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$30 million NIA consortium explores links between vascular health and Alzheimer’s disease
BETHESDA, MD. – Cerebral vascular dysfunction exerts a significant negative influence on cognition, doubling the risk of dementia in old age and speeding the rate of cognitive decline.
These findings have been confirmed in a number of studies, and their advancement in both research and clinical arenas continues. But studies of the vascular conditions that affect cognition remain largely observational. Intervention trials are few and limited in scope. The dearth of animal models that express compromised cerebral vascular function has made conducting basic studies feel like wheels spinning in the mud.
According to investigators who discussed the problem at the recent Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health, the situation calls for a targeted push to better understand vascular complications and their impact on cognition and the development of dementias – and a new, 5-year NIH research program aims to do just that.
M²OVE–AD: Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease, is a $30 million initiative that brings together more than a dozen research teams. Investigators will employ new molecular profiling technologies and big data analytics to understand how vascular dysfunction influences the development of Alzheimer’s. The teams will collaborate on five different projects, each exploring a different facet of these complex processes, according to Dr. Suzana Petanceska, program director of the neuroscience division at the National Institute on Aging, Bethesda, Md., who shared her thoughts after the meeting.
“The central goal of the consortium is to generate a deeper understanding of the molecular mechanisms linking vascular risk factors, cerebrovascular disease, and Alzheimer’s, and to generate a new big-data resource that will aid the discovery of therapeutic targets for disease treatment and prevention and molecular signatures that can be used as biomarkers for disease risk,” Dr. Petanceska said in an interview.
Following a new trend of sharing Alzheimer’s research data across public and academic domains, data generated by this program will be made rapidly available to the greater research community. “Making these complex biological data sets available and usable by researchers other than the data generators is key to accelerating the pace at which the research community can generate new knowledge and replicate new findings. The M²OVE–AD initiative builds on the open-science approach established by the Accelerating Medicines Partnership – AD Programand Alzheimer’s Disease Neuroimaging Initiative (ADNI). By coordinating the experimental and analytical approaches the research teams will maximize the usability of the data generated on these projects.”
Five complementary projects comprise the consortium:
Integrative Translational Discovery of Vascular Risk Factors in Aging and Dementia
Researchers at the Mayo Clinics in Minnesota and Florida will collaborate with those at the Icahn Institute for Genomics and Multiscale Biology, New York, to explore how molecular networks influence vascular risk in normal aging, as well as in Alzheimer’s and other dementias.
The project’s goal is to understand how gender and the Alzheimer’s disease risk factor gene ApoE4 influence the molecular processes that lead to Alzheimer’s-related cerebral amyloid angiopathy (CAA).
CAA appears to be a key player in the progression of Alzheimer’s disease. The health of small vessels of the brain is important not only in age-related cognitive decline, but also in amyloid clearance. When amyloid collects in these vessels, it may cause a potentially self-sustaining loop of vascular injury and impaired amyloid clearance, which causes more intravascular amyloid deposition, more CAA, and increasing amyloid pathology.
The team intends to use genetic and expression profiling data from human brain and bloods samples, as well as existing molecular, clinical, and pathologic data in hopes of discovering therapeutic targets. The dynamic interaction between gender, apoE4 and aging and its impact on various AD pathologic and clinical traits will be explored in an array of existing and new animal models.
“Integrating the analysis of multidimensional human data with studies in animal models will accelerate the speed with which the findings can be translated to new interventions for treatment and prevention,” Dr. Petanceska said.
Type 2 diabetes mellitus and prediabetes metabolic abnormalities affect one-third of U.S. adults and the majority of persons aged 60 years and older. Diabetes is associated with a higher risk of the clinical manifestations of AD, including dementia and mild cognitive impairment. Hispanics in the United States have higher rates of diabetes, putting them at greater risk for developing Alzheimer’s. Investigators at Columbia University and SUNY Downstate Medical Center, both in New York, will examine the complex relationship between diabetes, cerebrovascular disease, and Alzheimer’s in a cohort of 200 middle-aged Hispanic participants, with either normal glucose metabolism, prediabetes, or type 2 diabetes; the subjects will be followed for 5 years with whole-brain magnetic resonance imaging and a variety of cognitive measures. The brain imaging will track AD-like functional and pathologic changes and vascular lesions.
In addition, the team will carry out molecular profiling of plasma samples collected in the same participants to identify metabolic and protein signatures that may predict clinical, pathologic, and physiologic outcomes related to Alzheimer’s and cerebrovascular disease.
In a companion study using mouse models with diabetes and Alzheimer’s pathology traits, the researchers will examine how the interaction between diabetes and Alzheimer’s pathology affects the structure and function of neural circuits important to learning and memory.
“This project is addressing two critical knowledge gaps,” Dr. Petanceska said. “The first is understanding the mechanisms by which dysregulated glucose metabolism impacts the onset and progression of pathologic changes in the course of the preclinical phase of Alzheimer’s disease; the second is understanding the molecular determinants of AD risk in Hispanics, a population with higher prevalence of diabetes and at greater risk for AD.”
The Role of Renin-Angiotensin-Endothelial Pathway in Alzheimer’s Disease
Researchers at Emory University, Atlanta, will focus on understanding the molecular mechanisms by which vascular dysfunction associated with high blood pressure affects the onset and progression of Alzheimer’s.
The research cohort comprises 160 subjects from the Emory Cardiovascular Biobank and Predictive Health Study– 80 with normal cognition and 80 with mild cognitive impairment – who will be followed for 2 years. Molecular data (genomic, epigenetic and metabolomic) combined with clinical data on the same subjects collected over 2 years, will be used to build a molecular network model of the interaction between vascular dysfunction and various Alzheimer’s disease traits.
Parallel studies in a rat model that uniquely exhibits human-like AD neuropathology will help uncover the temporal relationship between vascular dysfunction and AD and examine the potential of the molecular regulators of vascular function, such as the renin-angiotensin system, as therapeutic targets for AD. The goal is to characterize this pathway as a therapeutic target.
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer’s-Type Dementias
Teams at Duke University, Durham, N.C., and the University of Pennsylvania, Philadelphia, will carry out extensive profiling of plasma samples from 900 ADNI participants and from participants in the Duke University MURDOCK Memory and Cognitive Health Study in search for lipid metabolites that are associated with cardiovascular disease and cognitive change. These lipidomic profiles will be integrated with the vast array of clinical and other molecular data available for these participants to identify molecular signatures that may be used to differentiate among various risk-factor types of AD.
In addition, in a subset of subjects, the team will compare the lipidomic profiles between plasma and cerebrospinal fluid; this will enable the team to test hypotheses about the role of systemic vascular and metabolic factors on cognitive aging and AD.
