TBD Meeting (3205-19)

WASHINGTON – Although severe, community-acquired sepsis in previously healthy U.S. adults is relatively uncommon, it occurs often enough to strike about 40,000 people annually, and when previously healthy people are hospitalized for severe sepsis, their rate of in-hospital mortality was double the rate in people with one or more comorbidities who have severe, community-acquired sepsis, based on a review of almost 7 million Americans hospitalized for sepsis.

The findings “underscore the importance of improving public awareness of sepsis and emphasizing early sepsis recognition and treatment in all patients,” including those without comorbidities, Chanu Rhee, MD, said at an annual scientific meeting on infectious diseases. He hypothesized that the increased sepsis mortality among previously healthy patients may have stemmed from factors such as delayed sepsis recognition resulting in hospitalization at a more advanced stage and less aggressive management.

In addition, “the findings provide context for high-profile reports about sepsis death in previously healthy people,” said Dr. Rhee, an infectious diseases and critical care physician at Brigham and Women’s Hospital in Boston. Dr. Rhee and associates found that, among patients hospitalized with what the researchers defined as “community-acquired” sepsis, 3% were judged previously healthy by having no identified major or minor comorbidity or pregnancy at the time of hospitalization, a percentage that – while small – still translates into roughly 40,000 such cases annually in the United States. That helps explain why every so often a headline appears about a famous person who died suddenly and unexpectedly from sepsis, he noted.

The study used data collected on hospitalized U.S. patients in the Cerner Health Facts, HCA Healthcare, and Institute for Health Metrics and Evaluation databases, which included about 6.7 million people total including 337,983 identified as having community-acquired sepsis, defined as patients who met the criteria for adult sepsis advanced by the Centers for Disease Control and Prevention within 2 days of their hospital admission. The researchers looked further into the hospital records of these patients and divided them into patients with one or more major comorbidities (96% of the cohort), patients who were pregnant or had a “minor” comorbidity such as a lipid disorder, benign neoplasm, or obesity (1% of the study group), or those with no chronic comorbidity (3%; the subgroup the researchers deemed previously healthy).

In a multivariate analysis that adjusted for patients’ age, sex, race, infection site, and illness severity at the time of hospital admission the researchers found that the rate of in-hospital death among the previously healthy patients was exactly twice the rate of those who had at least one major chronic comorbidity, Dr. Rhee reported. Differences in the treatment received by the previously-healthy patients or in their medical status compared with patients with a major comorbidity suggested that the previously health patients were sicker. They had a higher rate of mechanical ventilation, 30%, compared with about 18% for those with a comorbidity; a higher rate of acute kidney injury, about 43% in those previously healthy and 28% in those with a comorbidity; and a higher percentage had an elevated lactate level, about 41% among the previously healthy patients and about 22% among those with a comorbidity.

[email protected]

SOURCE: Alrawashdeh M et al. Open Forum Infect Dis. 2019 Oct 23;6. Abstract 891.

WASHINGTON – Although severe, community-acquired sepsis in previously healthy U.S. adults is relatively uncommon, it occurs often enough to strike about 40,000 people annually, and when previously healthy people are hospitalized for severe sepsis, their rate of in-hospital mortality was double the rate in people with one or more comorbidities who have severe, community-acquired sepsis, based on a review of almost 7 million Americans hospitalized for sepsis.

The findings “underscore the importance of improving public awareness of sepsis and emphasizing early sepsis recognition and treatment in all patients,” including those without comorbidities, Chanu Rhee, MD, said at an annual scientific meeting on infectious diseases. He hypothesized that the increased sepsis mortality among previously healthy patients may have stemmed from factors such as delayed sepsis recognition resulting in hospitalization at a more advanced stage and less aggressive management.

In addition, “the findings provide context for high-profile reports about sepsis death in previously healthy people,” said Dr. Rhee, an infectious diseases and critical care physician at Brigham and Women’s Hospital in Boston. Dr. Rhee and associates found that, among patients hospitalized with what the researchers defined as “community-acquired” sepsis, 3% were judged previously healthy by having no identified major or minor comorbidity or pregnancy at the time of hospitalization, a percentage that – while small – still translates into roughly 40,000 such cases annually in the United States. That helps explain why every so often a headline appears about a famous person who died suddenly and unexpectedly from sepsis, he noted.

The study used data collected on hospitalized U.S. patients in the Cerner Health Facts, HCA Healthcare, and Institute for Health Metrics and Evaluation databases, which included about 6.7 million people total including 337,983 identified as having community-acquired sepsis, defined as patients who met the criteria for adult sepsis advanced by the Centers for Disease Control and Prevention within 2 days of their hospital admission. The researchers looked further into the hospital records of these patients and divided them into patients with one or more major comorbidities (96% of the cohort), patients who were pregnant or had a “minor” comorbidity such as a lipid disorder, benign neoplasm, or obesity (1% of the study group), or those with no chronic comorbidity (3%; the subgroup the researchers deemed previously healthy).

In a multivariate analysis that adjusted for patients’ age, sex, race, infection site, and illness severity at the time of hospital admission the researchers found that the rate of in-hospital death among the previously healthy patients was exactly twice the rate of those who had at least one major chronic comorbidity, Dr. Rhee reported. Differences in the treatment received by the previously-healthy patients or in their medical status compared with patients with a major comorbidity suggested that the previously health patients were sicker. They had a higher rate of mechanical ventilation, 30%, compared with about 18% for those with a comorbidity; a higher rate of acute kidney injury, about 43% in those previously healthy and 28% in those with a comorbidity; and a higher percentage had an elevated lactate level, about 41% among the previously healthy patients and about 22% among those with a comorbidity.

[email protected]

SOURCE: Alrawashdeh M et al. Open Forum Infect Dis. 2019 Oct 23;6. Abstract 891.

