new infections occur annually. The clinical spectrum of coccidioidomycosis ranges from an asymptomatic insult to a severe pulmonary disease in which the pathogen may spread from the lungs to the skin, bones, brain and other body organs. Escalation of symptomatic infections and increased cost of long-term antifungal treatment warrant a concerted effort to develop a vaccine against coccidioidomycosis. This review examines recently reported strategies used to generate such a vaccine and summarizes current understanding of the nature of protective immunity to this formidable disease.
Curr Fungal Infect Rep
· 2013 Mar · PMID 23439763
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Invasive aspergillosis (IA) is a feared opportunistic infection for many immuncompromised children resulting in significant morbidity and mortality. Timely diagnosis based on traditional testing modalities and clinical e...Invasive aspergillosis (IA) is a feared opportunistic infection for many immuncompromised children resulting in significant morbidity and mortality. Timely diagnosis based on traditional testing modalities and clinical evaluation has proven to be challenging. Assays designed to measure IA biomarkers such as galactomannan (GM) and beta-D-glucan (BG) represent a potential significant improvement in the ability to diagnose pediatric IA. However, as with any new diagnostic tool, clinicians need to be aware of the operating characteristics of these assays in order to apply them in the appropriate settings. Published adult and pediatric data regarding GM and BG testing are reviewed and guidance regarding the appropriate utility of these assays in children is offered.
Curr Fungal Infect Rep
· 2013 Mar · PMID 23420637
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Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in the immunocompromised. The traditional diagnostic methods of culture and histological examination lack sensitivity and often only mak...Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in the immunocompromised. The traditional diagnostic methods of culture and histological examination lack sensitivity and often only make a diagnosis late when the fungal burden is high, reducing the chances of cure even with the availability of new more potent and less toxic antifungal agents. New non-culture-based serological and PCR assays have been developed. These appear more sensitive and are able to make an earlier diagnosis as compared with traditional diagnostic methods. Early diagnosis is central to reducing IFI-related morbidity and mortality. This review describes the diagnostic potential of the new serological and PCR assays and outlines how these assays have been incorporated into algorithms to improve the management of IFI.
Curr Fungal Infect Rep
· 2012 Dec · PMID 23243480
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Cryptococcus gattii is an environmentally occurring pathogen that is responsible for causing cryptococcosis marked by pneumonia and meningoencephalitis in humans and animals. C. gattii can form long-term associations wit...Cryptococcus gattii is an environmentally occurring pathogen that is responsible for causing cryptococcosis marked by pneumonia and meningoencephalitis in humans and animals. C. gattii can form long-term associations with trees and soil resulting in the production of infectious propagules (spores and desiccated yeast). The ever expanding reports of clinical and environmental isolation of C. gattii in temperate climates strongly imply C. gattii occurs world-wide. The key ability of yeast and spores to enter, survive, multiply, and exit host cells and to infect immunocompetent hosts distinguishes C. gattii as a primary pathogen and suggest evolution of C. gattii pathogenesis as a result of interaction with plants and other organisms in its environmental niche. Here we summarize the historical literature on C. gattii and recent literature supporting the world-wide occurrence of the primary pathogen C. gattii.
Curr Fungal Infect Rep
· 2012 Dec · PMID 29118894
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Aspergillosis has emerged as an important contributor to infection-related morbidity and mortality in susceptible populations. This comes at a time when we are also seeing an increase in the vulnerable populations themse...Aspergillosis has emerged as an important contributor to infection-related morbidity and mortality in susceptible populations. This comes at a time when we are also seeing an increase in the vulnerable populations themselves. At the same time, some parts of the world are reporting an increased incidence of aspergillosis refractory to triazole therapy. Resistance to triazole drugs may have major implications for aspergillosis management since our antifungal armamentarium is limited. This review gives an overview of populations at risk of developing aspergillosis and highlights resistance mechanisms that may contribute to morbidity and mortality in these vulnerable populations.
Curr Fungal Infect Rep
· 2012 Mar · PMID 23087779
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Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surf...Most fungal infections in humans occur in the setting of iatrogenic immunosuppression or HIV infection. In the absence of these factors, fungi cause mild, self-limited infections that typically involve mucocutaneous surfaces. Hence, when persistent or recurrent mucocutaneous infections (chronic mucocutaneous candidiasis [CMC]) or invasive fungal infections (IFIs) develop in a "normal" host, they are indicative of genetic defects causing innate or adaptive immune dysfunction. In this review, recent developments concerning genetic and immunologic factors that affect the risk for IFIs and CMC are critically discussed.