Cerebral Amyloid Angiopathy and Mechanisms of Brain Amyloid Accumulation
Investigators at Massachusetts General Hospital, Boston, will investigate the molecular underpinnings of CAA and its impact on Alzheimer’s disease. Employing a mouse model and human subjects with CAA, the study will explore this cycle of progressive amyloid deposition and brain injury. The team’s approach combines noninvasive detection and analysis of human CAA, real-time measurement of vascular structure and physiology in living transgenic mouse models, and molecular analysis of gene expression in brain microvessels. Ultimately, the team hopes to identify candidate therapies with which could block it.
“This highly multidisciplinary investigation into how the vascular effects of amyloid at the molecular, single-blood vessel, and whole-brain levels influence the clinical disease promises to deliver new, well-characterized therapeutic targets for disease prevention,” Dr. Petanceska said.
She predicted that the wide-ranging projects of the M²OVE–AD consortium will bring invaluable understanding to an enormously important, but still unexplored, aspect of Alzheimer’s pathology.
“We hope that this large-scale team science effort will generate an in-depth understanding of how vascular and metabolic factors contribute to neurodegenerative changes that result in cognitive decline and dementia and that the data and knowledge generated by this program will be the basis for developing effective interventions for disease treatment and prevention.”
On Twitter @Alz_Gal
BETHESDA, MD. – Cerebral vascular dysfunction exerts a significant negative influence on cognition, doubling the risk of dementia in old age and speeding the rate of cognitive decline.
These findings have been confirmed in a number of studies, and their advancement in both research and clinical arenas continues. But studies of the vascular conditions that affect cognition remain largely observational. Intervention trials are few and limited in scope. The dearth of animal models that express compromised cerebral vascular function has made conducting basic studies feel like wheels spinning in the mud.
According to investigators who discussed the problem at the recent Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health, the situation calls for a targeted push to better understand vascular complications and their impact on cognition and the development of dementias – and a new, 5-year NIH research program aims to do just that.
M²OVE–AD: Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease, is a $30 million initiative that brings together more than a dozen research teams. Investigators will employ new molecular profiling technologies and big data analytics to understand how vascular dysfunction influences the development of Alzheimer’s. The teams will collaborate on five different projects, each exploring a different facet of these complex processes, according to Dr. Suzana Petanceska, program director of the neuroscience division at the National Institute on Aging, Bethesda, Md., who shared her thoughts after the meeting.
“The central goal of the consortium is to generate a deeper understanding of the molecular mechanisms linking vascular risk factors, cerebrovascular disease, and Alzheimer’s, and to generate a new big-data resource that will aid the discovery of therapeutic targets for disease treatment and prevention and molecular signatures that can be used as biomarkers for disease risk,” Dr. Petanceska said in an interview.
Following a new trend of sharing Alzheimer’s research data across public and academic domains, data generated by this program will be made rapidly available to the greater research community. “Making these complex biological data sets available and usable by researchers other than the data generators is key to accelerating the pace at which the research community can generate new knowledge and replicate new findings. The M²OVE–AD initiative builds on the open-science approach established by the Accelerating Medicines Partnership – AD Programand Alzheimer’s Disease Neuroimaging Initiative (ADNI). By coordinating the experimental and analytical approaches the research teams will maximize the usability of the data generated on these projects.”
Five complementary projects comprise the consortium:
Integrative Translational Discovery of Vascular Risk Factors in Aging and Dementia
Researchers at the Mayo Clinics in Minnesota and Florida will collaborate with those at the Icahn Institute for Genomics and Multiscale Biology, New York, to explore how molecular networks influence vascular risk in normal aging, as well as in Alzheimer’s and other dementias.
The project’s goal is to understand how gender and the Alzheimer’s disease risk factor gene ApoE4 influence the molecular processes that lead to Alzheimer’s-related cerebral amyloid angiopathy (CAA).
CAA appears to be a key player in the progression of Alzheimer’s disease. The health of small vessels of the brain is important not only in age-related cognitive decline, but also in amyloid clearance. When amyloid collects in these vessels, it may cause a potentially self-sustaining loop of vascular injury and impaired amyloid clearance, which causes more intravascular amyloid deposition, more CAA, and increasing amyloid pathology.
The team intends to use genetic and expression profiling data from human brain and bloods samples, as well as existing molecular, clinical, and pathologic data in hopes of discovering therapeutic targets. The dynamic interaction between gender, apoE4 and aging and its impact on various AD pathologic and clinical traits will be explored in an array of existing and new animal models.
“Integrating the analysis of multidimensional human data with studies in animal models will accelerate the speed with which the findings can be translated to new interventions for treatment and prevention,” Dr. Petanceska said.
Type 2 diabetes mellitus and prediabetes metabolic abnormalities affect one-third of U.S. adults and the majority of persons aged 60 years and older. Diabetes is associated with a higher risk of the clinical manifestations of AD, including dementia and mild cognitive impairment. Hispanics in the United States have higher rates of diabetes, putting them at greater risk for developing Alzheimer’s. Investigators at Columbia University and SUNY Downstate Medical Center, both in New York, will examine the complex relationship between diabetes, cerebrovascular disease, and Alzheimer’s in a cohort of 200 middle-aged Hispanic participants, with either normal glucose metabolism, prediabetes, or type 2 diabetes; the subjects will be followed for 5 years with whole-brain magnetic resonance imaging and a variety of cognitive measures. The brain imaging will track AD-like functional and pathologic changes and vascular lesions.
In addition, the team will carry out molecular profiling of plasma samples collected in the same participants to identify metabolic and protein signatures that may predict clinical, pathologic, and physiologic outcomes related to Alzheimer’s and cerebrovascular disease.
In a companion study using mouse models with diabetes and Alzheimer’s pathology traits, the researchers will examine how the interaction between diabetes and Alzheimer’s pathology affects the structure and function of neural circuits important to learning and memory.
“This project is addressing two critical knowledge gaps,” Dr. Petanceska said. “The first is understanding the mechanisms by which dysregulated glucose metabolism impacts the onset and progression of pathologic changes in the course of the preclinical phase of Alzheimer’s disease; the second is understanding the molecular determinants of AD risk in Hispanics, a population with higher prevalence of diabetes and at greater risk for AD.”
The Role of Renin-Angiotensin-Endothelial Pathway in Alzheimer’s Disease
Researchers at Emory University, Atlanta, will focus on understanding the molecular mechanisms by which vascular dysfunction associated with high blood pressure affects the onset and progression of Alzheimer’s.
The research cohort comprises 160 subjects from the Emory Cardiovascular Biobank and Predictive Health Study– 80 with normal cognition and 80 with mild cognitive impairment – who will be followed for 2 years. Molecular data (genomic, epigenetic and metabolomic) combined with clinical data on the same subjects collected over 2 years, will be used to build a molecular network model of the interaction between vascular dysfunction and various Alzheimer’s disease traits.
