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J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12. Published in final edited form as: J Invasive Fungal Infect. 2009 ; 2(4): 151–154.
Report from the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Infectious Diseases Society of America Joint Conference 2008: Washington, DC, USA, October 25–28, 2008
Author Manuscript
Shruti Gohil, MD, MPH and Liise-anne Pirofski, MD Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA The 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/46th Infectious Diseases Society of America (IDSA) 2008 joint conference program included presentations on many important topics in medical mycology. This meeting report briefly highlights selected abstracts, with an emphasis on those pertaining to the diagnosis and management of invasive fungal diseases.
Diagnostics
Author Manuscript
Despite advances in antifungal drug development, crude mortality rates attributable to invasive candidiasis (IC) have been relatively stagnant for nearly two decades [1]. Improvements in primary prophylaxis have contributed to a recent slight decline in the overall incidence of invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) patients; however, overall mortality remains unacceptably high, with reported case fatality rates as high as 60–85% [2]. A delay in diagnosis is a critical hurdle in effective management. Invasive candidiasis
Author Manuscript
Anna Lau (University of Sydney, Sydney, NSW, Australia) and colleagues presented an abstract on the use of multiplex-tandem polymerase chain reaction (MT-PCR) for the rapid detection of fungemia [3]. The assay was designed to identify up to 12 fungi (including seven Candida spp., Cryptococcus neoformans, Scedosporium spp., and Fusarium spp.; Aspergillus spp. were not included). The PCR assay was tested on 65 blood samples from 43 patients who also had blood cultures. The turnaround time was 1 μg/mL. However, overall MIC 50/90 increased from 0.25/0.5 μg/mL in 2000– 2002 to 0.5/1.0 μg/mL during 2005–2007, suggesting a slow trend towards increasing MICs since the use of voriconazole in IA became widespread [13]. Given the concerns regarding voriconazole hepatotoxicity, particularly in allogeneic HSCT patients, caspofungin has been studied as first-line treatment against IA in this subpopulation. In a study by Raoul Herbrecht and colleagues (Hôpital de Hautepierre, Strasbourg, France), patients with probable and proven IA were evaluated for a complete or partial response (CR and PR, respectively), which served as primary endpoints [14]. Secondary endpoints included response to treatment at day 84, survival, and safety. Among
J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12.
Gohil and Pirofski
Page 4
Author Manuscript
the 24 patients who met inclusion criteria, the median duration of caspofungin treatment was 24 days. A CR or PR was seen in 42% of patients by the end of treatment. However, it is noteworthy that 50% of patients had worsening disease. At day 84, the survival rate was 48%. No significant adverse drug reactions were reported. This study suggests that caspofungin is a viable first-line therapy for Aspergillus spp. in HSCT patients in whom voriconazole may convey a higher risk of hepatic toxicity [14].
Update on cryptococcosis
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Data were presented showing that cryptococcosis remains a medical mycosis of major importance. Benjamin J Park (Centers for Disease Control and Prevention [CDC], Atlanta, GA, USA) presented findings from a compelling CDC study, which estimated that the annual global burden of C neoformans meningitis among HIV patients is 957 900 cases, with a resultant number of deaths at 3 months of 624 700. The highest incidence was in SubSaharan Africa, followed by South/Southeast Asia (with estimated median incidences of 720 000 and 120 000 cases, respectively). Remarkably, these estimates surpass annual mortality rates from HIV-associated tuberculosis, underscoring the importance of improved diagnosis, prophylaxis/prevention, and treatment of cryptococcal disease in resource-poor settings [15].
