Jim Kling

SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.

CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.

Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.

CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.

The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.

Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.

The philosophy behind CAMS is to promote collaborative management between the patient and clinician. The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.

The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.

Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.

CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.

Dr. Adrian has no conflicts of interest or disclosures.

SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.

CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.

Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.

CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.

The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.

Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.

The philosophy behind CAMS is to promote collaborative management between the patient and clinician. The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.

The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.

Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.

CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.

Dr. Adrian has no conflicts of interest or disclosures.

SEATTLE – When it comes to treating children and adolescents who have experienced trauma and present suicidality, it is not just the patients who need support. Clinicians also experience grave anxiety when dealing with a traumatized child exhibiting suicidal behavior. The Collaborative Assessment and Management of Suicide (CAMS) framework can help clinicians or health care workers manage the care of these challenging patients.

CAMS is well established in adults with suicidal behavior, but it is unproven in youth and adolescents. The key is to its success in younger patients will be whether the program is developmentally appropriate, according to Molly C. Adrian, PhD, assistant professor of psychiatry and behavioral medicine at the University of Washington, Seattle. Dr. Adrian discussed CAMS and its potential applications at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The CAMS approach emphasizes cooperation between the therapist and patient. “Adolescents are seeking autonomy and independence, and so it’s a good fit philosophically that you would partner alongside the teen as opposed to starting in a more adversarial sort of way – not that we as therapists ever do that. But it can be more tense when suicide is on the table and you feel unprepared,” Dr. Adrian said.

Seattle Children’s Hospital is persuaded enough to make CAMS part of its standard of care, Dr. Adrian said.

CAMS is a framework for patient management that has no prerequisites for the therapeutic approach. “It’s principle driven, not protocol driven. Clinicians can use whatever specific interventions they feel are appropriate for the drivers (of the suicidality). What we’re trying to change is the approach to the suicidal patient, so that it is not an anxiety-provoking, terrifying experience for the clinician – because we know that a suicidal patient is the most anxiety-provoking task for clinicians,” Dr. Adrian said. “We want clinicians to feel prepared and protected in providing the elements of care,” Dr. Adrian said in an interview.

The framework incorporates a suicide-status form (SSF), which assesses theory-driven and epidemiologically guided risk factors and helps to identify the drivers or the reasons why suicide is compelling to the patient. Those drivers then help inform crisis prevention efforts and the selection of interventions.

Three randomized, controlled trials have demonstrated the efficacy of CAMS over standard of care in adult patients, showing that the SSF is an effective assessment tool and that CAMS reduces suicidal ideation and leads to decreases in distress, depression, and hopelessness. There are no randomized, controlled trials showing its efficacy in children, but Seattle Children’s Hospital is conducting a pilot study in 12 youth and have found a 40% response rate at 8 weeks.

The philosophy behind CAMS is to promote collaborative management between the patient and clinician. The SSF gauges the patient’s status and trajectory, while the CAMS therapeutic worksheet helps to distinguish direct and indirect drivers of suicidal behavior. In cases in which trauma symptoms or experiences are tied to suicidal behavior, they receive priority for treatment. The framework provides for discussion of options and treatment choice through collaboration between the clinician and the patient.

The patient and clinician fill out an SSF in the first session and use it to create a crisis convention plan, which includes gaining a commitment to treatment, removing or restricting access to lethal means, and incorporating parental monitoring.

Dr. Adrian is hopeful that the CAMS framework will help health care workers address suicidality in traumatized youth and adolescents. Currently, they may feel intimidated by a stricken child’s issues. “You don’t want to be responsible for a child dying, so you may overrespond with an intervention like an emergency department evaluation or an inpatient hospitalization that may be iatrogenic – there are data coming out from adults that hospitalization contributes to suicide risk above and beyond other risk factors,” Dr. Adrian said.

CAMS is simple and flexible, according to Dr. Adrian, and can be used by psychiatrists, social workers, substance use counselors, and others. At Seattle Children’s Hospital, clinicians have embraced it. “They feel it changes their practice. It gets to the heart of the matter quickly, and they feel more confident having that framework,” Dr. Adrian said.

Dr. Adrian has no conflicts of interest or disclosures.