WASHINGTON – Although severe, community-acquired sepsis in previously healthy U.S. adults is relatively uncommon, it occurs often enough to strike about 40,000 people annually, and when previously healthy people are hospitalized for severe sepsis, their rate of in-hospital mortality was double the rate in people with one or more comorbidities who have severe, community-acquired sepsis, based on a review of almost 7 million Americans hospitalized for sepsis.

The findings “underscore the importance of improving public awareness of sepsis and emphasizing early sepsis recognition and treatment in all patients,” including those without comorbidities, Chanu Rhee, MD, said at an annual scientific meeting on infectious diseases. He hypothesized that the increased sepsis mortality among previously healthy patients may have stemmed from factors such as delayed sepsis recognition resulting in hospitalization at a more advanced stage and less aggressive management.

In addition, “the findings provide context for high-profile reports about sepsis death in previously healthy people,” said Dr. Rhee, an infectious diseases and critical care physician at Brigham and Women’s Hospital in Boston. Dr. Rhee and associates found that, among patients hospitalized with what the researchers defined as “community-acquired” sepsis, 3% were judged previously healthy by having no identified major or minor comorbidity or pregnancy at the time of hospitalization, a percentage that – while small – still translates into roughly 40,000 such cases annually in the United States. That helps explain why every so often a headline appears about a famous person who died suddenly and unexpectedly from sepsis, he noted.

The study used data collected on hospitalized U.S. patients in the Cerner Health Facts, HCA Healthcare, and Institute for Health Metrics and Evaluation databases, which included about 6.7 million people total including 337,983 identified as having community-acquired sepsis, defined as patients who met the criteria for adult sepsis advanced by the Centers for Disease Control and Prevention within 2 days of their hospital admission. The researchers looked further into the hospital records of these patients and divided them into patients with one or more major comorbidities (96% of the cohort), patients who were pregnant or had a “minor” comorbidity such as a lipid disorder, benign neoplasm, or obesity (1% of the study group), or those with no chronic comorbidity (3%; the subgroup the researchers deemed previously healthy).

In a multivariate analysis that adjusted for patients’ age, sex, race, infection site, and illness severity at the time of hospital admission the researchers found that the rate of in-hospital death among the previously healthy patients was exactly twice the rate of those who had at least one major chronic comorbidity, Dr. Rhee reported. Differences in the treatment received by the previously-healthy patients or in their medical status compared with patients with a major comorbidity suggested that the previously health patients were sicker. They had a higher rate of mechanical ventilation, 30%, compared with about 18% for those with a comorbidity; a higher rate of acute kidney injury, about 43% in those previously healthy and 28% in those with a comorbidity; and a higher percentage had an elevated lactate level, about 41% among the previously healthy patients and about 22% among those with a comorbidity.

[email protected]

SOURCE: Alrawashdeh M et al. Open Forum Infect Dis. 2019 Oct 23;6. Abstract 891.

WASHINGTON – Influenza vaccine continues to cut not just the incidence of flu but also mitigates infection severity in both children and adults, according to recent U.S. experience collected by the Centers for Disease Control and Prevention.

During recent U.S. flu seasons, children and adults who contracted influenza despite vaccination had significantly fewer severe infections and infection complications, compared with unimmunized people, according to two separate reports from CDC researchers presented at an annual scientific meeting on infectious diseases.

One of the reports tracked the impact of flu vaccine in children using data that the CDC collected at seven medical centers that participated in the agency’s New Vaccine Surveillance Network, which provided information on children aged 6 months to 17 years who were hospitalized for an acute respiratory illness, including more than 1,700 children during the 2016-2017 flu season and more than 1,900 during the 2017-2018 season. Roughly 10% of these children tested positive for influenza, and the subsequent analysis focused on these cases and compared incidence rates among children who had been vaccinated during the index season and those who had remained unvaccinated.

Combined data from both seasons showed that vaccinated children were 50% less likely to have been hospitalized for an acute influenza infection, compared with unvaccinated kids, a pattern consistently seen both in children aged 6 months to 8 years and in those aged 9-17 years. The pattern of vaccine effectiveness also held regardless of which flu strain caused the infections, reported Angela P. Campbell, MD, a CDC medical officer.

“We saw a nice benefit from vaccination, both in previously healthy children and in those with an underlying medical condition,” a finding that adds to existing evidence of vaccine effectiveness, Dr. Campbell said in a video interview. The results confirmed that flu vaccination does not just prevent infections but also cuts the rate of more severe infections that lead to hospitalization, she explained.

Another CDC study looked at data collected by the agency’s Influenza Hospitalization Surveillance Network from adults at least 18 years old who were hospitalized for a laboratory-confirmed influenza infection during five flu seasons, 2013-2014 through 2017-18. The data, which came from more than 250 acute-care hospitals in 13 states, included more than 43,000 people hospitalized for an identified influenza strain and with a known vaccination history who were not institutionalized and had not received any antiviral treatment.

After propensity-weighted adjustment to create better parity between the vaccinated and unvaccinated patients, the results showed that people 18-64 years old with vaccination had statistically significant decreases in mortality of a relative 36%, need for mechanical ventilation of 34%, pneumonia of 20%, and need for ICU admission of a relative 19%, as well as an 18% drop in average ICU length of stay, Shikha Garg, MD, said at the meeting. The propensity-weighted analysis of data from people at least 65 years old showed statistically significant relative reductions linked with vaccination: 46% reduction in the need for mechanical ventilation, 28% reduction in ICU admissions, and 9% reduction in hospitalized length of stay.

Further analysis of these outcomes by the strains that caused these influenza infections showed that the statistically significant benefits from vaccination were seen only in patients infected with an H1N1 strain. Statistically significant effects on these severe outcomes were not apparent among people infected with the H3N2 or B strains, said Dr. Garg, a medical epidemiologist at the CDC.