Parallel studies in a rat model that uniquely exhibits human-like AD neuropathology will help uncover the temporal relationship between vascular dysfunction and AD and examine the potential of the molecular regulators of vascular function, such as the renin-angiotensin system, as therapeutic targets for AD. The goal is to characterize this pathway as a therapeutic target.
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer’s-Type Dementias
Teams at Duke University, Durham, N.C., and the University of Pennsylvania, Philadelphia, will carry out extensive profiling of plasma samples from 900 ADNI participants and from participants in the Duke University MURDOCK Memory and Cognitive Health Study in search for lipid metabolites that are associated with cardiovascular disease and cognitive change. These lipidomic profiles will be integrated with the vast array of clinical and other molecular data available for these participants to identify molecular signatures that may be used to differentiate among various risk-factor types of AD.
In addition, in a subset of subjects, the team will compare the lipidomic profiles between plasma and cerebrospinal fluid; this will enable the team to test hypotheses about the role of systemic vascular and metabolic factors on cognitive aging and AD.
Cerebral Amyloid Angiopathy and Mechanisms of Brain Amyloid Accumulation
Investigators at Massachusetts General Hospital, Boston, will investigate the molecular underpinnings of CAA and its impact on Alzheimer’s disease. Employing a mouse model and human subjects with CAA, the study will explore this cycle of progressive amyloid deposition and brain injury. The team’s approach combines noninvasive detection and analysis of human CAA, real-time measurement of vascular structure and physiology in living transgenic mouse models, and molecular analysis of gene expression in brain microvessels. Ultimately, the team hopes to identify candidate therapies with which could block it.
“This highly multidisciplinary investigation into how the vascular effects of amyloid at the molecular, single-blood vessel, and whole-brain levels influence the clinical disease promises to deliver new, well-characterized therapeutic targets for disease prevention,” Dr. Petanceska said.
She predicted that the wide-ranging projects of the M²OVE–AD consortium will bring invaluable understanding to an enormously important, but still unexplored, aspect of Alzheimer’s pathology.
“We hope that this large-scale team science effort will generate an in-depth understanding of how vascular and metabolic factors contribute to neurodegenerative changes that result in cognitive decline and dementia and that the data and knowledge generated by this program will be the basis for developing effective interventions for disease treatment and prevention.”
On Twitter @Alz_Gal
BETHESDA, MD. – Cerebral vascular dysfunction exerts a significant negative influence on cognition, doubling the risk of dementia in old age and speeding the rate of cognitive decline.
These findings have been confirmed in a number of studies, and their advancement in both research and clinical arenas continues. But studies of the vascular conditions that affect cognition remain largely observational. Intervention trials are few and limited in scope. The dearth of animal models that express compromised cerebral vascular function has made conducting basic studies feel like wheels spinning in the mud.
According to investigators who discussed the problem at the recent Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health, the situation calls for a targeted push to better understand vascular complications and their impact on cognition and the development of dementias – and a new, 5-year NIH research program aims to do just that.
M²OVE–AD: Molecular Mechanisms of the Vascular Etiology of Alzheimer’s Disease, is a $30 million initiative that brings together more than a dozen research teams. Investigators will employ new molecular profiling technologies and big data analytics to understand how vascular dysfunction influences the development of Alzheimer’s. The teams will collaborate on five different projects, each exploring a different facet of these complex processes, according to Dr. Suzana Petanceska, program director of the neuroscience division at the National Institute on Aging, Bethesda, Md., who shared her thoughts after the meeting.
“The central goal of the consortium is to generate a deeper understanding of the molecular mechanisms linking vascular risk factors, cerebrovascular disease, and Alzheimer’s, and to generate a new big-data resource that will aid the discovery of therapeutic targets for disease treatment and prevention and molecular signatures that can be used as biomarkers for disease risk,” Dr. Petanceska said in an interview.
Following a new trend of sharing Alzheimer’s research data across public and academic domains, data generated by this program will be made rapidly available to the greater research community. “Making these complex biological data sets available and usable by researchers other than the data generators is key to accelerating the pace at which the research community can generate new knowledge and replicate new findings. The M²OVE–AD initiative builds on the open-science approach established by the Accelerating Medicines Partnership – AD Programand Alzheimer’s Disease Neuroimaging Initiative (ADNI). By coordinating the experimental and analytical approaches the research teams will maximize the usability of the data generated on these projects.”
Five complementary projects comprise the consortium:
Integrative Translational Discovery of Vascular Risk Factors in Aging and Dementia
Researchers at the Mayo Clinics in Minnesota and Florida will collaborate with those at the Icahn Institute for Genomics and Multiscale Biology, New York, to explore how molecular networks influence vascular risk in normal aging, as well as in Alzheimer’s and other dementias.
The project’s goal is to understand how gender and the Alzheimer’s disease risk factor gene ApoE4 influence the molecular processes that lead to Alzheimer’s-related cerebral amyloid angiopathy (CAA).
CAA appears to be a key player in the progression of Alzheimer’s disease. The health of small vessels of the brain is important not only in age-related cognitive decline, but also in amyloid clearance. When amyloid collects in these vessels, it may cause a potentially self-sustaining loop of vascular injury and impaired amyloid clearance, which causes more intravascular amyloid deposition, more CAA, and increasing amyloid pathology.
The team intends to use genetic and expression profiling data from human brain and bloods samples, as well as existing molecular, clinical, and pathologic data in hopes of discovering therapeutic targets. The dynamic interaction between gender, apoE4 and aging and its impact on various AD pathologic and clinical traits will be explored in an array of existing and new animal models.
“Integrating the analysis of multidimensional human data with studies in animal models will accelerate the speed with which the findings can be translated to new interventions for treatment and prevention,” Dr. Petanceska said.
Type 2 diabetes mellitus and prediabetes metabolic abnormalities affect one-third of U.S. adults and the majority of persons aged 60 years and older. Diabetes is associated with a higher risk of the clinical manifestations of AD, including dementia and mild cognitive impairment. Hispanics in the United States have higher rates of diabetes, putting them at greater risk for developing Alzheimer’s. Investigators at Columbia University and SUNY Downstate Medical Center, both in New York, will examine the complex relationship between diabetes, cerebrovascular disease, and Alzheimer’s in a cohort of 200 middle-aged Hispanic participants, with either normal glucose metabolism, prediabetes, or type 2 diabetes; the subjects will be followed for 5 years with whole-brain magnetic resonance imaging and a variety of cognitive measures. The brain imaging will track AD-like functional and pathologic changes and vascular lesions.
In addition, the team will carry out molecular profiling of plasma samples collected in the same participants to identify metabolic and protein signatures that may predict clinical, pathologic, and physiologic outcomes related to Alzheimer’s and cerebrovascular disease.
