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Glucocorticoids plus tofacitinib may boost herpes zoster risk
Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.
Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.
However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.
Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.
The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.
“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.
“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.
The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.
The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.
SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.
Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.
Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.
However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.
Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.
The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.
“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.
“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.
The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.
The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.
SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.
Concomitant use of glucocorticoids with tofacitinib in rheumatoid arthritis may double the risk of herpes zoster, but methotrexate does not appear to increase the risk, outcomes from a cohort study of 8,030 rheumatoid arthritis patients – including 222 cases of herpes zoster – suggest.
Using information from Medicare and MarketScan, researchers found that dual therapy with tofacitinib and glucocorticoids was associated with a 96% increase in the risk of herpes zoster, compared with monotherapy with the Janus kinase inhibitor tofacitinib (95% confidence interval, 33%-188%). The crude incidence rate in those taking concomitant tofacitinib and glucocorticoids was 6 cases per 100 patient-years, compared with an incidence rate of 3.4 cases per 100 patient-years with tofacitinib monotherapy.
However, the addition of methotrexate therapy to tofacitinib was not associated with an increased risk of herpes zoster, and the incidence rate in patients on this dual therapy was 3.7 cases per 100 patient-years, Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham and his coauthors reported in Arthritis Care & Research.
Women – who constituted 80% of the study population – showed a significantly increased risk of herpes zoster, as did older patients.
The study also found that individuals who had received the live herpes zoster vaccine showed a trend toward a decrease in risk.
“We saw a strong trend for decreased risk related to vaccination with the live agent (Zostavax); the concern with this form of vaccination is that any live vaccination is potentially dangerous in patients receiving potent immunosuppression,” Dr. Curtis and his associates wrote.
“The risks for disease flare, and potentially problematic tolerability related to a relatively high incidence of grade 3 (severe) systemic reactogenicity, may limit enthusiasm until specific data in an RA population is available,” they wrote. However, they noted that a randomized, controlled trial of the live virus vaccine was underway in patients with rheumatoid arthritis who were being treated with tumor necrosis factor inhibitors and suggested that vaccination should be considered in at-risk patients who didn’t have contraindications.
The authors noted that the effect of glucocorticoid exposure on herpes zoster risk in patients taking tofacitinib was similar to that seen in rheumatoid arthritis patients receiving conventional synthetic disease-modifying antirheumatic drugs or biologic therapies.
The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.
SOURCE: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.
FROM ARTHRITIS CARE & RESEARCH
Key clinical point: Patients treated with concomitant glucocorticoids and tofacitinib showed increased risk of herpes zoster.
Major finding: Concomitant use of glucocorticoids and tofacitinib is associated with nearly twofold increase in the risk of herpes zoster.
Study details: Cohort study using data from 8,030 rheumatoid arthritis patients.
Disclosures: The study was partly funded by the Patient-Centered Outcomes Research Institute. Two authors declared research grants and other funding from the pharmaceutical industry, but no other conflicts of interest were declared.
Source: Curtis J et al. Arthritis Care Res. 2018 Oct 8. doi: 10.1002/acr.23769.
TB vaccine shows promise in previously infected
san francisco – A new 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.
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 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.
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 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.
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
REPORTING FROM IDWEEK 2018
Key clinical point: The vaccine is the first to show efficacy in patients previously exposed to the TB bacterium.
Major finding: The vaccine had a protective efficacy of 54%.
Study details: Randomized, controlled trial with 3,330 participants.
Disclosures: 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.
Mysterious polio-like illness baffles medical experts while frightening parents
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
A spike in the number of children with a rare neurological disease that causes polio-like symptoms has health officials across the country scrambling to understand the illness. Yet, more than 4 years after health officials first recorded the most recent uptick in cases, much about the national outbreak remains a mystery.
Acute flaccid myelitis (AFM) affects the gray matter in the spinal cord, causing sudden muscle weakness and a loss of reflexes. The illness can lead to serious complications – including paralysis or respiratory failure – and requires immediate medical attention.