“All adults should receive an annual flu vaccination as it can improve outcomes among those who develop influenza despite vaccination,” she concluded.

Results from a third CDC study reported at the meeting examined the importance of two vaccine doses (administered at least 4 weeks apart) given to children aged 6 months to 8 years for the first season they receive flu vaccination, which is the immunization approach for flu recommended by the CDC. The findings from a total of more than 7,500 children immunized during the 2014-2018 seasons showed a clear increment in vaccine protection among kids who received two doses during their first season vaccinated, especially in children who were 2 years old or younger. In that age group, administration of two doses produced vaccine effectiveness of 53% versus a 23% vaccine effectiveness after a single vaccine dose, reported Jessie Chung, a CDC epidemiologist.

[email protected]

WASHINGTON – Influenza vaccine continues to cut not just the incidence of flu but also mitigates infection severity in both children and adults, according to recent U.S. experience collected by the Centers for Disease Control and Prevention.

During recent U.S. flu seasons, children and adults who contracted influenza despite vaccination had significantly fewer severe infections and infection complications, compared with unimmunized people, according to two separate reports from CDC researchers presented at an annual scientific meeting on infectious diseases.

One of the reports tracked the impact of flu vaccine in children using data that the CDC collected at seven medical centers that participated in the agency’s New Vaccine Surveillance Network, which provided information on children aged 6 months to 17 years who were hospitalized for an acute respiratory illness, including more than 1,700 children during the 2016-2017 flu season and more than 1,900 during the 2017-2018 season. Roughly 10% of these children tested positive for influenza, and the subsequent analysis focused on these cases and compared incidence rates among children who had been vaccinated during the index season and those who had remained unvaccinated.

Combined data from both seasons showed that vaccinated children were 50% less likely to have been hospitalized for an acute influenza infection, compared with unvaccinated kids, a pattern consistently seen both in children aged 6 months to 8 years and in those aged 9-17 years. The pattern of vaccine effectiveness also held regardless of which flu strain caused the infections, reported Angela P. Campbell, MD, a CDC medical officer.

“We saw a nice benefit from vaccination, both in previously healthy children and in those with an underlying medical condition,” a finding that adds to existing evidence of vaccine effectiveness, Dr. Campbell said in a video interview. The results confirmed that flu vaccination does not just prevent infections but also cuts the rate of more severe infections that lead to hospitalization, she explained.

Another CDC study looked at data collected by the agency’s Influenza Hospitalization Surveillance Network from adults at least 18 years old who were hospitalized for a laboratory-confirmed influenza infection during five flu seasons, 2013-2014 through 2017-18. The data, which came from more than 250 acute-care hospitals in 13 states, included more than 43,000 people hospitalized for an identified influenza strain and with a known vaccination history who were not institutionalized and had not received any antiviral treatment.

After propensity-weighted adjustment to create better parity between the vaccinated and unvaccinated patients, the results showed that people 18-64 years old with vaccination had statistically significant decreases in mortality of a relative 36%, need for mechanical ventilation of 34%, pneumonia of 20%, and need for ICU admission of a relative 19%, as well as an 18% drop in average ICU length of stay, Shikha Garg, MD, said at the meeting. The propensity-weighted analysis of data from people at least 65 years old showed statistically significant relative reductions linked with vaccination: 46% reduction in the need for mechanical ventilation, 28% reduction in ICU admissions, and 9% reduction in hospitalized length of stay.

Further analysis of these outcomes by the strains that caused these influenza infections showed that the statistically significant benefits from vaccination were seen only in patients infected with an H1N1 strain. Statistically significant effects on these severe outcomes were not apparent among people infected with the H3N2 or B strains, said Dr. Garg, a medical epidemiologist at the CDC.

“All adults should receive an annual flu vaccination as it can improve outcomes among those who develop influenza despite vaccination,” she concluded.

Results from a third CDC study reported at the meeting examined the importance of two vaccine doses (administered at least 4 weeks apart) given to children aged 6 months to 8 years for the first season they receive flu vaccination, which is the immunization approach for flu recommended by the CDC. The findings from a total of more than 7,500 children immunized during the 2014-2018 seasons showed a clear increment in vaccine protection among kids who received two doses during their first season vaccinated, especially in children who were 2 years old or younger. In that age group, administration of two doses produced vaccine effectiveness of 53% versus a 23% vaccine effectiveness after a single vaccine dose, reported Jessie Chung, a CDC epidemiologist.

[email protected]

WASHINGTON – Influenza vaccine continues to cut not just the incidence of flu but also mitigates infection severity in both children and adults, according to recent U.S. experience collected by the Centers for Disease Control and Prevention.

During recent U.S. flu seasons, children and adults who contracted influenza despite vaccination had significantly fewer severe infections and infection complications, compared with unimmunized people, according to two separate reports from CDC researchers presented at an annual scientific meeting on infectious diseases.

One of the reports tracked the impact of flu vaccine in children using data that the CDC collected at seven medical centers that participated in the agency’s New Vaccine Surveillance Network, which provided information on children aged 6 months to 17 years who were hospitalized for an acute respiratory illness, including more than 1,700 children during the 2016-2017 flu season and more than 1,900 during the 2017-2018 season. Roughly 10% of these children tested positive for influenza, and the subsequent analysis focused on these cases and compared incidence rates among children who had been vaccinated during the index season and those who had remained unvaccinated.

Combined data from both seasons showed that vaccinated children were 50% less likely to have been hospitalized for an acute influenza infection, compared with unvaccinated kids, a pattern consistently seen both in children aged 6 months to 8 years and in those aged 9-17 years. The pattern of vaccine effectiveness also held regardless of which flu strain caused the infections, reported Angela P. Campbell, MD, a CDC medical officer.