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

SAN FRANCISCO – A new analysis of cholera strains suggests that bacteriophages – viruses that prey on bacteria – are engaged in an evolutionary arms race with the Vibrio cholerae bacteria, and the dynamic between the two organisms may be an important factor in determining which strain of cholera goes on to cause a pandemic.

CDC

The work, presented by Kim Seed, PhD, at IDWeek, an annual scientific meeting on infectious diseases, examined a defense mechanism in V. cholerae, called phage inducible chromosomal island like element (PLE), as well as a unique mechanism in the bacteriophage to counter it. The work adds insight into the cholera strains that could emerge to produce future epidemics, and could even inform the use of bacteriophages as prophylactic agents to counter V. cholerae infection

In her talk, Dr. Seed described the dynamics of the current cholera pandemic, which is the seventh in recorded history and began in the 1960s. Over the past 100 years, six previous strains arose and then vanished, yielding each time to a new strain that became the predominant cholera-causing agent.

“This pattern of evolution, this so-called disappearing act, drives my research – I’m trying to understand what factors promote the evolution of novel genetic variants, and what factors contribute to why those variants disappear,” said Dr. Seed.

That quest brought her to the Bay of Bengal and Bangladesh. Genetic studies have shown this region to be the epicenter of cholera strains. It appears that cholera strains evolve there and then invade other regions of the world as a result of human travel and activity. Go to places in Africa or Asia where there is a cholera outbreak, and you can find cholera bacteria in the water that has the potential to cause human disease – but it won’t be the strain that is causing disease nearby. “(The culprit) is these introduced strains that come from Southeast Asia,” said Dr. Seed.

So her team went to Bangladesh, and studied cholera bacteria isolated from patients at the International Centre for Diarrhoeal Disease Research. The current strain is antibiotic resistant, as has been well documented. But Dr. Seed was interested in bacteriophages – viruses that prey on bacteria – because they live in the water supply and can also be isolated from the stool of cholera-infected patients, and it seemed likely that they could be an important selective force.

Indeed, her team found only a few bacteriophages that prey on V. cholerae in the samples from this hospital, and one type predominated in samples collected between 2001 and 2017; a bacteriophage known as ICP1. “This set up a very nice dynamic to be able to study the molecular mechanisms by which co-evolution was occurring in this one specific phage and Vibrio cholerae,” said Dr. Seed.

Genetic analysis revealed a mobile genetic element in V. cholerae – PLE –that conferred specific resistance against ICP1. After an infection, one of the bacteriophage’s proteins leads to excision and transcription of PLE. That produces a predicted 25 proteins, which in turn interfere with ICP1 through an as yet undetermined mechanism. But it’s effective, completely shutting down bacteriophage replication.

That couldn’t be the end of the story, Dr. Seed reasoned. Otherwise the bacteriophage would die out entirely for lack of a vulnerable host. More searching revealed the biggest surprise of all – ICP1, even though it is a virus, contains a complete suite of CRISPR (clustered regularly interspaced short palindromic repeats) apparatus that directly targets the PLE sequence. CRISPR is currently all the rage as a potential tool for genetic modification. It was discovered in bacteria, as a sort of immune response against bacteriophages. The CRISPR DNA contains a guide sequence that is complementary to and binds viral DNA, and then recruits other proteins to destroy the viral blueprint.

But here, for the first and only time, Dr. Seed’s team found that a bacteriophage had turned the tables, somehow capturing a CRISPR system of its own and turning it against its host’s defense system. Soon after infection, PLE switches on in response to its bacteriophage trigger, but the ICP1 counters by activating its CRISPR system, which is effective enough to allow the bacteriophage to reproduce.

The researchers then examined historical samples, and found another surprise: The appearance of CRISPR in ICP1 predated the appearance of the PLE variant that it targeted in V. cholerae. A little more digging revealed older variants of PLE, now gone from the V. cholerae population. “This explains why ICP1 had to have CRISPR, so it could overcome these previously prevalent genetic variants,” said Dr. Seed.

All told, the researchers found five unique PLE variants dating back to 1931, and the co-evolution of V. cholerae and ICP1 no doubt stretch much farther into the dim past. More recently, they found that previous strains of V. cholerae that went extinct also had different variations of PLE, suggesting that it may have been a temporary evolutionary victory by ICP1 over a PLE variant that caused the demise of an existing V. cholerae strain. But each time, it seems the bacteria responded with a new PLE variant, prolonging the arms race.