The Centers for Disease Control and Prevention is investigating 127 cases of possible AFM, including 62 that have been confirmed in 22 states this year. At least 90% of the cases are among patients 18 years old and younger. The average age of a patient is 4 years old.
AFM remains extremely rare, even with the recent increase. The CDC estimates fewer than 1 in a million Americans will get the disease. Officials advised parents not to panic but remain vigilant for any sudden onset of symptoms. They also suggested that children stay up to date with their vaccines and practice good hand washing habits.
This year’s outbreak marks the third spike of AFM in 4 years. From August 2014 to September 2018, 386 cases have been confirmed. Yet, experts still do not understand crucial aspects of the disease, including its origins and who is most at risk.
“There is a lot we don’t know about AFM,” said Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases. Here’s what puzzles health officials about AFM:
The cause is still unknown
Acute flaccid myelitis can be caused by viruses, such as polio or West Nile. But federal officials said that those viruses have not been linked to the U.S. outbreak over the past 4 years. They have not isolated the cause of these cases.
Despite symptoms reminiscent of polio, no AFM cases have tested positive for that virus, according to the CDC. Investigators have also ruled out a variety of germs. Environmental agents, viruses, and other pathogens are still being considered.
The 2014 outbreak of AFM coincided with a surge of another virus that caused severe respiratory problems, called EV-D68. However, the CDC could not establish a causal link between AFM and the virus. Since then, no large outbreaks of the virus have occurred, according to the CDC.
Carlos Pardo-Villamizar, MD, a neurologist and director of the Johns Hopkins Transverse Myelitis Center, said that the mystery lies in whether the damage seen in AFM is caused by an external agent or the body’s own defenses.
“At this moment, we don’t know if it’s a virus that is coming and producing direct damage of the gray matter in the spinal cord,” he said, “or if a virus is triggering immunological responses that produce a secondary damage in the spinal cord.”
It’s not clear who is at risk
Although the disease appears to target a certain age group, federal disease experts do not know who is likely to get acute flaccid myelitis.
Dr. Pardo-Villamizar said identifying vulnerable populations is “a work in progress.”
Mary Anne Jackson, MD, a pediatric infectious disease specialist and interim dean of the school of medicine at the University of Missouri–Kansas City, said many of the patients she saw were healthy children before falling ill with the disease. She suspects that a host of factors play a role in the likelihood of getting AFM, but more cases must be reviewed in order to find an answer.
The long-term effects are unknown
The CDC said it doesn’t know how long symptoms of the disease will last for patients. However, experts say that initial indications from a small number of cases suggest a grim outlook.
A study published last year found six of eight children in Colorado with acute flaccid myelitis still struggled with motor skills 1 year after their diagnosis. Nonetheless, the researchers found that the patients and families “demonstrated a high degree of resilience and recovery.”
“The majority of these patients are left with extensive problems,” said Dr. Pardo-Villamizar, who was not involved in the study.
Dr. Jackson, who also saw persistent muscle weakness in her patients, said she believes the CDC may be hesitant to specify the long-term effects of the disease because existing studies have included only small numbers of patients. More studies that include a larger proportion of confirmed cases are needed to better understand long-term outcomes, she said.
KHN’s coverage of children’s health care issues is supported in part by the Heising-Simons Foundation. Kaiser Health News is a nonprofit national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation that is not affiliated with Kaiser Permanente.
How much more proof do you need?
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.
One piece of wisdom I was given in medical school was to never be the first nor the last to adopt a new treatment. The history of medicine is full of new discoveries that don’t work out as well as the first report. It also is full of long standing dogmas that later were proven false. This balancing act is part of being a professional and being an advocate for your patient. There is science behind this art. Everett Rogers identified innovators, early adopters, and laggards as new ideas are diffused into practice.1
A 2007 French study2 that investigated oral amoxicillin for early-onset group B streptococcal (GBS) disease is one of the few times in the past 3 decades in which I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis like American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by full term neonates, even mildly sick ones. It does adequately cross the blood-brain barrier. The French researchers measured serum levels and proved all this using both scientific principles and through a clinical trial.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician to be early adopters. I expected the Red Book would update its recommendations. That didn’t happen.
