Scott Filler - Academia.edu (original) (raw)
Papers by Scott Filler
Clinical Infectious Diseases, 2006
The incidence of disseminated candidiasis has increased dramatically over the past several decade... more The incidence of disseminated candidiasis has increased dramatically over the past several decades. Fortunately, in recent years, a variety of new antifungal agents have become available to treat these infections. On the basis of efficacy, safety, and cost considerations, fluconazole is the agent of choice for the empirical treatment of disseminated candidiasis in nonneutropenic, hemodynamically stable patients, unless a patient is suspected to be infected with an azole-resistant species (i.e., Candida glabrata or Candida krusei). For hemodynamically unstable or neutropenic patients, agents with broader species coverage, such as polyenes, echinocandins, or, possibly, voriconazole, are preferred for empirical treatment of candidemia. Modification of the initial, empirical regimen depends on the response to therapy and the subsequent identification of the species of the offending pathogen. Echinocandins or high-dose polyenes are preferred for the treatment of infections with C. glabrata or C. krusei. Central venous catheters should be removed from all patients who have disseminated candidiasis, if feasible, and antifungal therapy should be administered to all patients who have candidemia or proven candidiasis. Candida organisms are opportunistic fungal pathogens that have become a major cause of nosocomial infections in the United States and worldwide. Candida species have become the third most common nosocomial bloodstream isolates and are exceeded in frequency only by coagulase-negative staphylococci and Staphylococcus aureus [1]. In the United States, the annual incidence of blood culture-confirmed candidemia reported in populationbased surveys is ∼10 cases/100,000 population [2, 3]. However, because blood cultures are insensitive for the diagnosis, up to half of the cases of disseminated candidiasis (defined as candidal infection in sterile target organs, with or without positive blood culture results) are never microbiologically confirmed. Therefore, estimates of disease frequency based on positive blood culture results are artificially low, and an annual incidence of у20 cases/ 100,000 population (у60,000 cases/year in the United States) is likely to be more accurate [4]. Although Candida species are opportunistic pathogens, the majority of patients who develop disseminated candidiasis are not immunosuppressed in the classical sense [5]. Rather, the predominant risk factors for disseminated candidiasis are common iatrogenic and/or nosocomial factors (table 1). Given the
When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oro... more When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invad...
Clinical Infectious Diseases, 2004
Candida species are the most common cause of fungal infections. Candida species produce infection... more Candida species are the most common cause of fungal infections. Candida species produce infections that range from non-life-threatening mucocutaneous illnesses to invasive processes that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. These guidelines summarize current knowledge about treatment of multiple forms of candidiasis for the Infectious Diseases Society of America (IDSA). Throughout this document, treatment recommendations are rated according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the supporting evidence and quality of the underlying data (table 1). This document covers the following 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. However, susceptibility testing of fungi is not considered a routine testing procedure in many laboratories, is not always promptly available, and is not universally considered as the standard of care. Knowledge of the infecting species, however, is highly predictive of likely susceptibility and can be used as a guide to therapy. The guidelines review the available infor
Clinical Infectious …
Featured in New York Times "Searching the Web for Flu Outbreaks" November 28, 2008 Usin... more Featured in New York Times "Searching the Web for Flu Outbreaks" November 28, 2008 Using Internet Searches for Influenza Surveillance Philip M. Polgreen, Yiling Chen, David M. Pennock, and Forrest D. Nelson One study, published by the journal Clinical Infectious ...
Chest, 2001
Because of the rapidly increasing incidence of serious candidal infections, a consensus conferenc... more Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.
New England Journal of Medicine, 2006
Eukaryotic Cell, 2002
Candida albicans is an important pathogen of immunocompromised patients which grows with true hyp... more Candida albicans is an important pathogen of immunocompromised patients which grows with true hyphal, pseudohyphal, and yeast morphologies. The dynamics of cell cycle progression are markedly different in true hyphal relative to pseudohyphal and yeast cells, including nuclear movement and septin ring positioning. In Saccharomyces cerevisiae, two forkhead transcription factors (ScFKH1 and ScFKH2) regulate the expression of B-cyclin genes. In
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2002
The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was exami... more The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was examined in Adult AIDS Clinical Trial Group (AACTG) 722, a virology substudy of AACTG 323: a phase 4 randomized study designed to examine the use of chronic suppressive versus episodic fluconazole therapy. The primary analysis used a case-control sampling scheme with two controls per "case" (subjects that developed an OI) matched by gender, age, and time on study. Forty-five cases and matched controls were identified and used in the analysis. Study 722 accrued 518 subjects between 5/97 and 11/99. Forty-five subjects developed serious OIs or refractory candidiasis. Median baseline CD4 count was 24 cell/mm3 for cases and 46 for controls (p =.003). Median viral load (VL) was 5.02 log10 copies/mL for cases and 4.08 for controls (p =.002). Multivariate analysis found four independent variables associated with time to OI: baseline VL and CD4 (RR = 2.2 per log increment and 6.0 per 50-cell increment, respectively), a one log increase in VL at any time (RR = 15), and history of an OI (RR = 5.2). VL and changes in VL were independently associated with risk of development of OIs in a prospective study and should be considered by clinicians when assessing patients for risk of OI.