In a companion study using mouse models with diabetes and Alzheimer’s pathology traits, the researchers will examine how the interaction between diabetes and Alzheimer’s pathology affects the structure and function of neural circuits important to learning and memory.
“This project is addressing two critical knowledge gaps,” Dr. Petanceska said. “The first is understanding the mechanisms by which dysregulated glucose metabolism impacts the onset and progression of pathologic changes in the course of the preclinical phase of Alzheimer’s disease; the second is understanding the molecular determinants of AD risk in Hispanics, a population with higher prevalence of diabetes and at greater risk for AD.”
The Role of Renin-Angiotensin-Endothelial Pathway in Alzheimer’s Disease
Researchers at Emory University, Atlanta, will focus on understanding the molecular mechanisms by which vascular dysfunction associated with high blood pressure affects the onset and progression of Alzheimer’s.
The research cohort comprises 160 subjects from the Emory Cardiovascular Biobank and Predictive Health Study– 80 with normal cognition and 80 with mild cognitive impairment – who will be followed for 2 years. Molecular data (genomic, epigenetic and metabolomic) combined with clinical data on the same subjects collected over 2 years, will be used to build a molecular network model of the interaction between vascular dysfunction and various Alzheimer’s disease traits.
Parallel studies in a rat model that uniquely exhibits human-like AD neuropathology will help uncover the temporal relationship between vascular dysfunction and AD and examine the potential of the molecular regulators of vascular function, such as the renin-angiotensin system, as therapeutic targets for AD. The goal is to characterize this pathway as a therapeutic target.
Metabolic Signatures Underlying Vascular Risk Factors for Alzheimer’s-Type Dementias
Teams at Duke University, Durham, N.C., and the University of Pennsylvania, Philadelphia, will carry out extensive profiling of plasma samples from 900 ADNI participants and from participants in the Duke University MURDOCK Memory and Cognitive Health Study in search for lipid metabolites that are associated with cardiovascular disease and cognitive change. These lipidomic profiles will be integrated with the vast array of clinical and other molecular data available for these participants to identify molecular signatures that may be used to differentiate among various risk-factor types of AD.
In addition, in a subset of subjects, the team will compare the lipidomic profiles between plasma and cerebrospinal fluid; this will enable the team to test hypotheses about the role of systemic vascular and metabolic factors on cognitive aging and AD.
Cerebral Amyloid Angiopathy and Mechanisms of Brain Amyloid Accumulation
Investigators at Massachusetts General Hospital, Boston, will investigate the molecular underpinnings of CAA and its impact on Alzheimer’s disease. Employing a mouse model and human subjects with CAA, the study will explore this cycle of progressive amyloid deposition and brain injury. The team’s approach combines noninvasive detection and analysis of human CAA, real-time measurement of vascular structure and physiology in living transgenic mouse models, and molecular analysis of gene expression in brain microvessels. Ultimately, the team hopes to identify candidate therapies with which could block it.
“This highly multidisciplinary investigation into how the vascular effects of amyloid at the molecular, single-blood vessel, and whole-brain levels influence the clinical disease promises to deliver new, well-characterized therapeutic targets for disease prevention,” Dr. Petanceska said.
She predicted that the wide-ranging projects of the M²OVE–AD consortium will bring invaluable understanding to an enormously important, but still unexplored, aspect of Alzheimer’s pathology.
“We hope that this large-scale team science effort will generate an in-depth understanding of how vascular and metabolic factors contribute to neurodegenerative changes that result in cognitive decline and dementia and that the data and knowledge generated by this program will be the basis for developing effective interventions for disease treatment and prevention.”
On Twitter @Alz_Gal
AT ADRD 2016 SUMMIT
C. difficile infections raise risk of death, long-term care for seniors
AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.
A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.
His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.
Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.
C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.
“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.
Dr. Dubberke had no financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.
A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.
His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.
Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.
C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.
“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.
Dr. Dubberke had no financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – Clostridium difficile infections are a major driver of death and nursing home placement in Americans older than 65 years, according to research presented at a major international conference on infectious diseases.
A Medicare database review of almost 1.6 million patients has determined that 36% of those with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality. The infections also doubled the risk of placement in a skilled care nursing facility and tripled the risk of nursing home admission, Dr. Erik Dubberke said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Dr. Dubberke, an infectious disease specialist at Washington University, St. Louis, said these findings underscore not only the infection’s potential lethality, but its considerable impact on both short- and long-term quality of life.
His case-control study included 175,000 patients older than 65 years who were diagnosed with a C. difficile infection in 2011 – they were then matched with 1.45 million controls. This yielded 129,000 pairs matched for mortality, 105,000 matched for skilled nursing facility admission, and 93,500 matched for nursing home admission. The analysis controlled for age, gender, race, other infections, as well as health care utilization and a comprehensive group of acute and chronic conditions in the prior 12 months.
Overall, Dr. Dubberke found that 36% of cases and 25% of controls died during the year – a 44% increased risk of death and an 11% attributable mortality rate. During the same period, another 36% of the C. difficile cases were admitted to a skilled nursing facility, compared with 19% of controls – an 89% increased risk and 17% attributable admission rate.
C. difficile infections also exerted a significant impact on nursing home admissions: 15% of the cases in the study were admitted, compared with 5% of controls. This represented almost a tripling of risk (relative risk, 2.80), with an attributable admission rate of 10%, Dr. Dubberke said.
“These findings illustrate how C. difficile impacts quality of life, with short-term morbidity reflected in increasing admissions to skilled nursing facilities, and long-term morbidity by increasing admissions to nursing homes,” he said.
Dr. Dubberke had no financial disclosures.
On Twitter @Alz_Gal
AT ECCMID 2016
Key clinical point: Clostridium difficile infections are key drivers of death and long-term care placement among U.S. senior citizens.
Major finding: In 2011, 36% of older patients with C. difficile died, compared with 25% of an age-matched control group – an 11% attributable mortality.
Data source: A case-control study involving over 1.5 million Medicare recipients.
Disclosures: Dr. Dubberke had no financial disclosures.
Macrolide adds no benefit to pneumonia treatment in HIV patients
AMSTERDAM – Adding a macrolide to beta-lactam antibiotic treatment didn’t improve outcomes in HIV-infected patients with community-acquired bacterial pneumonia, according to the results of a Brazilian study.
Dr. Claudia Figueiredo Mello of the Instituto de Infectologia Emílio Ribas, São Paolo, said her study found no difference in in-hospital mortality between treatment with a beta-lactam alone, and treatment with the combination of a beta-lactam and a macrolide. Indeed, length of hospital stay was exactly the same. Dr. Mello reported the study results at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The study involved 228 patients with longstanding HIV infections and community-acquired bacterial pneumonia who were randomized to two treatment regimens. Protocol 1 was the standard treatment of 1 g ceftriaxone intravenously every 12 hours plus placebo for a minimum of 7 days. Protocol 2 was the same ceftriaxone treatment with the addition of azithromycin 500 mg/day or clarithromycin 500 mg every 12 hours.
