The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ashraf S. Ibrahim - One of the best experts on this subject based on the ideXlab platform.
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Mucormycosis and Entomophthoramycosis (Zygomycosis)
Essentials of Clinical Mycology, 2010Co-Authors: Ashraf S. Ibrahim, Scott G. Filler, John E Edwards, Brad SpellbergAbstract:Previously the term Zygomycosis was used to refer to infections caused by fungi belonging to the phylum Zygomycota, class Zygomycetes, orders Mucorales and Entomophthorales. However, a more recent classification based on molecular phylogenetic studies of rRNA, tef1, and rpb1, has abolished the class Zygomycetes and instead distributes fungi previously in the phylum Zygomycota into the phylum Glomeromycota and four subphyla, including Mucoromycotina, Kickxellomycotina, Zoopagomycotina, and Entomophthoromycotina (Table 1) [1]. Therefore, the term Zygomycosis, which has been used by clinicians and mycologists for decades, is no longer relevant to fungal taxonomy. Both terms, mucormycosis and Zygomycosis, are used throughout this book, reflecting the recent changes in nomenclature and the slower evolution of clinical parlance.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-beta-D-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-β-d-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
Thomas J. Walsh - One of the best experts on this subject based on the ideXlab platform.
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Zygomycosis in neonates an uncommon but life threatening infection
American Journal of Perinatology, 2009Co-Authors: Emmanuel Roilides, Theoklis E Zaoutis, Aspasia Katragkou, Daniel K Benjamin, Thomas J. WalshAbstract:We systematically reviewed all published cases of Zygomycosis, an increasingly important infection with high mortality, in neonates. We searched PubMed and individual references for English publications of single cases or case series of neonatal (0 to 1 month) Zygomycosis. Cases were included if they fulfilled prespecified criteria. Fifty-nine cases were published through July 2007. Most of the infants (77%) were premature. The most common sites of Zygomycosis were gastrointestinal (54%) and cutaneous (36%) diseases. This pattern differs from sinopulmonary and rhinocerebral patterns of older children. Fifty-six percent of cases were diagnosed by histology only and 44% by histology and culture. RHIZOPUS spp. were isolated from 18/25 (72%) cases. Thirty-seven percent of patients received no antifungal therapy. Thirty-two (54%) neonates underwent surgery with (39%) or without (15%) antifungal agents. Overall mortality was 64%. A higher fraction of neonates treated with amphotericin B and surgery survived than those who received no therapy (70% versus 5%). Zygomycosis is a life-threatening infection in neonates with a distinct pattern of gastrointestinal and cutaneous involvement and high mortality. Combination of amphotericin B and surgery was common management strategy in survivors.
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invasive Zygomycosis in neonates and children
Clinical Microbiology and Infection, 2009Co-Authors: Emmanuel Roilides, Theoklis E Zaoutis, Thomas J. WalshAbstract:Invasive Zygomycosis in neonates and children has both similarities to and differences from that in adults. We searched PubMed and individual references for English-language reports of single cases or case series of neonatal (<1 month) and paediatric (< or =18 years) Zygomycosis and compared the results with published results in adults. Cases were included if they fulfilled pre-specified criteria. A total of 59 cases of neonatal Zygomycosis were reported to July 2007; 157 paediatric cases were published up to 2004 and an additional 30 paediatric cases were reported more recently. Prematurity was a major underlying factor among neonatal cases. The most common manifestations of Zygomycosis were gastrointestinal (54%) and cutaneous (36%). This pattern differs from the sinopulmonary and rhinocerebral patterns typical in older children and adults. Overall mortality was 64% in neonates, 56% in children and 53% in adults. A tendency for dissemination was higher in neonates than adults. Dissemination and young age (<1 year) were independent risk factors for death in children. Most patients who survived received antifungal therapy. Surgery combined with antifungal therapy was a protective factor against death. Most neonates and children who survived had received an amphotericin B formulation. Zygomycosis is a life-threatening infection in children and neonates with differing patterns of involvement in individuals of different ages. The most common management strategy in survivors involved a combination of amphotericin B and surgery.