Meanwhile, I have seen other babies kept for 10 days in the hospital for IV therapy with resultant wasted costs (about $20 million/year in the United States) and income loss for the parents. I’ve treated complications and readmissions caused by peripherally inserted central catheter (PICC) line issues. One baby at home got a syringe of gentamicin given as an IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Because late-onset GBS can be acquired environmentally, there always will be recurrences. Unless you are practicing defensive medicine, the issue isn’t the rate of recurrence; it is whether the more invasive intervention of prolonged IV therapy reduces that rate. Then balance any measured reduction (which apparently is zero) against the adverse effects of the invasive intervention, such as PICC line infections. This Bayesian decision making is hard for some risk-averse humans to assimilate. (I’m part Borg.)
Coon et al.3 have confirmed, using big data, that prolonged IV therapy of uncomplicated, late-onset GBS bacteremia does not generate a clinically significant benefit. It certainly is possible to sow doubt by asking for proof in a variety of subpopulations. Even in the era of intrapartum antibiotic prophylaxis, which has halved the incidence of GBS disease, GBS disease occurs in about 2,000 babies per year in the United States. However, most are treated in community hospitals and are not included in the database used in this new report. With fewer than 2-3 cases of GBS bacteremia per year per hospital, a multicenter, randomized controlled trial would be an unprecedented undertaking, is ethically problematic, and is not realistically happening soon. So these observational data, skillfully acquired and analyzed, are and will remain the best available data.
This new article is in the context of multiple articles over the past decade that have disproven the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Coon et al. show that, by 2015, 5 of 49 children’s hospitals (10%) were early adopters and had already made the switch to mostly using short treatment courses for uncomplicated GBS bacteremia; 14 of 49 (29%) hadn’t changed at all from the obsolete Red Book recommendation. Given this new analysis, what are you laggards4 waiting for?
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. “Diffusion of Innovations,” 5th ed. (New York: Free Press, 2003).
2. Eur J Clin Pharmacol. 2007 Jul;63(7):657-62.
3. Pediatrics. 2018;142(5):e20180345.
4. https://en.wikipedia.org/wiki/Diffusion_of_innovations.
Stepdown to oral ciprofloxacin looks safe in gram-negative bloodstream infections
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.
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.
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.
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.
REPORTING FROM IDWEEK 2018
Key clinical point: Stepping down to oral ciprofloxacin at 48 hours is likely safe in stable patients.
Major finding: The 90-day treatment failure rate was 1.9% in patients switched to oral ciprofloxacin.
Study details: Retrospective analysis of 193 cases.
Disclosures: The study was not funded. Dr. Cook declared no financial conflicts of interest.
Source: ID Week 2018. Abstract 39.
In C. difficile, metronidazole may not benefit ICU patients on vancomycin
SAN FRANCISCO – , according to a review of 101 cases at the University of Maryland.
Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.
“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.
“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”
The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).
The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.
Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).
The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.
The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).
Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.
The mean age in the study was about 60 years old, and just over half of the subjects were men.
Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.
There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.
SOURCE: Vega AD et al. ID Week 2018, Abstract 488.
SAN FRANCISCO – , according to a review of 101 cases at the University of Maryland.
Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.
“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.
“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”
The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).
The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.
Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).
The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.
The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).
Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.
The mean age in the study was about 60 years old, and just over half of the subjects were men.
Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.
There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.
SOURCE: Vega AD et al. ID Week 2018, Abstract 488.
SAN FRANCISCO – , according to a review of 101 cases at the University of Maryland.
Adding metronidazole is a common move in ICUs when patients start circling the drain with C. difficile, in part because delivery to the gut doesn’t depend on gut motility. “At that point, you are throwing the kitchen sink at them, but it’s” based, like much in C. difficile management, on expert opinion, not evidence, said study lead Ana Vega, PharmD, a former resident at the university’s school of pharmacy in Baltimore, and now an infectious disease pharmacist at Jackson Memorial Hospital, Miami. The investigators wanted to plug the evidence gap. Forty-seven of the 101 patients in their review – all with signs of C. difficile sepsis – had IV metronidazole added to their vancomycin regimens. Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm, and not significantly different (P = .338). There were also no significant differences in resolution rates or normalization of white blood cell counts and temperature.