“We saw a nice benefit from vaccination, both in previously healthy children and in those with an underlying medical condition,” a finding that adds to existing evidence of vaccine effectiveness, Dr. Campbell said in a video interview. The results confirmed that flu vaccination does not just prevent infections but also cuts the rate of more severe infections that lead to hospitalization, she explained.

Another CDC study looked at data collected by the agency’s Influenza Hospitalization Surveillance Network from adults at least 18 years old who were hospitalized for a laboratory-confirmed influenza infection during five flu seasons, 2013-2014 through 2017-18. The data, which came from more than 250 acute-care hospitals in 13 states, included more than 43,000 people hospitalized for an identified influenza strain and with a known vaccination history who were not institutionalized and had not received any antiviral treatment.

After propensity-weighted adjustment to create better parity between the vaccinated and unvaccinated patients, the results showed that people 18-64 years old with vaccination had statistically significant decreases in mortality of a relative 36%, need for mechanical ventilation of 34%, pneumonia of 20%, and need for ICU admission of a relative 19%, as well as an 18% drop in average ICU length of stay, Shikha Garg, MD, said at the meeting. The propensity-weighted analysis of data from people at least 65 years old showed statistically significant relative reductions linked with vaccination: 46% reduction in the need for mechanical ventilation, 28% reduction in ICU admissions, and 9% reduction in hospitalized length of stay.

Further analysis of these outcomes by the strains that caused these influenza infections showed that the statistically significant benefits from vaccination were seen only in patients infected with an H1N1 strain. Statistically significant effects on these severe outcomes were not apparent among people infected with the H3N2 or B strains, said Dr. Garg, a medical epidemiologist at the CDC.

“All adults should receive an annual flu vaccination as it can improve outcomes among those who develop influenza despite vaccination,” she concluded.

Results from a third CDC study reported at the meeting examined the importance of two vaccine doses (administered at least 4 weeks apart) given to children aged 6 months to 8 years for the first season they receive flu vaccination, which is the immunization approach for flu recommended by the CDC. The findings from a total of more than 7,500 children immunized during the 2014-2018 seasons showed a clear increment in vaccine protection among kids who received two doses during their first season vaccinated, especially in children who were 2 years old or younger. In that age group, administration of two doses produced vaccine effectiveness of 53% versus a 23% vaccine effectiveness after a single vaccine dose, reported Jessie Chung, a CDC epidemiologist.

[email protected]

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

[email protected]

SOURCE: Garg S. ID Week 2019, Abstract LB19.

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

[email protected]

SOURCE: Garg S. ID Week 2019, Abstract LB19.

WASHINGTON – People may differ in their susceptibility to different influenza subtypes based in part on the year when they were born and the flu strains that circulated during their birth year, according to infection patterns during a recent U.S. flu season.

“Our findings may indicate protection against H1 [influenza] viruses in age groups with early exposure to H1N1pdm09 during the 2009 pandemic or to older, antigenically similar H1N1 viruses,” Shikha Garg, MD, said at an annual scientific meeting on infectious diseases. If results from further studies confirm this relationship it could have implications for flu vaccine effectiveness in various age groups and influence the composition of flu vaccines based on the ages of the people who will receive them, said Dr. Garg, a medical epidemiologist with the Centers for Disease Control and Prevention in Atlanta.

The analysis she reported using data collected by the CDC’s Influenza Hospitalization Surveillance Network on 18,699 people hospitalized for influenza infection during the 2018-2019 season, Oct. 1, 2018–April 30, 2019. The database provides a representative sampling of patients hospitalized for influenza at more than 250 acute care hospitals in 13 states. During the season studied, both the H1N1 and H3N2 subtypes circulated and caused similar cumulative rates of infections, with H1N1 causing about 32 confirmed cases per 100,000 people and H3N2 causing about 29 cases/100,000.

But a more granular analysis that divided the hospitalized patients by their birth year showed an excess of H1N1 infections in two demographic slices: those born during 2010-2019 (corresponding to children 0-9 years old), in whom H1N1 accounted for roughly 60% of cases; and also in those born during 1948-1995 (people aged 24-70 years old) in whom H1N1 caused roughly 70% or more of all infections in some for some birth-year groups in this demographic range. In contrast, infection with the circulating H3N2 strain in the 2018-2019 season dominated among those born during 1996-2009 (people aged 10-23), as well as in those born in 1947 or earlier (those who were at least 71 years old). Some age groups within those born in 1996-2009 had H3N2 infection rates that made up 70% or more of all flu infections, and among nonagenarians well over three-quarters of flu infection were by the H3N2 subtype.

Dr. Garg also showed a similar pattern of predominant flu subtype by age using U.S. influenza hospitalization data for the 2017-2018 season, as well as for all types of 2018-2019 U.S. influenza infections that underwent strain typing including outpatients as well as in patients. All of these findings support the hypothesis and extend the data published earlier this year by Dr. Garg and several of her CDC colleagues that described a pattern of “antigen imprinting” that appeared caused by influenza exposure during the first year of life (J Infect Dis. 2019 Sep 1;220[5]:820-9). However, more data are needed to better assess time trends for children who were first exposed to H1N1 influenza during the 2009 pandemic, Dr. Garg said.

[email protected]

SOURCE: Garg S. ID Week 2019, Abstract LB19.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

[email protected]

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

[email protected]

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

WASHINGTON – A single dose of a novel monoclonal antibody against a respiratory syncytial virus surface protein safely protected preterm infants against severe infections for 150 days during their first winter season in a randomized trial with more than 1,400 children.

copyright DesignPics/Thinkstock

One intramuscular injection of nirsevimab (also known as MEDI8897) administered to infants born at 29-35 weeks’ gestation at the start of the local respiratory syncytial virus (RSV) season (November in the Northern hemisphere) led to a 70% relative reduction in the rate of medically attended lower respiratory tract infections with RSV during the subsequent 150 days, compared with placebo, the study’s primary efficacy outcome, M. Pamela Griffin, MD, said at an annual scientific meeting on infectious diseases.