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what is the role of combination therapy in management of Zygomycosis
Clinical Infectious Diseases, 2008Co-Authors: Thomas J. Walsh, Dimitrios P KontoyiannisAbstract:In several oncology and transplantation centers across the United States, invasive Zygomycosis has been reported with increased frequency in the form of severe, frequently lethal sinopulmonary and disseminated infection [1-4]. Zygomycetes have the propensity to cause infection in a broad range of patients in whom different patterns of infection prevail [1]. In patients with poorly controlled diabetes mellitus, sino-orbital and rhinocerebral infection are the most common patterns, and in neutropenic patients, pulmonary and disseminated cases of Zygomycosis are common. Crude mortality with antifungal therapy is ~40% among patients with Zygomycosis [1]. Hematological malignancy and hematopoietic stem cell transplantation have more ominous prognoses, with an associated mortality of 66%-91% [1, 2]. For nearly 50 years, the management of Zygomycosis has depended on the triad of amphotericin B deoxycholate (AmB) therapy, surgical resection, and reversal of underlying host deficits. The past decade has been marked by the development of new pharmacological, immunomodulatory, and conceptual advances that may help in the treatment of this uncommon but lethal infection. Among the therapeutic developments are the lipid formulations of AmB [5, 6], posaconazole [7, 8], deferasirox [9, 10], the echinocandins to be used in combination with AmB [11, 12], and the recombinant cytokines, such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor [13, 14]. The role of these agents alone, in combination, or in sequential use for the treatment of Zygomycosis has important implications for outcome in patients with these life-threatening infections. Laboratory and clinical studies of 2 combined antifungal agents for the treatment of infections caused by Cryptococcus neoformans [15-17], Candida species [18, 19], and Aspergillus species [20-23] demonstrated a beneficial role for some but not all combinations. Some combina-
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successful medical management of isolated renal Zygomycosis case report and review
Clinical Infectious Diseases, 1998Co-Authors: David E Weng, Wyndham H Wilson, Richard F Little, Thomas J. WalshAbstract:We describe the medical management of isolated renal Zygomycosis in an adult patient with AIDS during chemotherapy for AIDS-related lymphoma. After initial presentation during the first cycle of chemotherapy, the infection was contained within the kidney following recovery of the neutrophil count without medical or surgical intervention. Since he was not considered to be a candidate for nephrectomy, his infection was treated with amphotericin B lipid complex during subsequent chemotherapy. Neutropenia was minimized by the addition of cytokine support therapy with granulocyte colony-stimulating factor and reduced doses of chemotherapy. Following this strategy, his lymphoma completely resolved, and renal Zygomycosis was controlled. At the time of this writing, he had been in complete remission for 18 months without evidence of progressive fungal infection. This report and our literature review indicate that isolated renal Zygomycosis can be associated with a favorable prognosis, occurs with greatest frequency in patients with AIDS, is associated with parenteral access, and may be managed by medical therapy alone.
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disseminated Zygomycosis in a neutropenic patient successful treatment with amphotericin b lipid complex and granulocyte colony stimulating factor
Clinical Infectious Diseases, 1997Co-Authors: Corina E Gonzalez, Daniel R Couriel, Thomas J. WalshAbstract:Disseminated Zygomycosis in persistently neutropenic patients has been almost uniformly fatal despite aggressive surgical and medical management. We describe a neutropenic patient with disseminated Zygomycosis that involved the lungs and kidneys and was successfully treated with amphotericin B lipid complex and granulocyte colony-stimulating factor, followed by suppressive therapy with amphotericin B for 1 year. This approach preserved the patient's renal function and restored systemic host defenses. The single pulmonary lesion was resected, but no resection of renal tissue was attempted because of the bilateral extension of the renal lesions. After a 1-year period of follow-up without antifungal therapy, the patient's condition remains stable, and there has been no relapse of the infection.
Dimitrios P Kontoyiannis - One of the best experts on this subject based on the ideXlab platform.
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delaying amphotericin b based frontline therapy significantly increases mortality among patients with hematologic malignancy who have Zygomycosis
Clinical Infectious Diseases, 2008Co-Authors: Georgios Chamilos, Russell E Lewis, Dimitrios P KontoyiannisAbstract:Background Zygomycosis is an emerging opportunistic mycosis among immunocompromised patients with a particularly poor prognosis. Methods We analyzed the impact of delaying effective amphotericin B-based therapy on outcome among 70 consecutive patients with hematologic malignancy who had Zygomycosis in our institution during the period 1989-2006. We used classification and regression tree analysis to identify the mortality breakpoint between early and delayed treatment. Results Delayed amphotericin B-based therapy (i.e., initiating treatment >/=6 days after diagnosis) resulted in a 2-fold increase in mortality rate at 12 weeks after diagnosis, compared with early treatment (82.9% vs. 48.6%); this remained constant across the years of the study and was an independent predictor of poor outcome (odds ratio, 8.1; 95% confidence interval, 1.7-38.2; P = .008) in multivariate analysis. Active malignancy (P = .003) and monocytopenia (P =.01) at the time of diagnosis of infection were also independently associated with a poor outcome, whereas salvage posaconazole-based therapy (P=.01) and neutrophil recovery (P = .009) were predictive of a favorable outcome. Conclusions Because discriminating between Zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for Zygomycosis.