Patients were a mean of 40 years old, with a median HIV duration of 12 years. Only about 20% were on regular highly active antiretroviral therapy (HAART); this was reflected in the low proportion of patients with a viral load of less than 50 copies/mL (about 16%), Dr. Mello said.
The median CD4 T-cell count varied widely in patients, but in half it was below 50 cells/mm3. Comorbidities were common in the cohort (30%); the most common were hypertension (12%) and liver disease (10%). Many patients used tobacco (41%), and illicit drug use was also common (about a third).
Most patients (60%) were risk class I-III on the Pneumonia Severity Index. Risk class III occurred in 20%, and the remainder were risk class IV and V.
In the intention-to-treat analysis, in-hospital mortality was 11% in the beta-lactam–only group and 15% in the combination therapy group – not a significant difference. The time to reach clinical stability was 5 days in each group, and the hospital length of stay, 14 days in each group.
Dr. Mello said she and her colleagues would continue to examine the data to determine if a specific subgroup might benefit from combination therapy, as extant data do suggest that adding a macrolide to beta-lactam treatment improves outcomes in a general population. She could not speculate as to why combination therapy didn’t appear to confer additional benefit on this cohort of patients living with HIV.
She had no financial disclosures.
AMSTERDAM – Adding a macrolide to beta-lactam antibiotic treatment didn’t improve outcomes in HIV-infected patients with community-acquired bacterial pneumonia, according to the results of a Brazilian study.
Dr. Claudia Figueiredo Mello of the Instituto de Infectologia Emílio Ribas, São Paolo, said her study found no difference in in-hospital mortality between treatment with a beta-lactam alone, and treatment with the combination of a beta-lactam and a macrolide. Indeed, length of hospital stay was exactly the same. Dr. Mello reported the study results at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The study involved 228 patients with longstanding HIV infections and community-acquired bacterial pneumonia who were randomized to two treatment regimens. Protocol 1 was the standard treatment of 1 g ceftriaxone intravenously every 12 hours plus placebo for a minimum of 7 days. Protocol 2 was the same ceftriaxone treatment with the addition of azithromycin 500 mg/day or clarithromycin 500 mg every 12 hours.
Patients were a mean of 40 years old, with a median HIV duration of 12 years. Only about 20% were on regular highly active antiretroviral therapy (HAART); this was reflected in the low proportion of patients with a viral load of less than 50 copies/mL (about 16%), Dr. Mello said.
The median CD4 T-cell count varied widely in patients, but in half it was below 50 cells/mm3. Comorbidities were common in the cohort (30%); the most common were hypertension (12%) and liver disease (10%). Many patients used tobacco (41%), and illicit drug use was also common (about a third).
Most patients (60%) were risk class I-III on the Pneumonia Severity Index. Risk class III occurred in 20%, and the remainder were risk class IV and V.
In the intention-to-treat analysis, in-hospital mortality was 11% in the beta-lactam–only group and 15% in the combination therapy group – not a significant difference. The time to reach clinical stability was 5 days in each group, and the hospital length of stay, 14 days in each group.
Dr. Mello said she and her colleagues would continue to examine the data to determine if a specific subgroup might benefit from combination therapy, as extant data do suggest that adding a macrolide to beta-lactam treatment improves outcomes in a general population. She could not speculate as to why combination therapy didn’t appear to confer additional benefit on this cohort of patients living with HIV.
She had no financial disclosures.
AMSTERDAM – Adding a macrolide to beta-lactam antibiotic treatment didn’t improve outcomes in HIV-infected patients with community-acquired bacterial pneumonia, according to the results of a Brazilian study.
Dr. Claudia Figueiredo Mello of the Instituto de Infectologia Emílio Ribas, São Paolo, said her study found no difference in in-hospital mortality between treatment with a beta-lactam alone, and treatment with the combination of a beta-lactam and a macrolide. Indeed, length of hospital stay was exactly the same. Dr. Mello reported the study results at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
The study involved 228 patients with longstanding HIV infections and community-acquired bacterial pneumonia who were randomized to two treatment regimens. Protocol 1 was the standard treatment of 1 g ceftriaxone intravenously every 12 hours plus placebo for a minimum of 7 days. Protocol 2 was the same ceftriaxone treatment with the addition of azithromycin 500 mg/day or clarithromycin 500 mg every 12 hours.
Patients were a mean of 40 years old, with a median HIV duration of 12 years. Only about 20% were on regular highly active antiretroviral therapy (HAART); this was reflected in the low proportion of patients with a viral load of less than 50 copies/mL (about 16%), Dr. Mello said.
The median CD4 T-cell count varied widely in patients, but in half it was below 50 cells/mm3. Comorbidities were common in the cohort (30%); the most common were hypertension (12%) and liver disease (10%). Many patients used tobacco (41%), and illicit drug use was also common (about a third).
Most patients (60%) were risk class I-III on the Pneumonia Severity Index. Risk class III occurred in 20%, and the remainder were risk class IV and V.
In the intention-to-treat analysis, in-hospital mortality was 11% in the beta-lactam–only group and 15% in the combination therapy group – not a significant difference. The time to reach clinical stability was 5 days in each group, and the hospital length of stay, 14 days in each group.
Dr. Mello said she and her colleagues would continue to examine the data to determine if a specific subgroup might benefit from combination therapy, as extant data do suggest that adding a macrolide to beta-lactam treatment improves outcomes in a general population. She could not speculate as to why combination therapy didn’t appear to confer additional benefit on this cohort of patients living with HIV.
She had no financial disclosures.
AT ECCMID 2016
Key clinical point: Adding a macrolide to beta-lactam antibiotic treatment didn’t improve outcomes in HIV-positive patients with community-acquired pneumonia.
Major finding: In-hospital mortality was 11% in the combination group and 15% in the beta-lactam–only group.
Data source: A randomized, controlled trial comprising 228 patients.
Disclosures: Dr. Mello had no financial obligations.
PPIs associated with antibiotic-resistant bacteria carriage
AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.
The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.
“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”
PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.
To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.
He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).
In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.
Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.
“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”
Dr. Huizinga had no relevant financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.
The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.
“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”
PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.
To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.
He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).
In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.
Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.
“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”
Dr. Huizinga had no relevant financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.
The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.
“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”
PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.
To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.
He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).
In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.
Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.
“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”
Dr. Huizinga had no relevant financial disclosures.
On Twitter @Alz_Gal
AT ECCMID 2016
Key clinical point: Proton pump inhibitors may increase the risk of carrying antibiotic-resistant bacteria.