In a secondary efficacy measure, the rate of hospitalizations for RSV-caused lower respiratory tract infections, a single injection of nirsevimab dropped the incidence by 78%, relative to placebo. Both effects were statistically significant. The rate of total adverse events and serious adverse events was similar in the two treatment arms, reported Dr. Griffin, a clinical development lead with AstraZeneca.

These positive results for a single intramuscular injection of nirsevimab are the first findings from a series of studies aimed at getting the monoclonal antibody onto the U.S. market as a superior alternative to palivizumab (Synagis), which acts in a similar way to block RSV infection (albeit by targeting a different viral surface protein) but which requires administration every 30 days. This need for serial dosing of palivizumab in children younger than 1 year old for complete seasonal protection against RSV is probably a reason why the American Academy of Pediatrics, as well as other medical societies, have targeted using palivizumab only on certain types of high-risk infants: those born before 29 weeks’ gestational age, with chronic lung disease of prematurity, or with hemodynamically significant congenital heart disease (Pediatrics. 2014 Aug;134[2]:415-20). “It’s not feasible for most infants to come for five treatments during RSV season,” Dr. Griffin noted. A tweak in the structure of nirsevimab gives it a much longer blood half-life than palivizumab and allows a single dose to maintain efficacy for 5 months, the duration of RSV season.

“The big advantage of nirsevimab is one dose instead of five,” she said in an interview.

The study randomized 969 preterm infants to nirsevimab and 484 to placebo when the children averaged 3 months old and 4.5 kg. The incidence of the primary endpoint was 2.6% in the nirsevimab-treated infants and 9.5% in those who received placebo. The incidence of hospitalizations associated with an RSV lower respiratory tract infection was 0.8% in the nirsevimab group and 4.1% on placebo. Nirsevimab was equally effective regardless of RSV subtype, infant age, or sex. The rate of hypersensitivity reactions was low, less than 1%, and similar in the two treatment arms, as was the rate of detection of antidrug antibody, 3.8% with placebo and 5.6% with nirsevimab.

Two other large trials are underway to document the performance of nirsevimab in other types of infants. One study is examining the drug’s performance compared with placebo in term infants with a gestational age of at least 36 weeks, while another is comparing nirsevimab against a five-dose regimen of palivizumab in high-risk infants who are recommended to receive palivizumab by local medical societies. In the United States, this would be infants born at less than 29 weeks’ gestation, and those with either hemodynamically significant congenital heart disease or chronic lung disease of prematurity. In these studies, the researchers also will assess the cost effectiveness of nirsevimab relative to the costs for medical care needed by infants who receive comparator treatments, Dr. Griffin said.

The study was funded by AstraZeneca, the company developing nirsevimab. Dr. Griffin is an employee of and shareholder in AstraZeneca.

[email protected]

SOURCE: ClinicalTrials.gov identifier: NCT02878330.

WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.

Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.

The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.

Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.

Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.

Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.

The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.

“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.

The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.

[email protected]

WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.

Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.

The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.

Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.

Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.

Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.

The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.

“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.

The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.

[email protected]

WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.

Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.

The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.

Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.

Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.

Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.

The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.

“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.

The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.

[email protected]

WASHINGTON – Evidence continues to mount that infants born to moms infected with Zika virus during pregnancy can have neurodevelopmental abnormalities as they age even if they showed no defects at birth, based on follow-up of 890 Colombian children tracked by epidemiologists from the U.S. Centers for Disease Control and Prevention.

Among the 890 neonates born to mothers apparently infected with Zika during pregnancy and followed for up to 2 years, 40 of the 852 (5%) without a detectable birth defect at delivery went on to show some type of neurodevelopmental sequelae during up to 24 months of age, Margaret Honein, PhD, said at an annual scientific meeting on infectious diseases.

In addition, among the children without birth defects at delivery who received follow-up examinations out to about 2 years, the incidence of “alerts” for possible neurodevelopmental issues was 15%-20% for each of the four domains studied (gross motor, fine motor, hearing and language, and personal and social functions), said Dr. Honein, an epidemiologist and chief of the birth defects branch of the CDC. In contrast, 17 of the 38 children (45%) followed who had identifiable birth defects at delivery also showed neurodevelopmental abnormalities when reexamined as long as 2 years after birth. These possible neurodevelopmental abnormalities, designated as alerts, were identified in comparison with a contemporaneous cohort of children born to uninfected mothers in the same regions of Colombia and assessed by the CDC researchers.

This cohort of children born to mothers who became infected with Zika virus during the 2016 Colombian epidemic will not undergo any planned, additional follow-up beyond the initial 2 years, Dr. Honein noted.

The findings she reported were consistent with observations from a much smaller cohort of 70 infants born to Colombian mothers infected with Zika virus while pregnant who had a normal head circumference and a normal clinical examination at delivery. When assessed once or twice 4-18 months after birth, these 70 infants showed an overall greater than one standard deviation (z-score) drop in their scores on the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) metric by 12 months after birth and continuing out to 18 months, said Sarah B. Mulkey, MD, a fetal-neonatal neurologist at Children’s National Health System in Washington. These deficits were especially pronounced in the mobility and social cognition domains of the four-domain WIDEA metric. The social cognition domain is an important predictor of later problems with executive function and other neurologic disorders, Dr. Mulkey said while reporting her findings in a separate talk at the meeting. She acknowledged that the analysis was flawed by comparing the WIDEA outcomes of the Zika virus–exposed children to healthy children from either inner-city Chicago or Canada. Dr. Mulkey said that she and her associates plan to characterize a population of Zika virus–unexposed children in Colombia to use for future comparisons.