“Our data question the utility of” of adding IV metronidazole to oral vancomycin in patients with severe disease. “It’s definitely something to think twice about because metronidazole isn’t benign. It makes people feel crummy; you can induce resistance; and it increases the risk of vancomycin-resistant Enterococci colonization,” already a risk with vancomycin, Dr. Vega said at an annual scientific meeting on infectious diseases.
“When you get to the point that you are trying combination therapy based on expert opinion, I think fecal transplants are something to consider” because the success rates are so high. “That would be my suggestion,” she said, even though “it’s much easier to write an order for a drug than to get a fecal transplant.”
The issue is far from resolved, and debate will continue. A similar review of ICU patients at Wake Forest University in Winston-Salem, N.C., did find a significant mortality benefit with combination therapy, regardless of C. difficile severity (Clin Infect Dis. 2015 Sep 15. doi: 10.1093/cid/civ409).
The Maryland investigators excluded patients with toxic megacolon and other life-threatening intra-abdominal complications requiring surgery, because combination therapy is more strongly recommended in fulminant disease. They were interested in people who were not quite ready for the operating room, when what to do is more in doubt.
Subjects were admitted to the ICU from April 2016 to April 2018 with positive C. difficile nucleic acid testing and an order for oral vancomycin. The only statistically significant baseline differences were that patients who got IV metronidazole had higher median white blood cell counts (18,400 versus 13,900 cells/mL; P = .035) and were more likely to receive higher than 500-mg doses of vancomycin (36.2% versus 7.4%; P less than .0001).
The Mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the combination group was 23 versus 19 in the monotherapy arm (P = .247). There was no difference in the probability of receiving metronidazole based on the score.
The study again found no significant 30-day mortality differences among 76 patients matched by their APACHE II scores (15.8% in the combination arm versus 9.7%; P = .480).
Severe C. difficile infection was defined as either a white cell count above 15,000 or below 4,000 cells/mL, or a serum creatinine at least 1.5 times above baseline, plus at least one other sign of severe sepsis, such as a mean arterial pressure at or below 60 mm Hg. Metronidazole was started within 72 hours of the first vancomycin dose, and subjects on combination therapy were on both for at least 72 hours.
The mean age in the study was about 60 years old, and just over half of the subjects were men.
Dr. Vega said the investigators hope to expand their sample size and see if patients with more virulent strains of C. difficile do better on combination therapy.
There was no industry funding for the work, and the investigators didn’t have any relevant disclosures.
SOURCE: Vega AD et al. ID Week 2018, Abstract 488.
REPORTING FROM ID WEEK 2018
Key clinical point: The jury is still out on whether adding IV metronidazole helps C. difficile patients already on oral vancomycin in the ICU. Consider fecal transplant.
Major finding: Thirty-day mortality was 14.9% in the combination group versus 7.4% in the monotherapy arm (P = .338).
Study details: Review of 101 ICU patients with severe C. difficile infections
Disclosures: There was no industry funding for the work, and the investigators didn’t have any disclosures.
Source: Vega AD. ID Week 2018, Abstract 488.
Need blood STAT? Call for a drone
BOSTON – While Amazon and other retailers are experimenting with drones to deliver toasters and toilet seats to your doorstep, drone-delivered platelets and fresh frozen plasma may be coming soon to a hospital near you, experts said at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.
“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries – that’s almost 20,000 units of blood,” he said.
One-third of all deliveries are needed for urgent, life-saving interventions, he said.
The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, Mr. Kenney said.
Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, however, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, said Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.
Dr. Eastvold, who is also a private pilot, described the regulatory hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters are currently. He added, however, “I can guarantee you that in the future this is going to be an applicable technology to our industry in one way, shape, or another.”
Fast and cheap
Speed and cost are two of the most compelling arguments for blood banks to use drones. Mr. Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section. The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.