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what is the role of combination therapy in management of Zygomycosis
Clinical Infectious Diseases, 2008Co-Authors: Thomas J. Walsh, Dimitrios P KontoyiannisAbstract:In several oncology and transplantation centers across the United States, invasive Zygomycosis has been reported with increased frequency in the form of severe, frequently lethal sinopulmonary and disseminated infection [1-4]. Zygomycetes have the propensity to cause infection in a broad range of patients in whom different patterns of infection prevail [1]. In patients with poorly controlled diabetes mellitus, sino-orbital and rhinocerebral infection are the most common patterns, and in neutropenic patients, pulmonary and disseminated cases of Zygomycosis are common. Crude mortality with antifungal therapy is ~40% among patients with Zygomycosis [1]. Hematological malignancy and hematopoietic stem cell transplantation have more ominous prognoses, with an associated mortality of 66%-91% [1, 2]. For nearly 50 years, the management of Zygomycosis has depended on the triad of amphotericin B deoxycholate (AmB) therapy, surgical resection, and reversal of underlying host deficits. The past decade has been marked by the development of new pharmacological, immunomodulatory, and conceptual advances that may help in the treatment of this uncommon but lethal infection. Among the therapeutic developments are the lipid formulations of AmB [5, 6], posaconazole [7, 8], deferasirox [9, 10], the echinocandins to be used in combination with AmB [11, 12], and the recombinant cytokines, such as granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor [13, 14]. The role of these agents alone, in combination, or in sequential use for the treatment of Zygomycosis has important implications for outcome in patients with these life-threatening infections. Laboratory and clinical studies of 2 combined antifungal agents for the treatment of infections caused by Cryptococcus neoformans [15-17], Candida species [18, 19], and Aspergillus species [20-23] demonstrated a beneficial role for some but not all combinations. Some combina-
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drosophila melanogaster as a model host to dissect the immunopathogenesis of Zygomycosis
Proceedings of the National Academy of Sciences of the United States of America, 2008Co-Authors: Georgios Chamilos, Russell E Lewis, Lianchun Xiao, Tomasz Zal, Michel Gilliet, Georg Halder, Dimitrios P KontoyiannisAbstract:Zygomycosis is an emerging frequently fatal opportunistic mycosis whose immunopathogenesis is poorly understood. We developed a Zygomycosis model by injecting Drosophila melanogaster flies with a standardized amount of fungal spores from clinical Zygomycetes isolates to study virulence and host defense mechanisms. We found that, as opposed to most other fungi, which are nonpathogenic in D. melanogaster (e.g., Aspergillus fumigatus), Zygomycetes rapidly infect and kill wild-type flies. Toll-deficient flies exhibited increased susceptibility to Zygomycetes, whereas constitutive overexpression of the antifungal peptide Drosomycin in transgenic flies partially restored resistance to Zygomycosis. D. melanogaster Schneider 2 phagocytic cells displayed decreased phagocytosis and caused less hyphal damage to Zygomycetes compared with that to A. fumigatus. Furthermore, phagocytosis-defective eater mutant flies displayed increased susceptibility to Zygomycetes infection. Classic enhancers of Zygomycetes virulence in humans, such as corticosteroids, increased iron supply, and iron availability through treatment with deferoxamine dramatically increased Zygomycetes pathogenicity in our model. In contrast, iron starvation induced by treatment with the iron chelator deferasirox significantly protected flies infected with Zygomycetes. Whole-genome expression profiling in wild-type flies after infection with Zygomycetes vs. A. fumigatus identified genes selectively down-regulated by Zygomycetes, which act in pathogen recognition, immune defense, stress response, detoxification, steroid metabolism, or tissue repair or have unknown functions. Our results provide insights into the factors that mediate host–pathogen interactions in Zygomycosis and establish D. melanogaster as a promising model to study this important mycosis.
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invasive Zygomycosis update on pathogenesis clinical manifestations and management
Infectious Disease Clinics of North America, 2006Co-Authors: Dimitrios P Kontoyiannis, Russell E LewisAbstract:Zygomycosis is an increasingly common infection in immunocompromised patients. Advances in the understanding of Zygomycetes pathobiology and the introduction of new drugs with improved activity and tolerability for treatment of Zygomycosis have improved the prospects of effectively controlling this devastating infection. Further reductions in mortality will require improved diagnostic and novel therapeutic approaches for this group of aggressive opportunistic molds.