Major finding: PPIs conferred a fourfold increase in the risk of being colonized with extended-spectrum beta-lactamase–producing enterobacteriaceae.
Data source: A cross-sectional study involving 570 patients.
Disclosures: Dr. Huizinga had no relevant financial disclosures.
VIDEO: Beyond amyloid, the complexity of Alzheimer’s deepens
BETHESDA, MD. – Dr. John Hardy first theorized the amyloid cascade hypothesis in 1992. Since then, amyloid-beta has remained the prime focus of Alzheimer’s disease research and therapy. But as the understanding of Alzheimer’s pathogenesis deepens, critical genetic and environmental interactions with amyloid become ever more important in untangling the disorder’s mysteries.
In this interview at the National Institutes of Health’s Alzheimer’s Disease–Related Dementias 2016 Summit, Dr. Hardy of University College London Institute of Neurology discusses some of the issues behind treating and studying clinical differences in Alzheimer’s disease and other types of dementia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
BETHESDA, MD. – Dr. John Hardy first theorized the amyloid cascade hypothesis in 1992. Since then, amyloid-beta has remained the prime focus of Alzheimer’s disease research and therapy. But as the understanding of Alzheimer’s pathogenesis deepens, critical genetic and environmental interactions with amyloid become ever more important in untangling the disorder’s mysteries.
In this interview at the National Institutes of Health’s Alzheimer’s Disease–Related Dementias 2016 Summit, Dr. Hardy of University College London Institute of Neurology discusses some of the issues behind treating and studying clinical differences in Alzheimer’s disease and other types of dementia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
BETHESDA, MD. – Dr. John Hardy first theorized the amyloid cascade hypothesis in 1992. Since then, amyloid-beta has remained the prime focus of Alzheimer’s disease research and therapy. But as the understanding of Alzheimer’s pathogenesis deepens, critical genetic and environmental interactions with amyloid become ever more important in untangling the disorder’s mysteries.
In this interview at the National Institutes of Health’s Alzheimer’s Disease–Related Dementias 2016 Summit, Dr. Hardy of University College London Institute of Neurology discusses some of the issues behind treating and studying clinical differences in Alzheimer’s disease and other types of dementia.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
EXPERT ANALYSIS FROM THE ADRD SUMMIT 2016
Standard incubation can miss P. acnes in infective endocarditis
AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.
But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.
“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”
Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.
All of the cases were confirmed by any of the following standards:
• Two or more blood cultures positive for P. acnes.
• Two or more valve cultures positive for P. acnes.
• Two or more valve sequencing rests positive for P. acnes.
• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.
Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.
The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.
The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).
The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.
The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.
Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.
All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.
Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.
Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).
In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.
Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.
The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.
There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.
The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.
“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”
She had no financial disclosures.
AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.
But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.
“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”
Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.
All of the cases were confirmed by any of the following standards:
• Two or more blood cultures positive for P. acnes.
• Two or more valve cultures positive for P. acnes.
• Two or more valve sequencing rests positive for P. acnes.
• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.
Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.
The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.
The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).
The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.
The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.
Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.
All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.
Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.
Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).
In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.
Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.
The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.
There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.
The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.
“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”
She had no financial disclosures.
AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.
But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.
“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”
Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.
All of the cases were confirmed by any of the following standards:
• Two or more blood cultures positive for P. acnes.
• Two or more valve cultures positive for P. acnes.
• Two or more valve sequencing rests positive for P. acnes.
• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.
Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.
The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.
The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).
The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.
The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.
Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.
All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.
Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.
Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).
In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.
Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.
The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.
There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.
The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.
“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”
She had no financial disclosures.
AT ECCMID 2016
Key clinical point: P. acnes’ slow growth may result in false negative blood cultures in infective endocarditis.
Major finding: Just 12% of blood cultures incubated for 5 days were positive, while 71% of those incubated for more than 5 days were positive.
Data source: The Cleveland Clinic Infective Endocarditis Registry.
Disclosures: Dr. Banzon had no financial disclosures.
Fecal transplant cures most with C. difficile, but one dies
AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.
However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.
The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.
They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.
Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.
The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.
The mean follow-up was 21 months, also with a wide range (3-68 months).
A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.
Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.
Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.
There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.
The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”
She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.
Of the other four patients with transplant complications:
• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.
• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.
• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.
• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.
During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.
• Colonoscopic administration is mandatory for any patient with a swallowing disorder.
• A smaller volume of feces is now infused.
• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.
• There is no eating or drinking for at least 1 hour after the transplant.
• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.
She had no financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.
However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.
The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.
They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.
Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.
The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.
The mean follow-up was 21 months, also with a wide range (3-68 months).
A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.
Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.
Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.
There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.
The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”
She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.
Of the other four patients with transplant complications:
• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.
• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.
• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.
• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.
During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.
• Colonoscopic administration is mandatory for any patient with a swallowing disorder.
• A smaller volume of feces is now infused.
• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.
• There is no eating or drinking for at least 1 hour after the transplant.
• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.
She had no financial disclosures.
On Twitter @Alz_Gal
AMSTERDAM – Fecal transplants effected a clinical cure in 97% of patients with recurrent Clostridium difficile infection, a small prospective study has determined.
However, the transplants, which were administered via duodenal intubation, were not without serious adverse events, Dr. Yvette van Beurden said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Five patients regurgitated or vomited fecal material, and one of these patients died, presumably from aspiration pneumonia related to the event, said Dr. van Beurden of the VU University Medical Center, Amsterdam.
The study was relatively small – 39 patients – but provided up to 2 years of follow-up on them. All were treated at Academic Medical Center, Amsterdam, from 2010 to 1016.
They were a mean of 73 years old, but the age range was wide (14-97 years). All had experienced recurrent C. difficile infections. The mean recurrence rate was four, but again this varied widely, from one recurrence to 10.
Thus, they had also experienced a mean of four courses of antibiotic treatment, with a range similar to the recurrence range. At the time of transplant, they were a mean of 6 months past their last recurrence.
The transplant protocol called for a minimum of 4 days of vancomycin treatment before transplant, and a full bowel prep 1 day before. The transplant itself consisted of 500 mL of fresh donor feces in solution; it was obtained from a household contact or healthy volunteer and administered by duodenal tube. Patients were discharged on the same day of infusion.
The mean follow-up was 21 months, also with a wide range (3-68 months).
A clinical cure – not microbiologically confirmed – occurred in 82% of the patients. There were seven recurrences (18%), which all happened within the first 3 months. Of these, two were thought to be related to antibiotic use within the first month of the procedure; the cause of the other recurrences was unknown.
Four of the patients with recurrent infections received antibiotics without a repeat transplant; three received fidaxomicin and one, metronidazole. Two underwent a successful repeat transplant. One patient had multiple treatments, including a course of fidaxomicin. This patient experienced another recurrence that was successfully treated with a second transplant.