Curr Fungal Infect Rep
· 2012 Sep · PMID 26526658
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Increases in susceptible patient populations and advances in identification methods have resulted in the continued recognition of novel yeasts as agents of human infection. Most of these agents are members of the well-re...Increases in susceptible patient populations and advances in identification methods have resulted in the continued recognition of novel yeasts as agents of human infection. Most of these agents are members of the well-recognized genera , , , and . Some of these agents are "cryptic species," members of species complexes, and may not be detectable using classical carbohydrate assimilation-based methods of yeast identification. Such species require DNA- or MALDI-based methods for correct identification, although sporadic isolates may not routinely require delineation to the individual species level. The coming end of the fungal taxonomy rules requiring separate names for sexual and asexual forms of the same fungus will hopefully allow greater clarity, as names for medically important yeast can now be based on the needs of the medical mycology community and the common goal of better communication between laboratory and clinician.
Pfaller MA, Castanheira M, Lockhart SR
… +1 more, Jones RN
Curr Fungal Infect Rep
· 2012 Jun · PMID 40093589
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is widely acknowledged to be an important and potentially antifungal resistant cause of hematogenously disseminated candidiasis (HDC). In the United States (US) both the frequency of as a cause of HDC and in vitro resis...is widely acknowledged to be an important and potentially antifungal resistant cause of hematogenously disseminated candidiasis (HDC). In the United States (US) both the frequency of as a cause of HDC and in vitro resistance to fluconazole has increased steadily since 1992. Although this species is generally considered to be less virulent than , recent findings suggest that gain of function (GOF) mutations in the transcriptional regulator CgPdr1p results not only in broad resistance to azole antifungals but also an increase in both fitness and virulence in animal models. Furthermore, case reports and case series suggest the emergence of multidrug resistance (MDR) in this species. Recent data from multicenter surveys conducted in the US have demonstrated the emergence of co-resistance to both azoles and echinocandins in clinical isolates of . These findings are highlighted in an effort to bring attention to this important development.
Curr Fungal Infect Rep
· 2011 Dec · PMID 22389746
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This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three p...This review provides an overview of Cryptococcus neoformans immunology and focuses on the pathogenesis of Cryptococcus-related paradoxical immune reconstitution inflammatory syndrome (IRIS). Cryptococcal IRIS has three phases: (1) before antiretroviral therapy (ART), with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance; (2) during initial ART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and (3) at IRIS, a cytokine storm with a predominant type-1 helper T-cell (Th(1)) interferon-gamma (IFN-γ) response. Understanding IRIS pathogenesis allows for risk stratification and customization of HIV/AIDS care. In brief, persons at high IRIS risk may benefit from enhancing microbiologic clearance by use of adjunctive agents in combination with amphotericin, prolonging initial induction therapy, and/or increasing the initial consolidation antifungal therapy dose to at least 800 mg of fluconazole daily until the 2-week CSF culture is known to be sterile. Prophylactic anti-inflammatory therapies or undue delay of ART initiation in an attempt to prevent IRIS is unwarranted and may be dangerous.
Sifuentes-Osornio J, Corzo-León DE, Ponce-de-León LA
Curr Fungal Infect Rep
· 2012 Mar · PMID 22363832
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The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure act...The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome.
Curr Fungal Infect Rep
· 2010 Dec · PMID 21660222
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The use of indwelling medical devices is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. Fungal biofilms have e...The use of indwelling medical devices is rapidly growing and is often complicated by infections with biofilm-forming microbes that are resistant to antimicrobial agents and host defense mechanisms. Fungal biofilms have emerged as a clinical problem associated with these medical device infections, causing significant morbidity and mortality. This review discusses the recent advances in the understanding of fungal biofilms, including the role of fungal surface components in adherence, gene expression, and quorum sensing in biofilm formation. We propose novel strategies for the prevention or eradication of microbial colonization of medical prosthetic devices.
Curr Fungal Infect Rep
· 2011 Jun · PMID 32284787
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Both the incidence of invasive fungal infections and the number of antifungal agents available to clinicians have expanded significantly over the past two decades. Successes with pharmacokinetic and pharmacodynamic evalu...Both the incidence of invasive fungal infections and the number of antifungal agents available to clinicians have expanded significantly over the past two decades. Successes with pharmacokinetic and pharmacodynamic evaluations of other antimicrobial agents in animal models and their clinical correlations with patient outcomes have led to an increased number of studies evaluating both old and new antifungal agents. Recently, animal models have successfully defined target pharmacodynamic indices for many antifungal agents and fungal infections, but validation of these targets in human studies is frequently lacking. This article evaluates the potential pros and cons of extrapolating to humans the animal data on antifungal pharmacodynamics.
Curr Fungal Infect Rep
· 2010 Dec · PMID 20976286
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It has been long appreciated that protective immunity against fungal pathogens is dependent on activation of cellular adaptive immune responses represented by T lymphocytes. The T-helper (Th)1/Th2 paradigm has proven to...It has been long appreciated that protective immunity against fungal pathogens is dependent on activation of cellular adaptive immune responses represented by T lymphocytes. The T-helper (Th)1/Th2 paradigm has proven to be essential for the understanding of protective adaptive host responses. Studies that have examined the significance of regulatory T cells in fungal infection, and the recent discovery of a new T-helper subset called Th17 have provided crucial information for understanding the complementary roles played by the various T-helper lymphocytes in systemic versus mucosal antifungal host defense. This review provides an overview of the role of the various T-cell subsets during fungal infections and the reciprocal regulation between the T-cell subsets contributing to the tailored host response against fungal pathogens.