The study reported by Dr. Honein involved an enhanced surveillance program launched by the CDC in 2016 in three regions of Colombia and included 1,190 pregnancies accompanied by Zika symptoms in the mother and with a reported pregnancy outcome, including 1,185 live births. Nearly half of the Zika infections occurred during the first trimester, and 34% occurred during the second trimester. However, fewer than a third of the pregnant women underwent some type of laboratory testing to confirm their infection, either by serology or by a DNA-based assay, and of these 28% had a positive finding. Dr. Honein cautioned that many of the specimens that tested negative for Zika virus may have been false negatives.

The birth defects identified among the infants born from an apparently affected pregnancy included brain abnormalities, eye anomalies, and microcephaly, with 5% of the 1,185 live births showing one or more of these outcomes. The neurodevelopmental deficits identified during follow-up of 890 of the children out to 2 years included seizures; abnormalities of tone, movement, or swallowing; and impairments of vision or hearing.

[email protected]

WASHINGTON – Evidence continues to mount that infants born to moms infected with Zika virus during pregnancy can have neurodevelopmental abnormalities as they age even if they showed no defects at birth, based on follow-up of 890 Colombian children tracked by epidemiologists from the U.S. Centers for Disease Control and Prevention.

Among the 890 neonates born to mothers apparently infected with Zika during pregnancy and followed for up to 2 years, 40 of the 852 (5%) without a detectable birth defect at delivery went on to show some type of neurodevelopmental sequelae during up to 24 months of age, Margaret Honein, PhD, said at an annual scientific meeting on infectious diseases.

In addition, among the children without birth defects at delivery who received follow-up examinations out to about 2 years, the incidence of “alerts” for possible neurodevelopmental issues was 15%-20% for each of the four domains studied (gross motor, fine motor, hearing and language, and personal and social functions), said Dr. Honein, an epidemiologist and chief of the birth defects branch of the CDC. In contrast, 17 of the 38 children (45%) followed who had identifiable birth defects at delivery also showed neurodevelopmental abnormalities when reexamined as long as 2 years after birth. These possible neurodevelopmental abnormalities, designated as alerts, were identified in comparison with a contemporaneous cohort of children born to uninfected mothers in the same regions of Colombia and assessed by the CDC researchers.

This cohort of children born to mothers who became infected with Zika virus during the 2016 Colombian epidemic will not undergo any planned, additional follow-up beyond the initial 2 years, Dr. Honein noted.

The findings she reported were consistent with observations from a much smaller cohort of 70 infants born to Colombian mothers infected with Zika virus while pregnant who had a normal head circumference and a normal clinical examination at delivery. When assessed once or twice 4-18 months after birth, these 70 infants showed an overall greater than one standard deviation (z-score) drop in their scores on the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) metric by 12 months after birth and continuing out to 18 months, said Sarah B. Mulkey, MD, a fetal-neonatal neurologist at Children’s National Health System in Washington. These deficits were especially pronounced in the mobility and social cognition domains of the four-domain WIDEA metric. The social cognition domain is an important predictor of later problems with executive function and other neurologic disorders, Dr. Mulkey said while reporting her findings in a separate talk at the meeting. She acknowledged that the analysis was flawed by comparing the WIDEA outcomes of the Zika virus–exposed children to healthy children from either inner-city Chicago or Canada. Dr. Mulkey said that she and her associates plan to characterize a population of Zika virus–unexposed children in Colombia to use for future comparisons.

The study reported by Dr. Honein involved an enhanced surveillance program launched by the CDC in 2016 in three regions of Colombia and included 1,190 pregnancies accompanied by Zika symptoms in the mother and with a reported pregnancy outcome, including 1,185 live births. Nearly half of the Zika infections occurred during the first trimester, and 34% occurred during the second trimester. However, fewer than a third of the pregnant women underwent some type of laboratory testing to confirm their infection, either by serology or by a DNA-based assay, and of these 28% had a positive finding. Dr. Honein cautioned that many of the specimens that tested negative for Zika virus may have been false negatives.

The birth defects identified among the infants born from an apparently affected pregnancy included brain abnormalities, eye anomalies, and microcephaly, with 5% of the 1,185 live births showing one or more of these outcomes. The neurodevelopmental deficits identified during follow-up of 890 of the children out to 2 years included seizures; abnormalities of tone, movement, or swallowing; and impairments of vision or hearing.

[email protected]

WASHINGTON – Evidence continues to mount that infants born to moms infected with Zika virus during pregnancy can have neurodevelopmental abnormalities as they age even if they showed no defects at birth, based on follow-up of 890 Colombian children tracked by epidemiologists from the U.S. Centers for Disease Control and Prevention.

Among the 890 neonates born to mothers apparently infected with Zika during pregnancy and followed for up to 2 years, 40 of the 852 (5%) without a detectable birth defect at delivery went on to show some type of neurodevelopmental sequelae during up to 24 months of age, Margaret Honein, PhD, said at an annual scientific meeting on infectious diseases.

In addition, among the children without birth defects at delivery who received follow-up examinations out to about 2 years, the incidence of “alerts” for possible neurodevelopmental issues was 15%-20% for each of the four domains studied (gross motor, fine motor, hearing and language, and personal and social functions), said Dr. Honein, an epidemiologist and chief of the birth defects branch of the CDC. In contrast, 17 of the 38 children (45%) followed who had identifiable birth defects at delivery also showed neurodevelopmental abnormalities when reexamined as long as 2 years after birth. These possible neurodevelopmental abnormalities, designated as alerts, were identified in comparison with a contemporaneous cohort of children born to uninfected mothers in the same regions of Colombia and assessed by the CDC researchers.