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posaconazole is effective as salvage therapy in Zygomycosis a retrospective summary of 91 cases
Clinical Infectious Diseases, 2006Co-Authors: Jo Anne H Van Burik, Roberta S Hare, Howard F Solomon, M L Corrado, Dimitrios P KontoyiannisAbstract:To evaluate the activity of posaconazole for treatment of Zygomycosis, a disease for which therapeutic options are limited, we conducted a retrospective study including 91 patients with Zygomycosis (proven Zygomycosis, 69 patients; probable Zygomycosis, 22 patients). Patients had infection that was refractory to prior antifungal treatment (n=81) or were intolerant of such treatment (n=10) and participated in the compassionate-use posaconazole (800 mg/day) program. The rate of success (i.e., either complete or partial response) at 12 weeks after treatment initiation was 60%, and 21% of patients had stable disease. The overall high success and survival rates reported here provide encouraging data regarding posaconazole as an alternative therapy for Zygomycosis.
Cameron M Douglas - One of the best experts on this subject based on the ideXlab platform.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-beta-D-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-β-d-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
John E Edwards - One of the best experts on this subject based on the ideXlab platform.
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Mucormycosis and Entomophthoramycosis (Zygomycosis)
Essentials of Clinical Mycology, 2010Co-Authors: Ashraf S. Ibrahim, Scott G. Filler, John E Edwards, Brad SpellbergAbstract:Previously the term Zygomycosis was used to refer to infections caused by fungi belonging to the phylum Zygomycota, class Zygomycetes, orders Mucorales and Entomophthorales. However, a more recent classification based on molecular phylogenetic studies of rRNA, tef1, and rpb1, has abolished the class Zygomycetes and instead distributes fungi previously in the phylum Zygomycota into the phylum Glomeromycota and four subphyla, including Mucoromycotina, Kickxellomycotina, Zoopagomycotina, and Entomophthoromycotina (Table 1) [1]. Therefore, the term Zygomycosis, which has been used by clinicians and mycologists for decades, is no longer relevant to fungal taxonomy. Both terms, mucormycosis and Zygomycosis, are used throughout this book, reflecting the recent changes in nomenclature and the slower evolution of clinical parlance.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-beta-D-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
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caspofungin inhibits rhizopus oryzae 1 3 β d glucan synthase lowers burden in brain measured by quantitative pcr and improves survival at a low but not a high dose during murine disseminated Zygomycosis
Antimicrobial Agents and Chemotherapy, 2005Co-Authors: Ashraf S. Ibrahim, John E Edwards, Brad Spellberg, Joel Bowman, Valentina Avanessian, Keturah Brown, Cameron M DouglasAbstract:Rhizopus oryzae is the most common cause of Zygomycosis, a life-threatening infection that usually occurs in patients with diabetic ketoacidosis. Despite standard therapy, the overall rate of mortality from Zygomycosis remains >50%, and new strategies for treatment are urgently needed. The activities of caspofungin acetate (CAS) and other echinocandins (antifungal inhibitors of the synthesis of 1,3-β-d-glucan synthase [GS]) against the agents of Zygomycosis have remained relatively unexplored, especially in animal models of infection. We found that R. oryzae has both an FKS gene, which in other fungi encodes a subunit of the GS synthesis complex, and CAS-susceptible, membrane-associated GS activity. Low-dose but not high-dose CAS improved the survival of mice with diabetic ketoacidosis infected with a small inoculum but not a large inoculum of R. oryzae. Fungal burden, assessed by a novel quantitative PCR assay, correlated with increasing inocula and progression of disease, particularly later in the infection, when CFU counts did not. CAS decreased the brain burden of R. oryzae when it was given prophylactically but not when therapy was started after infection. These results indicate that CAS has significant but limited activity against R. oryzae in vivo and demonstrates an inverse dose-response effect. The potential for CAS to play a role in combination therapy against Zygomycosis merits further investigation.
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Acute Invasive Rhinocerebral Zygomycosis in an Otherwise Healthy Patient: Case Report and Review
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1995Co-Authors: Allen B. Radner, Mallory D. Witt, John E EdwardsAbstract:A previously healthy 19-year-old man developed rapidly progressive invasive rhinocerebral Zygomycosis due to Apophysomyces elegans. He required extensive surgery and prolonged treatment with high-dose i.v. amphotericin B for cure. This is only the third reported case of acute invasive rhinocerebral Zygomycosis in an otherwise healthy patient and the first reported case of infection due to A. elegans in any patient. We review the literature and clinical spectrum of rhinocerebral Zygomycosis in otherwise healthy patients and discuss the recently recognized association between A. elegans and Zygomycosis in immunocompetent patients.