Six of these seven patients experienced a clinical cure, bringing the secondary cure rate of the entire cohort to 97%.
There were nine serious adverse events (23%), most of which occurred during or shortly after the transplant procedure. This included the single death; four hospitalizations (one related to the transplant); and four transplant-related events.
The patient who died had an uncomplicated transplant, but within an hour started to feel nauseated and regurgitated the fecal material. “This didn’t appear to be severe,” Dr. van Beurden said. “But within a week, pneumonia developed and the patient died despite antibiotic treatment.”
She added that this patient was “medically fragile,” with a swallowing disorder that required a percutaneous endoscopic gastrostomy feeding tube.
Of the other four patients with transplant complications:
• One, following an uncomplicated transplant, was discharged and ate a large meal, then shortly after vomited food and donor feces.
• One experienced abdominal cramping during the procedure, which was immediately stopped. When the cramping subsided, the procedure was completed. However, within a few hours the cramping recurred, along with diarrhea, nausea, and vomiting of fecal material.
• One patient was “very stressed and anxious” during the procedure and regurgitated a mix of gastric juices and donor feces. The infusion tube was immediately removed. The patient was discharged after being symptom-free for 3 hours, but vomited fecal material on the way home.
• One patient experienced nausea during the transplant, which was immediately stopped with tube removal. Upon removal, the patient regurgitated donor material. Nausea shortly resolved.
During the discussion period, Dr. van Beurden fielded a question about duodenal administration rather than delivering the donor feces colonoscopically. She said that decision was made because the duodenal tube doesn’t require anesthesia, and because many of the patients had severely inflamed colons. However, the hospital’s experience with complications did help refine its transplant protocol, she said.
• Colonoscopic administration is mandatory for any patient with a swallowing disorder.
• A smaller volume of feces is now infused.
• Donor material is infused very slowly and immediately discontinued if there is any nausea, cramping, or regurgitation.
• There is no eating or drinking for at least 1 hour after the transplant.
• To minimize the risk of recurrent C. difficile, patients should have no nonessential antibiotic treatment within the first month after transplant.
She had no financial disclosures.
On Twitter @Alz_Gal
AT ECCMID 2016
Key clinical point: Fecal transplants cured most recurrent C. difficile infections, but could be dangerous as well.
Major finding: A duodenal administered fecal transplant cured 97% of patients with recurrent C. difficile, but one patient died after vomiting the fecal material.
Data source: The prospective study comprised 39 patients.
Disclosures: Dr. van Beurden had no financial disclosures.
Colombia reports first Zika deaths, all in medically compromised patients
AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.
All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).
Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.
“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”
Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.
From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.
The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.
All patients presented with anemia. All but the older man also had severe thrombocytopenia.
The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.
The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.
The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.
The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.
The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.
Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.
Dr. Rodriguez-Morales had no financial disclosures.
AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.
All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).
Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.
“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”
Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.
From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.
The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.
All patients presented with anemia. All but the older man also had severe thrombocytopenia.
The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.
The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.
The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.
The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.
The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.
Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.
Dr. Rodriguez-Morales had no financial disclosures.
AMSTERDAM – Five people with confirmed Zika virus infections have died in Colombia, and all had medical comorbidities, including leukemia, diabetes, sickle cell anemia, and hypertension.
All of the deaths occurred last October in northern and central Colombia, Dr. Alfonso Rodriguez-Morales said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
Four of the cases were simultaneously published April 7 in the Lancet Infectious Diseases (2016 Apr 7. doi: 10.1016/S1473-3099[16]30006-8). The fifth case occurred in northern Colombia, and was reported in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151934).
Reports of confirmed Zika-related deaths are rare. Brazil, the only other country to disclose them, has now reported three, said Dr. Rodriguez-Morales of the Universidad Tecnológica de Pereira, Colombia.
“Before the current outbreak in Latin America, Zika virus was not linked to deaths,” he noted. But the eight confirmed Zika-related deaths in South America “call attention to the need for evidence-based guidelines for clinical management of Zika, as well as the possible occurrence of atypical and severe cases, including possibly congenitally related microcephaly.”
Because they all occurred in medically compromised patients, Dr. Rodriguez-Morales also urged clinicians to cast a wary eye on such patients who present with arbovirus-type symptoms, including fever and rash.
From September 2015 to March 2016, Colombia had 58,838 reported cases of Zika. Of those, only 2,361 were lab confirmed. The rest were either diagnosed clinically or were suspected cases, Dr. Rodriguez-Morales said. Although Colombia has a much smaller population than Brazil (49 million vs. 210 million), its Zika case rate is much higher, 120 cases per 100,000 people vs. 34 cases per 100,000 people.
The group of four deaths occurred in central Colombia, and included a 2-year-old girl, a 30-year-old woman, a 61-year-old man, and a 72-year-old woman. All presented with 2-6 days of fever. All were initially suspected to have dengue fever or chikungunya. None tested positive for dengue, but the man was coinfected with chikungunya.
All patients presented with anemia. All but the older man also had severe thrombocytopenia.
The toddler presented with hepatomegaly, mucosal hemorrhage, progressive respiratory collapse, progressive thrombocytopenia, and intravascular coagulation. She died 5 days after symptom onset and was found to have had unrecognized lymphoblastic leukemia.
The 30-year-old woman presented with a severe rash on both arms. She also exhibited coagulation dysfunction, including severe thrombocytopenia and leukopenia that progressed to intracerebral and subarachnoid hemorrhage. She died 12 days after symptom onset. She was determined to have had unrecognized acute myeloid leukemia.
The elderly man had a history of medically controlled hypertension. He experienced mucosal hemorrhage and respiratory distress. He died 7 days after symptom onset. On autopsy, his liver showed necrotic areas, and his spleen indicated a systemic inflammatory response.
The elderly woman had a history of insulin-controlled type 2 diabetes. Her symptoms included gastrointestinal distress, thrombocytopenia, and acute respiratory failure. She died 48 hours after symptom onset; her brain showed edema and ischemic lesions.
The 15-year-old girl in northern Colombia had a 5-year history of sickle cell disease, which, Dr. Rodriguez-Morales pointed out, is a risk factor for arbovirus diseases. However, the patient had never been hospitalized for a vasoocclusive crisis. She presented with a high fever; joint, muscle, and abdominal pain; and jaundice. She was assumed to have dengue virus. Within another day, she had progressed into respiratory failure and was on a ventilator. She died less than 2 days later.
Her autopsy showed hepatic necrosis and severe decrease of splenic lymphoid tissue with splenic sequestration. Systemic inflammation probably triggered a fatal vasoocclusive crisis and splenic sequestration.
Dr. Rodriguez-Morales had no financial disclosures.