The work has the potential to affect other bacterial diseases, since most bacteria have phages that prey on them. “I have no doubt that they are a strong presence and selective force on all pathogens. People haven’t done so much work on that yet, but I think it’s coming,” said Dr. Seed.

SOURCE: Seed K. et al. ID Week 2018. Abstract 954.

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

Psoriasis patients are more vulnerable to systemic infections, including influenza-related pneumonia, but a new study shows that they are less likely to receive the influenza vaccine than patients with RA.

Jovanmandic/Thinkstock

Vaccination rates were higher in psoriasis patients aged over 50 years, those who were female, and those with other chronic medical conditions, however.

Megan H. Noe, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and her coauthors referred to recent evidence suggesting that psoriasis involves systemic inflammation that increase the risk of comorbidities and that hospitalization rates for serious infections, including lower respiratory tract infections and pneumonia, are higher among adults with psoriasis than those who do not have psoriasis.

To compare influenza vaccination rates in psoriasis patients with those among patients with other chronic diseases, they conducted a cohort study, drawing from administrative and commercial claims data from OptumInsight Clinformatics Data Mart. They examined all adult patients with psoriasis, RA, or chronic hypertension who required oral antihypertensive medication. The study population included individuals tracked during the 2010-2011 flu season and 24 months prior (September 2008 to March 2011). This year was chosen because it was labeled as a “typical” season by the Centers for Disease Control and Prevention.

The primary outcome was a claim for an influenza vaccine, and covariates included age, length of residency, gender, and a clinical history of a range of conditions known to be associated with greater risk of influenza complications.

The population included 17,078 patients with psoriasis, 21,832 with RA, and 496,972 with chronic hypertension. After controlling for sex and age, the probability of getting a flu vaccine was similar between psoriasis and hypertension patients, but RA patients were more likely to be vaccinated than patients with psoriasis (odds ratio, 1.08; 95% confidence interval, 1.03-1.13). But the likelihood varied with age: 30-year-old patients with RA were more likely than a 30-year-old psoriasis patient to get a flu shot (OR, 1.30; 95% CI, 1.18-1.45), while a 70-year-old patient with RA was about as likely to get the flu vaccine as a 70-year-old patient with psoriasis.

Female psoriasis patients were more likely to get a flu shot than males (OR, 1.29; 95% CI, 1.20-1.38). Among the psoriasis patients, having some medical comorbidities were linked to a greater likelihood of being vaccinated, including asthma (OR, 1.58; 95% CI, 1.40-1.77), chronic liver disease (OR, 1.23; 95%, 1.03-1.47), diabetes (OR, 1.48; 95% CI, 1.36-1.63), HIV (OR, 3.68; 95% CI, 2.06-6.57), history of malignancy (OR, 1.21; 95% CI, 1.09-1.34), and psoriatic arthritis (OR, 1.40; 95% CI, 1.25-1.58).

There was no association between the use of an oral systemic therapy or biologic treatment and vaccination rates.

The authors suggested that psoriasis patients, especially younger ones, may not get adequate counseling on the value of the flu vaccine from their physicians. Studies have shown that, among the American public, health care providers are the most influential source of information about the flu vaccine. Among younger patients, the dermatologist may be a psoriasis patient’s primary health care provider, so it is important for dermatologists to counsel patients about the recommended vaccines, the authors wrote.

“Further research understanding why adults with psoriasis do not receive recommended vaccinations will help to create targeted interventions to improve vaccination rates and decrease hospitalizations in adults with psoriasis,” they concluded.

The study relied on administrative claims, so the results may not be generalizable to patients with insurance types other than those in the database or who are uninsured, the authors noted.

This study was funded by the National Psoriasis Foundation, the Dermatology Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Noe and three other authors did not report any disclosures, the fifth author reported multiple disclosures related to various pharmaceutical companies.

SOURCE: Noe MH et al. J Invest Dermatol. 2018 Oct 10. doi: 10.1016/j.jid.2018.09.012.
 

Psoriasis patients are more vulnerable to systemic infections, including influenza-related pneumonia, but a new study shows that they are less likely to receive the influenza vaccine than patients with RA.