They placed an order for more blood products – ordering can be done by text message or via WhatsApp, a free, cross-platform messaging and voiceover IP calling service – and over the course of 90 minutes Zipline was able to deliver, using multiple drone launches, 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.
Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15-25 minutes by air, Mr. Kenney said.
The drones – more formally known as “unmanned aerial vehicles” (UAVs) – fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters and drop the package, which has a parachute attached. Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Mr. Kenney said.
“The whole process is 100% autonomous. The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package,” he explained.
As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.
Airborne deliveries are also significantly cheaper than ground-based services for local delivery, Dr. Eastvold noted. He cited a study showing that the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more, drones could be as cheap as 5 cents per mile with delivery within about 30 minutes, he said.
The fly in the ointment
Dr. Eastvold outlined the significant barriers to adoption of drone-based delivery systems in the United States, ranging from differences in state laws about when, where, and how drones can be used and who can operate them, to Federal Aviation Administration airspace restrictions and regulations.
For example, the FAA currently requires “line-of-sight” operation only for most drone operators, meaning that the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.
In addition, federal regulations require commercial drone pilots to be 16 years old or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.
Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery. In 2017, they demonstrated that a drone could successfully deliver human blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.
Mr. Kenney said that his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.
BOSTON – While Amazon and other retailers are experimenting with drones to deliver toasters and toilet seats to your doorstep, drone-delivered platelets and fresh frozen plasma may be coming soon to a hospital near you, experts said at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.
“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries – that’s almost 20,000 units of blood,” he said.
One-third of all deliveries are needed for urgent, life-saving interventions, he said.
The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, Mr. Kenney said.
Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, however, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, said Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.
Dr. Eastvold, who is also a private pilot, described the regulatory hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters are currently. He added, however, “I can guarantee you that in the future this is going to be an applicable technology to our industry in one way, shape, or another.”
Fast and cheap
Speed and cost are two of the most compelling arguments for blood banks to use drones. Mr. Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section. The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.
They placed an order for more blood products – ordering can be done by text message or via WhatsApp, a free, cross-platform messaging and voiceover IP calling service – and over the course of 90 minutes Zipline was able to deliver, using multiple drone launches, 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.
Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15-25 minutes by air, Mr. Kenney said.
The drones – more formally known as “unmanned aerial vehicles” (UAVs) – fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters and drop the package, which has a parachute attached. Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Mr. Kenney said.
“The whole process is 100% autonomous. The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package,” he explained.
As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.
Airborne deliveries are also significantly cheaper than ground-based services for local delivery, Dr. Eastvold noted. He cited a study showing that the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more, drones could be as cheap as 5 cents per mile with delivery within about 30 minutes, he said.
The fly in the ointment
Dr. Eastvold outlined the significant barriers to adoption of drone-based delivery systems in the United States, ranging from differences in state laws about when, where, and how drones can be used and who can operate them, to Federal Aviation Administration airspace restrictions and regulations.
For example, the FAA currently requires “line-of-sight” operation only for most drone operators, meaning that the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.
In addition, federal regulations require commercial drone pilots to be 16 years old or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.
Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery. In 2017, they demonstrated that a drone could successfully deliver human blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.
Mr. Kenney said that his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.
BOSTON – While Amazon and other retailers are experimenting with drones to deliver toasters and toilet seats to your doorstep, drone-delivered platelets and fresh frozen plasma may be coming soon to a hospital near you, experts said at AABB 2018, the annual meeting of the group formerly known as the American Association of Blood Banks.
Using a system of completely autonomous delivery drones launched from a central location, U.S.-based Zipline International delivers blood products to treat postpartum hemorrhage, trauma, malaria, and other life-threatening conditions to patients in rural Rwanda, according to company spokesman Chris Kenney.
“In less than 2 years in Rwanda, we’ve made almost 10,000 deliveries – that’s almost 20,000 units of blood,” he said.
One-third of all deliveries are needed for urgent, life-saving interventions, he said.