AT ECCMID 2016
VIDEO: Unraveling Alzheimer’s pathogenesis while testing lifestyle interventions
BETHESDA, MD. – Alzheimer’s disease is not the failure of a single type of cell – or even a single physiologic system, so while the search for effective treatments goes on, basic research must continue to unravel many of its fundamental mechanisms, according to Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, Minn.
But in lieu of available treatments that target the underlying pathology of Alzheimer’s, trials must continue to test lifestyle interventions with diet and exercise that in preliminary studies have started proving their worth in decreasing the risk of cognitive decline or delaying its onset.
Dr. Petersen discussed these issues in an interview at the Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
BETHESDA, MD. – Alzheimer’s disease is not the failure of a single type of cell – or even a single physiologic system, so while the search for effective treatments goes on, basic research must continue to unravel many of its fundamental mechanisms, according to Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, Minn.
But in lieu of available treatments that target the underlying pathology of Alzheimer’s, trials must continue to test lifestyle interventions with diet and exercise that in preliminary studies have started proving their worth in decreasing the risk of cognitive decline or delaying its onset.
Dr. Petersen discussed these issues in an interview at the Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
BETHESDA, MD. – Alzheimer’s disease is not the failure of a single type of cell – or even a single physiologic system, so while the search for effective treatments goes on, basic research must continue to unravel many of its fundamental mechanisms, according to Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center in Rochester, Minn.
But in lieu of available treatments that target the underlying pathology of Alzheimer’s, trials must continue to test lifestyle interventions with diet and exercise that in preliminary studies have started proving their worth in decreasing the risk of cognitive decline or delaying its onset.
Dr. Petersen discussed these issues in an interview at the Alzheimer’s Disease–Related Dementias 2016 Summit, sponsored by the National Institutes of Health.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @alz_gal
EXPERT ANALYSIS FROM THE ADRD SUMMIT 2016
Risk for IBD Doubled in Hidradenitis Suppurativa
WASHINGTON – Patients with hidradenitis suppurativa (HS) face an increased risk of also developing inflammatory bowel disease (IBD), Ahuva Cices said at the annual meeting of the American Academy of Dermatology.
In a case-control study, Ms. Cices found that those with a new diagnosis of HS were twice as likely as controls to also be diagnosed with inflammatory bowel disease, either concurrently or shortly afterward.
“Our findings support a comorbid relationship between these two disorders, and suggest that hidradenitis suppurativa should be considered a risk factor for IBD and impart increased clinical suspicion for undiagnosed IBD,” said Ms. Cices of Northwestern University, Chicago.
She and her coinvestigators at Northwestern searched a large academic medical center database for patients with a diagnosis of HS from 2005 to 2015. These 1,332 patients were matched with about 2,600 control subjects. Of the individuals with HS, 20 were also concurrently or subsequently diagnosed with IBD. The mean lag time to an IBD diagnosis was 9 months.
The mean age of the patients with both conditions was almost 40 years. Most (75%) were female – significantly more than in the control group (42%). About half of the patients (45%) were black – also significantly more than in the control group (10%).
In a multivariate analysis, a diagnosis of HS conferred a doubling in the risk of a concurrent or subsequent diagnosis of IBD (odds ratio, 2.11), which was statistically significant.
The pathophysiologic link between the two diseases has been theorized but not confirmed, Ms. Cices said.
“The multifactorial pathways of HS and IBD are complicated, but they both involve inflammatory responses to normal flora, immune dysfunction, and dysregulation of Notch, the sulfotransferase enzyme, [tumor necrosis factor–]alpha, and T-helper 17 cells.”
She had no relevant financial disclosures.
WASHINGTON – Patients with hidradenitis suppurativa (HS) face an increased risk of also developing inflammatory bowel disease (IBD), Ahuva Cices said at the annual meeting of the American Academy of Dermatology.
In a case-control study, Ms. Cices found that those with a new diagnosis of HS were twice as likely as controls to also be diagnosed with inflammatory bowel disease, either concurrently or shortly afterward.
“Our findings support a comorbid relationship between these two disorders, and suggest that hidradenitis suppurativa should be considered a risk factor for IBD and impart increased clinical suspicion for undiagnosed IBD,” said Ms. Cices of Northwestern University, Chicago.
She and her coinvestigators at Northwestern searched a large academic medical center database for patients with a diagnosis of HS from 2005 to 2015. These 1,332 patients were matched with about 2,600 control subjects. Of the individuals with HS, 20 were also concurrently or subsequently diagnosed with IBD. The mean lag time to an IBD diagnosis was 9 months.
The mean age of the patients with both conditions was almost 40 years. Most (75%) were female – significantly more than in the control group (42%). About half of the patients (45%) were black – also significantly more than in the control group (10%).
In a multivariate analysis, a diagnosis of HS conferred a doubling in the risk of a concurrent or subsequent diagnosis of IBD (odds ratio, 2.11), which was statistically significant.
The pathophysiologic link between the two diseases has been theorized but not confirmed, Ms. Cices said.
“The multifactorial pathways of HS and IBD are complicated, but they both involve inflammatory responses to normal flora, immune dysfunction, and dysregulation of Notch, the sulfotransferase enzyme, [tumor necrosis factor–]alpha, and T-helper 17 cells.”
She had no relevant financial disclosures.
WASHINGTON – Patients with hidradenitis suppurativa (HS) face an increased risk of also developing inflammatory bowel disease (IBD), Ahuva Cices said at the annual meeting of the American Academy of Dermatology.
In a case-control study, Ms. Cices found that those with a new diagnosis of HS were twice as likely as controls to also be diagnosed with inflammatory bowel disease, either concurrently or shortly afterward.
“Our findings support a comorbid relationship between these two disorders, and suggest that hidradenitis suppurativa should be considered a risk factor for IBD and impart increased clinical suspicion for undiagnosed IBD,” said Ms. Cices of Northwestern University, Chicago.
She and her coinvestigators at Northwestern searched a large academic medical center database for patients with a diagnosis of HS from 2005 to 2015. These 1,332 patients were matched with about 2,600 control subjects. Of the individuals with HS, 20 were also concurrently or subsequently diagnosed with IBD. The mean lag time to an IBD diagnosis was 9 months.
The mean age of the patients with both conditions was almost 40 years. Most (75%) were female – significantly more than in the control group (42%). About half of the patients (45%) were black – also significantly more than in the control group (10%).
In a multivariate analysis, a diagnosis of HS conferred a doubling in the risk of a concurrent or subsequent diagnosis of IBD (odds ratio, 2.11), which was statistically significant.
The pathophysiologic link between the two diseases has been theorized but not confirmed, Ms. Cices said.
“The multifactorial pathways of HS and IBD are complicated, but they both involve inflammatory responses to normal flora, immune dysfunction, and dysregulation of Notch, the sulfotransferase enzyme, [tumor necrosis factor–]alpha, and T-helper 17 cells.”
She had no relevant financial disclosures.
AT AAD 16