Jovanmandic/Thinkstock

Vaccination rates were higher in psoriasis patients aged over 50 years, those who were female, and those with other chronic medical conditions, however.

Megan H. Noe, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and her coauthors referred to recent evidence suggesting that psoriasis involves systemic inflammation that increase the risk of comorbidities and that hospitalization rates for serious infections, including lower respiratory tract infections and pneumonia, are higher among adults with psoriasis than those who do not have psoriasis.

To compare influenza vaccination rates in psoriasis patients with those among patients with other chronic diseases, they conducted a cohort study, drawing from administrative and commercial claims data from OptumInsight Clinformatics Data Mart. They examined all adult patients with psoriasis, RA, or chronic hypertension who required oral antihypertensive medication. The study population included individuals tracked during the 2010-2011 flu season and 24 months prior (September 2008 to March 2011). This year was chosen because it was labeled as a “typical” season by the Centers for Disease Control and Prevention.

The primary outcome was a claim for an influenza vaccine, and covariates included age, length of residency, gender, and a clinical history of a range of conditions known to be associated with greater risk of influenza complications.

The population included 17,078 patients with psoriasis, 21,832 with RA, and 496,972 with chronic hypertension. After controlling for sex and age, the probability of getting a flu vaccine was similar between psoriasis and hypertension patients, but RA patients were more likely to be vaccinated than patients with psoriasis (odds ratio, 1.08; 95% confidence interval, 1.03-1.13). But the likelihood varied with age: 30-year-old patients with RA were more likely than a 30-year-old psoriasis patient to get a flu shot (OR, 1.30; 95% CI, 1.18-1.45), while a 70-year-old patient with RA was about as likely to get the flu vaccine as a 70-year-old patient with psoriasis.

Female psoriasis patients were more likely to get a flu shot than males (OR, 1.29; 95% CI, 1.20-1.38). Among the psoriasis patients, having some medical comorbidities were linked to a greater likelihood of being vaccinated, including asthma (OR, 1.58; 95% CI, 1.40-1.77), chronic liver disease (OR, 1.23; 95%, 1.03-1.47), diabetes (OR, 1.48; 95% CI, 1.36-1.63), HIV (OR, 3.68; 95% CI, 2.06-6.57), history of malignancy (OR, 1.21; 95% CI, 1.09-1.34), and psoriatic arthritis (OR, 1.40; 95% CI, 1.25-1.58).

There was no association between the use of an oral systemic therapy or biologic treatment and vaccination rates.

The authors suggested that psoriasis patients, especially younger ones, may not get adequate counseling on the value of the flu vaccine from their physicians. Studies have shown that, among the American public, health care providers are the most influential source of information about the flu vaccine. Among younger patients, the dermatologist may be a psoriasis patient’s primary health care provider, so it is important for dermatologists to counsel patients about the recommended vaccines, the authors wrote.

“Further research understanding why adults with psoriasis do not receive recommended vaccinations will help to create targeted interventions to improve vaccination rates and decrease hospitalizations in adults with psoriasis,” they concluded.

The study relied on administrative claims, so the results may not be generalizable to patients with insurance types other than those in the database or who are uninsured, the authors noted.

This study was funded by the National Psoriasis Foundation, the Dermatology Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Noe and three other authors did not report any disclosures, the fifth author reported multiple disclosures related to various pharmaceutical companies.

SOURCE: Noe MH et al. J Invest Dermatol. 2018 Oct 10. doi: 10.1016/j.jid.2018.09.012.
 

Psoriasis patients are more vulnerable to systemic infections, including influenza-related pneumonia, but a new study shows that they are less likely to receive the influenza vaccine than patients with RA.

Jovanmandic/Thinkstock

Vaccination rates were higher in psoriasis patients aged over 50 years, those who were female, and those with other chronic medical conditions, however.

Megan H. Noe, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, and her coauthors referred to recent evidence suggesting that psoriasis involves systemic inflammation that increase the risk of comorbidities and that hospitalization rates for serious infections, including lower respiratory tract infections and pneumonia, are higher among adults with psoriasis than those who do not have psoriasis.