The system, which delivers 30% of all blood products used in Rwanda outside the capital Kigali, has resulted in 100% availability of blood products when needed, a 98% reduction in waste (i.e., when unused blood products are discarded because of age), and a 175% increase in the use of platelets and fresh frozen plasma, Mr. Kenney said.
Setting up an airborne delivery network in the largely unregulated and uncrowded Rwandan airspace was a relatively simple process, however, compared with the myriad challenges of establishing a similar system for deliveries to urban medical centers in Boston, Chicago, New York, or Los Angeles, said Paul Eastvold, MD, chief medical officer at Vitalant, a nonprofit network of community blood banks headquartered in Spokane, Wash.
Dr. Eastvold, who is also a private pilot, described the regulatory hurdles that will need to be surmounted before blood-delivery drones are as common a sight as traffic helicopters are currently. He added, however, “I can guarantee you that in the future this is going to be an applicable technology to our industry in one way, shape, or another.”
Fast and cheap
Speed and cost are two of the most compelling arguments for blood banks to use drones. Mr. Kenney described the case of a 24-year-old Rwandan woman who had uncontrolled bleeding from complications following a cesarean section. The clinicians treating her opted to give her an immediate red blood cell transfusion, but she continued to bleed, and the hospital ran out of red blood cells in about 15 minutes.
They placed an order for more blood products – ordering can be done by text message or via WhatsApp, a free, cross-platform messaging and voiceover IP calling service – and over the course of 90 minutes Zipline was able to deliver, using multiple drone launches, 7 units of red blood cells, 4 units of plasma, and 2 units of platelets, all of which were transfused into the patient and allowed her condition to stabilize.
Deliveries that would take a minimum of 3 hours by road can be accomplished in about 15-25 minutes by air, Mr. Kenney said.
The drones – more formally known as “unmanned aerial vehicles” (UAVs) – fly a loop starting at the distribution center, find their target, descend to a height of about 10 meters and drop the package, which has a parachute attached. Packages can be delivered within a drop zone the size of two parking spaces, even in gale-force winds, Mr. Kenney said.
“The whole process is 100% autonomous. The aircraft knows where it’s going, it knows what conditions [are], it knows what its payload characteristics are and flies to the delivery point and drops its package,” he explained.
As drones return to the distribution center, they are snared from the air with a wire that catches a small tail hook on the fuselage.
Airborne deliveries are also significantly cheaper than ground-based services for local delivery, Dr. Eastvold noted. He cited a study showing that the cost of ground shipping from a local warehouse by carriers such as UPS or FedEx could be $6 or more, drones could be as cheap as 5 cents per mile with delivery within about 30 minutes, he said.
The fly in the ointment
Dr. Eastvold outlined the significant barriers to adoption of drone-based delivery systems in the United States, ranging from differences in state laws about when, where, and how drones can be used and who can operate them, to Federal Aviation Administration airspace restrictions and regulations.
For example, the FAA currently requires “line-of-sight” operation only for most drone operators, meaning that the operator must have visual contact with the drone at all times. The FAA will, however, grant waivers to individual operators for specified flying conditions on a case-by-case basis, if compelling need or extenuating circumstances can be satisfactorily explained.
In addition, federal regulations require commercial drone pilots to be 16 years old or older, be fluent in English, be in a physical and mental condition that would not interfere with safe operation of a drone, pass an aeronautical knowledge exam at an FAA-approved testing center, and undergo a Transportation Safety Administration background security screening.
Despite these challenges, at least one U.S. medical center, Johns Hopkins University, is testing the use of drones for blood delivery. In 2017, they demonstrated that a drone could successfully deliver human blood samples in temperature-controlled conditions across 161 miles of Arizona desert, in a flight lasting 3 hours.
Mr. Kenney said that his company is developing a second distribution center in Rwanda that will expand coverage to the entire country and is also working with the FAA, federal regulators, and the state of North Carolina to develop a drone-based blood delivery system in the United States.