This cohort of children born to mothers who became infected with Zika virus during the 2016 Colombian epidemic will not undergo any planned, additional follow-up beyond the initial 2 years, Dr. Honein noted.

The findings she reported were consistent with observations from a much smaller cohort of 70 infants born to Colombian mothers infected with Zika virus while pregnant who had a normal head circumference and a normal clinical examination at delivery. When assessed once or twice 4-18 months after birth, these 70 infants showed an overall greater than one standard deviation (z-score) drop in their scores on the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) metric by 12 months after birth and continuing out to 18 months, said Sarah B. Mulkey, MD, a fetal-neonatal neurologist at Children’s National Health System in Washington. These deficits were especially pronounced in the mobility and social cognition domains of the four-domain WIDEA metric. The social cognition domain is an important predictor of later problems with executive function and other neurologic disorders, Dr. Mulkey said while reporting her findings in a separate talk at the meeting. She acknowledged that the analysis was flawed by comparing the WIDEA outcomes of the Zika virus–exposed children to healthy children from either inner-city Chicago or Canada. Dr. Mulkey said that she and her associates plan to characterize a population of Zika virus–unexposed children in Colombia to use for future comparisons.

The study reported by Dr. Honein involved an enhanced surveillance program launched by the CDC in 2016 in three regions of Colombia and included 1,190 pregnancies accompanied by Zika symptoms in the mother and with a reported pregnancy outcome, including 1,185 live births. Nearly half of the Zika infections occurred during the first trimester, and 34% occurred during the second trimester. However, fewer than a third of the pregnant women underwent some type of laboratory testing to confirm their infection, either by serology or by a DNA-based assay, and of these 28% had a positive finding. Dr. Honein cautioned that many of the specimens that tested negative for Zika virus may have been false negatives.

The birth defects identified among the infants born from an apparently affected pregnancy included brain abnormalities, eye anomalies, and microcephaly, with 5% of the 1,185 live births showing one or more of these outcomes. The neurodevelopmental deficits identified during follow-up of 890 of the children out to 2 years included seizures; abnormalities of tone, movement, or swallowing; and impairments of vision or hearing.

[email protected]

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – The top existential threats to health today are climate change and overpopulation, but third in this list is antimicrobial resistance, according to Helen Boucher, MD, of Tufts Medical Center, Boston. In her talk at an annual scientific meeting on infectious diseases, however, she focused on the last, presenting the hottest developments in the clinical science of treating and identifying disease-causing agents.

In particular, she discussed two of the most important developments in the area of rapid diagnostics: cell-free microbial DNA in plasma and the use of next-generation gene sequencing for determining disease etiology.

Using a meta-genomics test, cell-free microbial DNA can be identified in plasma from more than 1,000 relevant bacteria, DNA viruses, fungi, and parasites. Though importantly, RNA viruses are not detectable using this technology, she added. Although current sampling is of plasma, this might expand to the ability to use urine in the future. She discussed its particular use in sepsis, as outlined in a paper in Nature Microbiology (2019;4[4]:663-74). The researchers examined 350 suspected sepsis patients and they found a 93% sensitivity, compared with reference standards, using this new test. The main issue with the test was a high incidence of false positives.

Another test Dr. Boucher discussed was the use of meta-genomic next-generation sequencing. She referred to a 2019 paper in the New England Journal of Medicine, which discussed the use of clinical meta-genomic next-generation sequencing of cerebrospinal fluid for the diagnosis of meningitis and encephalitis (2019;380[27]:2327-40). Next-generation sequencing identified 13% of patients positive who were missed using standard screening. However, a number of patients were not diagnosed using the new test, showing that this technique was an improvement over current methods, but not 100% successful.

Dr. Boucher stressed the need for “diagnostic stewardship” to identify the correct microbial agent causing disease, allowing for the use of appropriate treatment rather than shotgun approaches to prevent the development of antibiotic resistance. This practice requires collaboration between the clinical laboratory, pharmacists, and infectious disease specialists.

Dr. Boucher then switched to the area of therapeutics, focusing on the introduction of new antibiotics and other innovations in disease treatment methodologies, especially in the field of transplant ID.

“We have new drugs. That is the good news,” with the goals of the 10 x ’20 initiative to develop 10 new systemic antibiotics by 2020, having “been met and then some,” said Dr. Boucher.

“We now have 13 new drugs, systemically available antibiotics, available by August 2019,” she added, discussing several of the new drugs.

In addition, she pointed out several studies that have indicated that shorter courses of antibiotics are better than longer, and that, in many cases, oral therapy is better than intravenous.

In the burgeoning area of transplant ID studies, Dr. Boucher discussed new research showing that vaccinations in transplanted patients can be advised in several instances, though may require higher dosing, and how the use of hepatitis C virus–positive organs for transplant is showing good results and increasing the availability of organs for transplant.

Dr. Boucher has served on data review committees for Actelion and Medtronix and has served as a consultant/advisor for Cerexa, Durata Therapeutics, Merck (adjudication committee), Rib-X, and Wyeth/Pfizer (data safety monitoring committee).

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

WASHINGTON – Patients hospitalized for pyelonephritis and discharged after receiving intravenous antibiotic treatment who then received step-down treatment with an oral beta-lactam had 30-day outcomes that were noninferior to patients who received an oral fluoroquinolone or trimethoprim-sulfamethoxazole as their discharge regimen, in a retrospective study of 211 patients managed at either of two U.S. hospitals.

This was the largest comparison reported on oral beta-lactam drugs for postdischarge treatment of pyelonephritis relative to the standard oral agents, fluoroquinolones and trimethoprim-sulfamethoxazole (Bactrim), Athena Hobbs, PharmD, said at an annual scientific meeting on infectious diseases. The superiority of an oral fluoroquinolone or trimethoprim-sulfamethoxazole and inferiority of oral beta-lactam drugs were cited in 2010 guidelines for managing pyelonephritis from the Infectious Diseases Society of America (Clin Infect Dis. 2011 March 1;52 [5]: e103-20).