To compare influenza vaccination rates in psoriasis patients with those among patients with other chronic diseases, they conducted a cohort study, drawing from administrative and commercial claims data from OptumInsight Clinformatics Data Mart. They examined all adult patients with psoriasis, RA, or chronic hypertension who required oral antihypertensive medication. The study population included individuals tracked during the 2010-2011 flu season and 24 months prior (September 2008 to March 2011). This year was chosen because it was labeled as a “typical” season by the Centers for Disease Control and Prevention.

The primary outcome was a claim for an influenza vaccine, and covariates included age, length of residency, gender, and a clinical history of a range of conditions known to be associated with greater risk of influenza complications.

The population included 17,078 patients with psoriasis, 21,832 with RA, and 496,972 with chronic hypertension. After controlling for sex and age, the probability of getting a flu vaccine was similar between psoriasis and hypertension patients, but RA patients were more likely to be vaccinated than patients with psoriasis (odds ratio, 1.08; 95% confidence interval, 1.03-1.13). But the likelihood varied with age: 30-year-old patients with RA were more likely than a 30-year-old psoriasis patient to get a flu shot (OR, 1.30; 95% CI, 1.18-1.45), while a 70-year-old patient with RA was about as likely to get the flu vaccine as a 70-year-old patient with psoriasis.

Female psoriasis patients were more likely to get a flu shot than males (OR, 1.29; 95% CI, 1.20-1.38). Among the psoriasis patients, having some medical comorbidities were linked to a greater likelihood of being vaccinated, including asthma (OR, 1.58; 95% CI, 1.40-1.77), chronic liver disease (OR, 1.23; 95%, 1.03-1.47), diabetes (OR, 1.48; 95% CI, 1.36-1.63), HIV (OR, 3.68; 95% CI, 2.06-6.57), history of malignancy (OR, 1.21; 95% CI, 1.09-1.34), and psoriatic arthritis (OR, 1.40; 95% CI, 1.25-1.58).

There was no association between the use of an oral systemic therapy or biologic treatment and vaccination rates.

The authors suggested that psoriasis patients, especially younger ones, may not get adequate counseling on the value of the flu vaccine from their physicians. Studies have shown that, among the American public, health care providers are the most influential source of information about the flu vaccine. Among younger patients, the dermatologist may be a psoriasis patient’s primary health care provider, so it is important for dermatologists to counsel patients about the recommended vaccines, the authors wrote.

“Further research understanding why adults with psoriasis do not receive recommended vaccinations will help to create targeted interventions to improve vaccination rates and decrease hospitalizations in adults with psoriasis,” they concluded.

The study relied on administrative claims, so the results may not be generalizable to patients with insurance types other than those in the database or who are uninsured, the authors noted.

This study was funded by the National Psoriasis Foundation, the Dermatology Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Noe and three other authors did not report any disclosures, the fifth author reported multiple disclosures related to various pharmaceutical companies.

SOURCE: Noe MH et al. J Invest Dermatol. 2018 Oct 10. doi: 10.1016/j.jid.2018.09.012.
 

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – In gram-negative bloodstream infections, in patients who are stable at 48 hours, are no longer feverish, and whose infections aren’t invasive, it may be safe to step down from IV antibiotics to oral ciprofloxacin (PO). That is the tentative conclusion from a new single-center, retrospective chart review.

Jim Kling/MDedge News

The study adds to growing suspicion among practitioners that stepping down may be safe in gram-negative patients, as well as mounting evidence that shorter treatment durations may also be safe, according to Gregory Cook, PharmD, who presented the study at a poster session at an annual scientific meeting on infectious diseases. “We’re getting more aggressive” in backing off IV treatment, he said in an interview.

Oral medications are associated with shorter hospital stays and decreased costs.

Froedtert & the Medical College of Wisconsin, where the study was performed, switched some years ago from levofloxacin to ciprofloxacin for cost reasons. But ciprofloxacin has a lower bioavailability, and a recent study showed levofloxacin had less treatment failure at 90 days than ciprofloxacin. Levofloxacin is restricted at the institution and requires antibiotic stewardship approval for use, whereas ciprofloxacin can be used without approval.

But the researchers were concerned about bioavailability. “We like to think of ciprofloxacin as having excellent bioavailability, and it does, it has 80% bioavailability, but it’s still not exactly the same as levofloxacin. We wanted to look into this and see if we were doing our patients a disservice or not (by stepping down to ciprofloxacin),” said Dr. Cook, who is now the antimicrobial stewardship pharmacist at Children’s Hospital New Orleans. The results were reassuring. “Ultimately we were trying to see how our patients were doing on oral ciprofloxacin, and after 2-3 days of IV therapy, most of them did extremely well,” he said. 