Clinical Infectious Diseases, 2006
The incidence of disseminated candidiasis has increased dramatically over the past several decade... more The incidence of disseminated candidiasis has increased dramatically over the past several decades. Fortunately, in recent years, a variety of new antifungal agents have become available to treat these infections. On the basis of efficacy, safety, and cost considerations, fluconazole is the agent of choice for the empirical treatment of disseminated candidiasis in nonneutropenic, hemodynamically stable patients, unless a patient is suspected to be infected with an azole-resistant species (i.e., Candida glabrata or Candida krusei). For hemodynamically unstable or neutropenic patients, agents with broader species coverage, such as polyenes, echinocandins, or, possibly, voriconazole, are preferred for empirical treatment of candidemia. Modification of the initial, empirical regimen depends on the response to therapy and the subsequent identification of the species of the offending pathogen. Echinocandins or high-dose polyenes are preferred for the treatment of infections with C. glabrata or C. krusei. Central venous catheters should be removed from all patients who have disseminated candidiasis, if feasible, and antifungal therapy should be administered to all patients who have candidemia or proven candidiasis. Candida organisms are opportunistic fungal pathogens that have become a major cause of nosocomial infections in the United States and worldwide. Candida species have become the third most common nosocomial bloodstream isolates and are exceeded in frequency only by coagulase-negative staphylococci and Staphylococcus aureus [1]. In the United States, the annual incidence of blood culture-confirmed candidemia reported in populationbased surveys is ∼10 cases/100,000 population [2, 3]. However, because blood cultures are insensitive for the diagnosis, up to half of the cases of disseminated candidiasis (defined as candidal infection in sterile target organs, with or without positive blood culture results) are never microbiologically confirmed. Therefore, estimates of disease frequency based on positive blood culture results are artificially low, and an annual incidence of у20 cases/ 100,000 population (у60,000 cases/year in the United States) is likely to be more accurate [4]. Although Candida species are opportunistic pathogens, the majority of patients who develop disseminated candidiasis are not immunosuppressed in the classical sense [5]. Rather, the predominant risk factors for disseminated candidiasis are common iatrogenic and/or nosocomial factors (table 1). Given the
When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oro... more When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invad...
Clinical Infectious Diseases, 2004
Candida species are the most common cause of fungal infections. Candida species produce infection... more Candida species are the most common cause of fungal infections. Candida species produce infections that range from non-life-threatening mucocutaneous illnesses to invasive processes that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. These guidelines summarize current knowledge about treatment of multiple forms of candidiasis for the Infectious Diseases Society of America (IDSA). Throughout this document, treatment recommendations are rated according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the supporting evidence and quality of the underlying data (table 1). This document covers the following 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. However, susceptibility testing of fungi is not considered a routine testing procedure in many laboratories, is not always promptly available, and is not universally considered as the standard of care. Knowledge of the infecting species, however, is highly predictive of likely susceptibility and can be used as a guide to therapy. The guidelines review the available infor
Clinical Infectious …
Featured in New York Times "Searching the Web for Flu Outbreaks" November 28, 2008 Usin... more Featured in New York Times "Searching the Web for Flu Outbreaks" November 28, 2008 Using Internet Searches for Influenza Surveillance Philip M. Polgreen, Yiling Chen, David M. Pennock, and Forrest D. Nelson One study, published by the journal Clinical Infectious ...
Chest, 2001
Because of the rapidly increasing incidence of serious candidal infections, a consensus conferenc... more Because of the rapidly increasing incidence of serious candidal infections, a consensus conference of 22 investigators from the United States, Europe, and Japan was held to discuss strategies for the prevention and treatment of deep-organ infections caused by Candida species. Commonly asked questions concerning the management of candidal infections were selected for discussion by the participating investigators. Possible answers to the questions were developed by the investigators, who then voted anonymously for their preferences. In certain instances, unanimity or a strong consensus was the result. In all cases, the full spectrum of responses was recorded and is presented in this report. The forms of candidal infection addressed included candidemia, candiduria, hepatosplenic candidiasis (chronic systemic candidiasis), candidal endophthalmitis, and candidal peritonitis. Prevention and treatment strategies were considered for patients who have undergone surgery, for neutropenic and nonneutropenic patients, and for patients who have undergone bone marrow and solid organ transplantation. The therapeutic roles of amphotericin B (standard and lipid formulations) and the azoles were considered.
New England Journal of Medicine, 2006
Eukaryotic Cell, 2002
Candida albicans is an important pathogen of immunocompromised patients which grows with true hyp... more Candida albicans is an important pathogen of immunocompromised patients which grows with true hyphal, pseudohyphal, and yeast morphologies. The dynamics of cell cycle progression are markedly different in true hyphal relative to pseudohyphal and yeast cells, including nuclear movement and septin ring positioning. In Saccharomyces cerevisiae, two forkhead transcription factors (ScFKH1 and ScFKH2) regulate the expression of B-cyclin genes. In
JAIDS Journal of Acquired Immune Deficiency Syndromes, 2002
The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was exami... more The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was examined in Adult AIDS Clinical Trial Group (AACTG) 722, a virology substudy of AACTG 323: a phase 4 randomized study designed to examine the use of chronic suppressive versus episodic fluconazole therapy. The primary analysis used a case-control sampling scheme with two controls per "case" (subjects that developed an OI) matched by gender, age, and time on study. Forty-five cases and matched controls were identified and used in the analysis. Study 722 accrued 518 subjects between 5/97 and 11/99. Forty-five subjects developed serious OIs or refractory candidiasis. Median baseline CD4 count was 24 cell/mm3 for cases and 46 for controls (p =.003). Median viral load (VL) was 5.02 log10 copies/mL for cases and 4.08 for controls (p =.002). Multivariate analysis found four independent variables associated with time to OI: baseline VL and CD4 (RR = 2.2 per log increment and 6.0 per 50-cell increment, respectively), a one log increase in VL at any time (RR = 15), and history of an OI (RR = 5.2). VL and changes in VL were independently associated with risk of development of OIs in a prospective study and should be considered by clinicians when assessing patients for risk of OI.