Although limited as a nonrandomized, retrospective comparison, the finding of at least similar efficacy by beta-lactam agents “opens new treatment options” that avoid issues with drug resistance and adverse effects from treatment with fluoroquinolones or trimethoprim-sulfamethoxazole, Dr. Hobbs said in a video interview. Beta-lactams have already been embraced for this indication by some hospitalists, demonstrated by their use of beta-lactam antibiotics for 122 (58%) of the 211 patients included in the study. Among the 89 patients discharged on a non–beta-lactam, 69 (78%) had fluoroquinolone treatment and the remaining 20 patients went home taking trimethoprim-sulfamethoxazole. The new finding “confirms that we are not doing harm to patients,” with this existing practice of mostly prescribing an oral beta-lactam drug, noted Dr. Hobbs, an infectious diseases pharmacy specialist at Baptist Memorial Hospital in Memphis.

The study included patients aged 18-89 years hospitalized during 2014-2017 for a primary diagnosis of pyelonephritis at Baptist or at a second Hospital in Austin, Tex. The study excluded patients in intensive care, with a urologic abnormality, pregnant women, and patients treated with an intravenous antibiotic other than a beta-lactam for more than 24 hours. The most commonly used intravenous drugs were cefazolin and ceftriaxone. The enrolled patients averaged just over 40 years old, and more than 90% were women.

The study’s primary outcome was the 30-day rate of either hospital readmission or an ED visit for pyelonephritis or a urinary tract infection. This occurred in 4.9% of the patients discharged on an oral course of a beta-lactam drug, and in 5.6% of those discharged on either a fluoroquinolone or trimethoprim-sulfamethoxazole, a difference that was not statistically significant and that met the prespecified criteria for noninferiority, Dr. Hobbs reported. The most commonly prescribed oral beta-lactam was cefuroxime in about half the patients, followed by cephalexin or cefadroxil in about a quarter of patients, and amoxicillin with clavulanate in 19%. The two arms of the study also showed no significant difference in infection recurrences during 90-day follow-up.

The study received no commercial funding. Dr. Hobbs had no relevant disclosures.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

[email protected]

WASHINGTON – An investigational, oral, small molecule designed to boost innate antiviral immunity safely cut the incidence of various viral respiratory infections in elderly people during a winter season by nearly a third when administered once daily in a placebo-controlled, multicenter, phase 2 study of 952 patients. Based on these and other findings the drug, RTB101, is now undergoing testing in a phase 3 study, Joan Mannick, MD, said at an annual scientific meeting on infectious diseases.

Mitchel L. Zoler/MDedge News

At a dosage of 10 mg once daily, RTB101 was “well tolerated, upregulated innate antiviral gene expression, and reduced the incidence” of laboratory-confirmed respiratory tract infections caused by several different viruses, said Dr. Mannick, who disclosed that she is a cofounder and chief medical officer of resTORbio, a Boston-based company that’s developing the drug.

During 16 weeks of treatment during the winter virus season, once-daily dosing led to cuts in the rates of respiratory infections compared with placebo by rhinovirus and enterovirus, respiratory syncytial virus, coronavirus, influenza virus, metapneuomovirus, and parainfluenza virus, especially in patients whom the results identified as having the best drug responses: those who were at least 85 years old, and those who were at least 65 years old and also had asthma. Enrolled patients who were at least 65 years old and had other risk factors – current smoking, chronic obstructive pulmonary disease, or diabetes – had notably less robust responses to treatment, and the phase 3 study is not enrolling elderly people who currently smoke or have chronic obstructive pulmonary disease, Dr. Mannick said in an interview.

RTB101 inhibits the active site of the “mechanistic target of rapamycin” (mTOR) protein, the key player of the TORC1 protein complex that appears to downregulate innate antiviral immunity when active. Hence inhibiting mTOR and TORC1 activity should boost innate antiviral immunity. Once-daily dosing with 10 mg of RTB101 appears to mimic the normal daily cycle of high and low levels of TORC1 activity seen in younger adults but which is missing the elderly who generally have persistently elevated levels of TORC1 activity, Dr. Mannick explained.

The study she reported enrolled a total of 952 people at any of 10 sites in the Southern Hemisphere or 17 Northern Hemisphere study sites. The researchers randomized patients to receive either RTB101 or placebo at either of two once-daily dosages or either of two twice-daily regimens. The best drug performance was among the 356 patients treated with 10 mg once daily or placebo. Those who received the active drug at this level had a 19% incidence of any laboratory-confirmed respiratory tract infection, while those who received placebo had a 28% incidence, a 30.6% relative risk reduction with RTB101 treatment that was statistically significant.

The actively-treated patients showed upregulation for 19 of 20 “antiviral” genes assessed in the study compared with upregulation of just five of these genes in the those who received placebo. Two post hoc analyses showed that the people who received 10 mg once daily had about half the rate of all-cause hospitalizations compared with those on placebo, and among those who had respiratory infections treated patients had alleviation of their moderate or severe symptoms in about half the time compared with patients on placebo.

The 10-mg daily dosage of RTB101 is less than 1% of the maximum-tolerated dose in people, and the safety data collected in the current study showed adverse events occurring at similar rates in the patients who received the active drug and those who got placebo. Discontinuations because of adverse events occurred in 5% of people who received RTB101 and in 6% of those on placebo.

The researchers are planning to run a cost-effectiveness study to see whether the observed prevention of respiratory tract infections and their consequences can offset the cost of taking RTB101 daily for 16 weeks, Dr. Mannick said.

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