Author Manuscript
In the same session, Brian Metzger (Albert Einstein College of Medicine) presented findings from a study linking the risk of cryptococcal disease among two separate cohorts of HIV patients with immunoglobulin M (IgM) memory B cell deficiency [16]. Remarkably, having less than 38% IgM memory B cells was significantly predictive of developing cryptococcal disease as much as 3 years prior to disease onset (odds ratio 12). This novel finding could allow identification of at-risk HIV patients who may benefit from early fungal prophylaxis determined not only by CD4+ T cell counts but also IgM memory B cell quantity, thereby potentially curbing the rising mortality of cryptococcal disease in HIV patients. Although the incidence of HIV-associated cryptococcosis in the US has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART), Cryptococcus-associated morbidity is a growing concern in immunocompetent hosts. Surveillance data from a Cryptococcus neoformans var. gattii outbreak in the Pacific Northwest revealed that all 11 cases studied occurred in HIV-negative patients; six of these patients had underlying comorbidities that required steroid use within 1 year of diagnosis [17], one had immunoglobulin G2 (IgG2) deficiency, and the remainder had no discernible immune compromise.
The role of fungus in chronic respiratory disease Author Manuscript
David Goldman (Albert Einstein College of Medicine) presented a series of studies outlining serological evidence of subclinical C neoformans among children residing in an urban setting, demonstrating hyper-reactive, allergic airway inflammation caused by non-lethal pulmonary infection with Cryptococcus in a murine model, and examining the unique abilities of this fungus to induce chitinase expression, which is increasingly being recognized as an important mediator of allergic pulmonary inflammation and hyperactivity [18]. These findings provide compelling evidence for a potential link between pulmonary cryptococcal infection and urban asthma in pediatric patients. Fungal colonization has been J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12.
Gohil and Pirofski
Page 5
Author Manuscript
correlated with severe, persistent asthma. David Denning (University of Manchester, Manchester, UK) presented findings from a randomized controlled trial of oral itraconazole treatment (200 mg orally twice daily) versus placebo for 32 weeks in patients with severe asthma with fungal sensitization. Patients with severe asthma who were sensitive to one or more of seven fungi by skin prick test had baseline IgE concentrations of
J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12. Published in final edited form as: J Invasive Fungal Infect. 2009 ; 2(4): 151–154.
Report from the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy and 46th Infectious Diseases Society of America Joint Conference 2008: Washington, DC, USA, October 25–28, 2008
Author Manuscript
Shruti Gohil, MD, MPH and Liise-anne Pirofski, MD Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY, USA The 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)/46th Infectious Diseases Society of America (IDSA) 2008 joint conference program included presentations on many important topics in medical mycology. This meeting report briefly highlights selected abstracts, with an emphasis on those pertaining to the diagnosis and management of invasive fungal diseases.
Diagnostics
Author Manuscript
Despite advances in antifungal drug development, crude mortality rates attributable to invasive candidiasis (IC) have been relatively stagnant for nearly two decades [1]. Improvements in primary prophylaxis have contributed to a recent slight decline in the overall incidence of invasive aspergillosis (IA) in hematopoietic stem cell transplant (HSCT) patients; however, overall mortality remains unacceptably high, with reported case fatality rates as high as 60–85% [2]. A delay in diagnosis is a critical hurdle in effective management. Invasive candidiasis
Author Manuscript
Anna Lau (University of Sydney, Sydney, NSW, Australia) and colleagues presented an abstract on the use of multiplex-tandem polymerase chain reaction (MT-PCR) for the rapid detection of fungemia [3]. The assay was designed to identify up to 12 fungi (including seven Candida spp., Cryptococcus neoformans, Scedosporium spp., and Fusarium spp.; Aspergillus spp. were not included). The PCR assay was tested on 65 blood samples from 43 patients who also had blood cultures. The turnaround time was 1 μg/mL. However, overall MIC 50/90 increased from 0.25/0.5 μg/mL in 2000– 2002 to 0.5/1.0 μg/mL during 2005–2007, suggesting a slow trend towards increasing MICs since the use of voriconazole in IA became widespread [13]. Given the concerns regarding voriconazole hepatotoxicity, particularly in allogeneic HSCT patients, caspofungin has been studied as first-line treatment against IA in this subpopulation. In a study by Raoul Herbrecht and colleagues (Hôpital de Hautepierre, Strasbourg, France), patients with probable and proven IA were evaluated for a complete or partial response (CR and PR, respectively), which served as primary endpoints [14]. Secondary endpoints included response to treatment at day 84, survival, and safety. Among
J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12.