The researchers analyzed the records of 198 patients who presented with a monomicrobial, gram-negative bloodstream infection between January 2015 and January 2018, and who survived at least 5 days past blood culture collection. One hundred and three switched to PO within 5 days, while 95 remained on intravenous antibiotics for longer than 5 days. On average, patients in the PO group received IV antibiotics for 2 days, while the IV group averaged 15 days. Oral ciprofloxacin treatment length averaged 12 days.

The primary endpoint of treatment failure at 90 days, defined as recurrent infection or all-cause mortality, favored the PO group (1.9% versus 16.8%, P less than .01). This was likely because of patient selection, as those in the IV group tended to be more ill, according to Dr. Cook. More were immunosuppressed (41% IV versus 22% in PO group, P less than .01). There were more nonurinary sources of infection (41% in IV group, P less than .01; 65% urinary source in PO group). Thirty-four percent of the PO group had an infectious disease consult, compared with 60% of the IV group.

SOURCE: Gregory Cook et al. ID Week 2018. Abstract 39.

SAN FRANCISCO – An adjuvanted trivalent flu vaccine cuts the risk of hospitalizations in nursing home residents by about 6%, according to a new study presented at an annual scientific meeting on infectious diseases.

“It’s one thing to say you have a more immunogenic vaccine, it’s another thing to be able to say it offers clinical benefit, especially in the oldest old and the frailest frail,” says Stefan Gravenstein, MD, professor of medicine and health services, policy and practice at the Brown University School of Public Health, Providence, R.I. Dr. Gravenstein presented a poster outlying a randomized, clinical trial of the Fluad vaccine in nursing homes.

The study randomized the nursing homes so that some facilities would offer Fluad as part of their standard of care. The design helped address the problem of consent. Any clinical trial that requires individual consent would likely exclude many of the frailest patients, leading to an unrepresentative sample. “So if you want to have a generalizable result, you’d like to have it applied to the population the way you would in the real world, so randomizing the nursing homes rather than the people makes a lot of sense,” said Dr. Gravenstein.

Dr. Gravenstein chose to test the vaccine in nursing home residents, hoping to see a signal in a population in which flu complications are more common. “If you can get a difference in a nursing home population, that’s clinically important, that gives you hope that you can see it in all the other populations, too,” he said.

SOURCE: Gravenstein S et al. IDWeek 2018, Abstract 996.

SAN FRANCISCO – An adjuvanted trivalent flu vaccine cuts the risk of hospitalizations in nursing home residents by about 6%, according to a new study presented at an annual scientific meeting on infectious diseases.

“It’s one thing to say you have a more immunogenic vaccine, it’s another thing to be able to say it offers clinical benefit, especially in the oldest old and the frailest frail,” says Stefan Gravenstein, MD, professor of medicine and health services, policy and practice at the Brown University School of Public Health, Providence, R.I. Dr. Gravenstein presented a poster outlying a randomized, clinical trial of the Fluad vaccine in nursing homes.

The study randomized the nursing homes so that some facilities would offer Fluad as part of their standard of care. The design helped address the problem of consent. Any clinical trial that requires individual consent would likely exclude many of the frailest patients, leading to an unrepresentative sample. “So if you want to have a generalizable result, you’d like to have it applied to the population the way you would in the real world, so randomizing the nursing homes rather than the people makes a lot of sense,” said Dr. Gravenstein.

Dr. Gravenstein chose to test the vaccine in nursing home residents, hoping to see a signal in a population in which flu complications are more common. “If you can get a difference in a nursing home population, that’s clinically important, that gives you hope that you can see it in all the other populations, too,” he said.

SOURCE: Gravenstein S et al. IDWeek 2018, Abstract 996.

SAN FRANCISCO – An adjuvanted trivalent flu vaccine cuts the risk of hospitalizations in nursing home residents by about 6%, according to a new study presented at an annual scientific meeting on infectious diseases.