Curr Fungal Infect Rep
· 2010 May · PMID 20574543
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Given the substantial morbidity and mortality related to invasive fungal infections, treatment with a combination of antifungal agents is often considered. A growing body of literature from in vitro studies, animal model...Given the substantial morbidity and mortality related to invasive fungal infections, treatment with a combination of antifungal agents is often considered. A growing body of literature from in vitro studies, animal models, and clinical experience provides data evaluating this approach. This review describes combination antifungal strategies for the management of cryptococcal meningitis, invasive candidiasis, invasive aspergillosis, and rare mold infections. The potential effects that sequencing and timing have on the efficacy of such approaches are discussed, with a focus on recent clinical data in this arena.
Curr Fungal Infect Rep
· 2010 Jun · PMID 20502511
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Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic...Pulmonary infections caused by Aspergillus species are associated with significant morbidity and mortality in immunocompromised patients. Although the treatment of pulmonary fungal infections requires the use of systemic agents, aerosolized delivery is an attractive option in prevention because the drug can concentrate locally at the site of infection with minimal systemic exposure. Current clinical evidence for the use of aerosolized delivery in preventing fungal infections is limited to amphotericin B products, although itraconazole, voriconazole, and caspofungin are under investigation. Based on conflicting results from clinical trials that evaluated various amphotericin B formulations, the routine use of aerosolized delivery cannot be recommended. Further research with well-designed clinical trials is necessary to elucidate the therapeutic role and risks associated with aerosolized delivery of antifungal agents. This article provides an overview of aerosolized delivery systems, the intrapulmonary pharmacokinetic properties of aerosolized antifungal agents, and key findings from clinical studies.
Downey LC, Smith PB, Benjamin DK
… +1 more, Cohen-Wolkowiez M
Curr Fungal Infect Rep
· 2010 Mar · PMID 20454602
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Neonatal candidiasis is serious and often fatal. Blood culture, the standard for diagnosis, has a sensitivity of 50% or less, and isolate speciation and susceptibility takes several days. This review explores recent adva...Neonatal candidiasis is serious and often fatal. Blood culture, the standard for diagnosis, has a sensitivity of 50% or less, and isolate speciation and susceptibility takes several days. This review explores recent advances in Candida detection using various diagnostic strategies.
Understanding fungal pathogenesis and host-pathogen immune interaction at various stages of infection is critical to examine strategies for bolstering antifungal immune defenses. Recombinant myeloid growth factors, espec...Understanding fungal pathogenesis and host-pathogen immune interaction at various stages of infection is critical to examine strategies for bolstering antifungal immune defenses. Recombinant myeloid growth factors, especially granulocyte-macrophage colony-stimulating factor and the protagonist T helper (Th) 1 cytokine, interferon-γ, are most frequently used in patients with refractory invasive aspergillosis. These cytokines are given alone or in combination and have also been used together in neutropenic patients receiving donor granulocyte transfusions. Recently, a number of investigators have presented provoking data regarding auxiliary effect of conventional antifungal drugs on hosts' immune response and pathogen's susceptibility for antifungal immune defenses. Antifungal immunotherapy and its ameliorative role in treatment for disease will need clinical trials that 1) consider well-characterized fungal disease; 2) illustrate underlying immune defect(s) (such as Th1 vs Th2, vs Th17 and functional status of natural killer and effector scavenger cells); 3) include a more specific patient population; 4) include standardized antifungal drug therapy; and importantly 5) consider its impact on hosts' immune response and changes in pathogen's susceptibility and virulence. At present, immunotherapy is reserved for patients with life-threatening invasive fungal disease in whom conventional antifungal drug therapy has failed, or for patients with advanced fungal disease and with factors associated with high probability of failure of conventional therapy alone.
Curr Fungal Infect Rep
· 2009 Sep · PMID 20161440
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Antifungal resistance caused by mutations of the drug target, overexpression of the drug target, and drug efflux by the upregulation of transporters is increasingly common. Recently our understanding of fungal drug resis...Antifungal resistance caused by mutations of the drug target, overexpression of the drug target, and drug efflux by the upregulation of transporters is increasingly common. Recently our understanding of fungal drug resistance has been advanced by the identification of three key transcriptional regulators of resistance: Tac1p, Upc2p, and Mrr1p. The discovery of hyperactive variants of these regulators in resistant clinical isolates confirms the importance of transcriptional regulation in the development of antifungal resistance. Alternative mechanisms of drug resistance including aneuploidy and biofilm formation have recently been documented in fungi; as well as the phenomenon of drug tolerance. Characterization of the transcriptional regulation of fungal drug resistance and the identification of novel mechanisms of resistance has implications for current therapy and for the development of future antifungal drugs.