Gohil and Pirofski
Page 4
Author Manuscript
the 24 patients who met inclusion criteria, the median duration of caspofungin treatment was 24 days. A CR or PR was seen in 42% of patients by the end of treatment. However, it is noteworthy that 50% of patients had worsening disease. At day 84, the survival rate was 48%. No significant adverse drug reactions were reported. This study suggests that caspofungin is a viable first-line therapy for Aspergillus spp. in HSCT patients in whom voriconazole may convey a higher risk of hepatic toxicity [14].
Update on cryptococcosis
Author Manuscript
Data were presented showing that cryptococcosis remains a medical mycosis of major importance. Benjamin J Park (Centers for Disease Control and Prevention [CDC], Atlanta, GA, USA) presented findings from a compelling CDC study, which estimated that the annual global burden of C neoformans meningitis among HIV patients is 957 900 cases, with a resultant number of deaths at 3 months of 624 700. The highest incidence was in SubSaharan Africa, followed by South/Southeast Asia (with estimated median incidences of 720 000 and 120 000 cases, respectively). Remarkably, these estimates surpass annual mortality rates from HIV-associated tuberculosis, underscoring the importance of improved diagnosis, prophylaxis/prevention, and treatment of cryptococcal disease in resource-poor settings [15].
Author Manuscript
In the same session, Brian Metzger (Albert Einstein College of Medicine) presented findings from a study linking the risk of cryptococcal disease among two separate cohorts of HIV patients with immunoglobulin M (IgM) memory B cell deficiency [16]. Remarkably, having less than 38% IgM memory B cells was significantly predictive of developing cryptococcal disease as much as 3 years prior to disease onset (odds ratio 12). This novel finding could allow identification of at-risk HIV patients who may benefit from early fungal prophylaxis determined not only by CD4+ T cell counts but also IgM memory B cell quantity, thereby potentially curbing the rising mortality of cryptococcal disease in HIV patients. Although the incidence of HIV-associated cryptococcosis in the US has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART), Cryptococcus-associated morbidity is a growing concern in immunocompetent hosts. Surveillance data from a Cryptococcus neoformans var. gattii outbreak in the Pacific Northwest revealed that all 11 cases studied occurred in HIV-negative patients; six of these patients had underlying comorbidities that required steroid use within 1 year of diagnosis [17], one had immunoglobulin G2 (IgG2) deficiency, and the remainder had no discernible immune compromise.
The role of fungus in chronic respiratory disease Author Manuscript
David Goldman (Albert Einstein College of Medicine) presented a series of studies outlining serological evidence of subclinical C neoformans among children residing in an urban setting, demonstrating hyper-reactive, allergic airway inflammation caused by non-lethal pulmonary infection with Cryptococcus in a murine model, and examining the unique abilities of this fungus to induce chitinase expression, which is increasingly being recognized as an important mediator of allergic pulmonary inflammation and hyperactivity [18]. These findings provide compelling evidence for a potential link between pulmonary cryptococcal infection and urban asthma in pediatric patients. Fungal colonization has been J Invasive Fungal Infect. Author manuscript; available in PMC 2016 April 12.
Gohil and Pirofski
Page 5
Author Manuscript
correlated with severe, persistent asthma. David Denning (University of Manchester, Manchester, UK) presented findings from a randomized controlled trial of oral itraconazole treatment (200 mg orally twice daily) versus placebo for 32 weeks in patients with severe asthma with fungal sensitization. Patients with severe asthma who were sensitive to one or more of seven fungi by skin prick test had baseline IgE concentrations of