“It’s one thing to say you have a more immunogenic vaccine, it’s another thing to be able to say it offers clinical benefit, especially in the oldest old and the frailest frail,” says Stefan Gravenstein, MD, professor of medicine and health services, policy and practice at the Brown University School of Public Health, Providence, R.I. Dr. Gravenstein presented a poster outlying a randomized, clinical trial of the Fluad vaccine in nursing homes.

The study randomized the nursing homes so that some facilities would offer Fluad as part of their standard of care. The design helped address the problem of consent. Any clinical trial that requires individual consent would likely exclude many of the frailest patients, leading to an unrepresentative sample. “So if you want to have a generalizable result, you’d like to have it applied to the population the way you would in the real world, so randomizing the nursing homes rather than the people makes a lot of sense,” said Dr. Gravenstein.

Dr. Gravenstein chose to test the vaccine in nursing home residents, hoping to see a signal in a population in which flu complications are more common. “If you can get a difference in a nursing home population, that’s clinically important, that gives you hope that you can see it in all the other populations, too,” he said.

SOURCE: Gravenstein S et al. IDWeek 2018, Abstract 996.

SAN FRANCISCO – A heightened loading dose of vancomycin may lead to faster recovery and greater efficacy in Clostridium difficile infections, according to the results of a quasi-experimental study presented at an annual scientific meeting on infectious diseases.

The study looked at a loading dose of 500 mg of vancomycin delivered four times per day for the first 48 hours, followed by a step down to 125 mg every 6 hours. It came on the heels of an attempted randomized, clinical trial that was inconclusive because of insufficient recruitment. Still, the results were promising enough to convince the Yale New Haven Hospital to make it standard practice in C. difficile patients.

Samad Tirmizi, PharmD, an infectious disease pharmacist at Stony Brook University (N.Y.), shares the results of a comparison of outcomes before and after the initiation of this treatment protocol in a video interview.

The approach grew out of concerns that vancomycin may not achieve sufficient concentrations in the colon early in treatment. A pharmacokinetics study published in 2010 suggested that a high initial loading led to higher fecal vancomycin levels, even in patients with increased stool frequency (BMC Infect Dis. 2010 Dec 30;10:363).

SOURCE: Tirmizi S et al. IDWeek 2018, Abstract 1980.

SAN FRANCISCO – A heightened loading dose of vancomycin may lead to faster recovery and greater efficacy in Clostridium difficile infections, according to the results of a quasi-experimental study presented at an annual scientific meeting on infectious diseases.

The study looked at a loading dose of 500 mg of vancomycin delivered four times per day for the first 48 hours, followed by a step down to 125 mg every 6 hours. It came on the heels of an attempted randomized, clinical trial that was inconclusive because of insufficient recruitment. Still, the results were promising enough to convince the Yale New Haven Hospital to make it standard practice in C. difficile patients.

Samad Tirmizi, PharmD, an infectious disease pharmacist at Stony Brook University (N.Y.), shares the results of a comparison of outcomes before and after the initiation of this treatment protocol in a video interview.

The approach grew out of concerns that vancomycin may not achieve sufficient concentrations in the colon early in treatment. A pharmacokinetics study published in 2010 suggested that a high initial loading led to higher fecal vancomycin levels, even in patients with increased stool frequency (BMC Infect Dis. 2010 Dec 30;10:363).

SOURCE: Tirmizi S et al. IDWeek 2018, Abstract 1980.

SAN FRANCISCO – A heightened loading dose of vancomycin may lead to faster recovery and greater efficacy in Clostridium difficile infections, according to the results of a quasi-experimental study presented at an annual scientific meeting on infectious diseases.

The study looked at a loading dose of 500 mg of vancomycin delivered four times per day for the first 48 hours, followed by a step down to 125 mg every 6 hours. It came on the heels of an attempted randomized, clinical trial that was inconclusive because of insufficient recruitment. Still, the results were promising enough to convince the Yale New Haven Hospital to make it standard practice in C. difficile patients.

Samad Tirmizi, PharmD, an infectious disease pharmacist at Stony Brook University (N.Y.), shares the results of a comparison of outcomes before and after the initiation of this treatment protocol in a video interview.

The approach grew out of concerns that vancomycin may not achieve sufficient concentrations in the colon early in treatment. A pharmacokinetics study published in 2010 suggested that a high initial loading led to higher fecal vancomycin levels, even in patients with increased stool frequency (BMC Infect Dis. 2010 Dec 30;10:363).

SOURCE: Tirmizi S et al. IDWeek 2018, Abstract 1980.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

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The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

SAN FRANCISCO – In early October, the Food and Drug Administration approved omadacycline (Nuzyra) for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections in adults.

The drug is a synthetic tetracycline designed to overcome some of the resistance mechanisms that can undermine traditional tetracycline drugs. It gained approval on the strength of the Oasis-1 (NCT03482011) and Oasis-2 (NCT03535194) trials, which demonstrated the drug’s noninferiority to linezolid.

At IDWeek 2018, researchers combined the data from the two pivotal trials to gain more power in some of the secondary endpoints, such as adverse events.

Paul McGovern, MD, vice president of clinical and medical affairs at Paratek, which markets omadacycline, discussed the results of the analysis at an annual scientific meeting on infectious diseases.

Combined, the two studies included 691 patients who received omadacycline and 689 who received linezolid. The two drugs achieved similar results for early clinical response, defined as at least a 20% reduction in lesion size 48-72 hours after the first dose. The mean reduction in baseline lesion area at day 3 was 53.4% in the omadacycline group and 53.0% in the linezolid group. At the end of the treatment period, those values were 93.9% and 93.7%, respectively, Dr. McGovern reported.

A total of 28.5% of patients receiving omadacycline reported drug-related treatment-emergent adverse events, compared with 16.1% of the linezolid group. The omadacycline group experienced higher frequency of nausea (21.9% vs. 8.7%) and vomiting (11.4% vs. 3.9%), he said.

The Oasis 1 and Oasis 2 studies were funded by Paratek. Dr. McGovern is an employee of Paratek.

SOURCE: McGovern P et al. IDWeek 2018, poster abstract 1347.

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.

SAN FRANCISCO – For the first time, the World Health Organization’s Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI) protocol is being field tested in the Democratic Republic of Congo (DRC), where four different therapeutics are being delivered to Ebola patients. MEURI was created after controversy surrounding the 2014-2016 Ebola outbreak in West Africa, which ultimately led to the decision to integrate research into outbreak responses.

gl0ck/Thinkstock

MEURI is broadly designed for pathogens that have no proven intervention, on the premise that in a disease with high mortality, it can be ethically appropriate to provide experimental therapies during a response, as long as a set of criteria are met that ensure patient autonomy and give patients a reasonable opportunity to improve their condition.

The original plan was to employ experimental drugs under the MEURI umbrella during an Ebola outbreak in the DRC that began in May, but an effective response contained it so quickly that the program was canceled. However, when another Ebola outbreak occurred on Aug. 27, the material was still in the country and ready to be deployed. “That made it very easy to begin using them,” said Elizabeth Higgs, MD, global health science advisor for the division of clinical research at the National Institute for Allergy and Infectious Disease.

Dr. Higgs spoke about the developments during a late-breakers session at IDWeek 2018, an annual scientific meeting on infectious disease.

The therapies under consideration are Zmapp (Leaf Biopharmaceutical), which includes three chimeric monoclonal antibodies that target the main surface protein of the Ebola virus; mAb114 (NIAID), which was isolated in 1995 from a human survivor of Ebola and binds to the core of the Ebola surface protein; Remdesivir (Gilead), a small molecule that is believed to interfere with viral replication; and Regeneron’s Ebola triple monoclonal antibody cocktail, which also targets the surface protein.

Through Oct. 2, 43 Ebola patients have received one of the four drugs: 19 are cured and have been discharged, 12 have died, and 12 are still in recovery. Dr. Higgs cautioned against reading anything into those numbers, however, since no randomization was involved.

Although compassionate use is the primary aim of MEURI, it may be lead to some scientific benefit. The most that can be hoped for is to glean some insight into the safety of the interventions, although even that information is limited. “A colleague and I were talking about this the other day. After the first X number of patients, they were all still alive. What can you say from that? I think what you can say is that it didn’t kill them,” Dr. Higgs said.

Still, researchers are collecting laboratory data from patients to monitor their responses. “With Remdesivir we’re closely examining their transaminase, for example, so I think it will be helpful,” said Dr. Higgs.

SOURCE: Higgs E et al. IDWeek 2018.