AT AABB 2018
Novel recombinant vaccine protects animals from Lassa fever
An inactivated recombinant Lassa virus (LASV) and rabies vaccine candidate was developed that protects both mice and guinea pigs from Lassa fever. The vaccine also elicits a lasting humoral response against both LASV and rabies virus in both animal models. The novel vaccine, which uses a rabies virus–derived vector, expresses a codon-optimized LASV glycoprotein, according to Tiago Abreu Mota, a doctoral student at Jefferson University, Philadelphia, and his colleagues.
Lassa fever, a World Health Organization priority disease with a biosafety level of 4, is a hemorrhagic fever caused by the Lassa virus, which has no approved vaccine or potent antiviral treatment, according to the report published online in Nature Communications. So the development of a vaccine would be an important step in protecting the West African population from this deadly disease, which infects an estimated 100,000-300,000 people annually. As many as 80% of Lassa fever exposures are mildly symptomatic and thus go unreported; however, the case fatality rate of full-blown Lassa fever has been reported to reach as high as 50%, according to Mr. Mota and his colleagues.
An advantage to the new vaccine is that it is inactivated and thus could potentially be used in pregnant women and immunosuppressed patients, both of which are major risk groups for Lassa fever, according to the researchers. The vaccine could also protect against rabies, which is another major health concern in the regions affected by the Lassa virus.
In terms of mechanism of action, the vaccine did not induce virus-neutralizing antibodies, but rather appeared to trigger cell-mediated protection through activating natural killer cells to promote significantly more killing of virus-infected cells than nontriggered NK cells (P less than .01), as seen through in vitro testing.
The ability to assay for this form of vaccine effectiveness was a key development, according to the researchers. “The neutralizing antibody has been something of a gold standard in vaccine development. High levels are usually a good indication that the immune reaction is strong enough to deflect viral disease. In the case of Lassa virus, however, neutralizing antibodies have not been very good surrogates, since they are produced in much lower quantities. ... The new surrogate of protection will aid in the development of a more potent vaccine against Lassa virus,” according to a press release by Jefferson University.
This work was supported by various grants from the National Institutes of Health. Mr. Mota and two of his colleagues are inventors on a U.S. provisional patent application for a recombinant Lassa-rabies vaccine.
SOURCE: Mota TA et al. Nat Commun. 2018;9:4223. doi: 10.1038/s41467-018-06741-w.
An inactivated recombinant Lassa virus (LASV) and rabies vaccine candidate was developed that protects both mice and guinea pigs from Lassa fever. The vaccine also elicits a lasting humoral response against both LASV and rabies virus in both animal models. The novel vaccine, which uses a rabies virus–derived vector, expresses a codon-optimized LASV glycoprotein, according to Tiago Abreu Mota, a doctoral student at Jefferson University, Philadelphia, and his colleagues.
Lassa fever, a World Health Organization priority disease with a biosafety level of 4, is a hemorrhagic fever caused by the Lassa virus, which has no approved vaccine or potent antiviral treatment, according to the report published online in Nature Communications. So the development of a vaccine would be an important step in protecting the West African population from this deadly disease, which infects an estimated 100,000-300,000 people annually. As many as 80% of Lassa fever exposures are mildly symptomatic and thus go unreported; however, the case fatality rate of full-blown Lassa fever has been reported to reach as high as 50%, according to Mr. Mota and his colleagues.
An advantage to the new vaccine is that it is inactivated and thus could potentially be used in pregnant women and immunosuppressed patients, both of which are major risk groups for Lassa fever, according to the researchers. The vaccine could also protect against rabies, which is another major health concern in the regions affected by the Lassa virus.
In terms of mechanism of action, the vaccine did not induce virus-neutralizing antibodies, but rather appeared to trigger cell-mediated protection through activating natural killer cells to promote significantly more killing of virus-infected cells than nontriggered NK cells (P less than .01), as seen through in vitro testing.
The ability to assay for this form of vaccine effectiveness was a key development, according to the researchers. “The neutralizing antibody has been something of a gold standard in vaccine development. High levels are usually a good indication that the immune reaction is strong enough to deflect viral disease. In the case of Lassa virus, however, neutralizing antibodies have not been very good surrogates, since they are produced in much lower quantities. ... The new surrogate of protection will aid in the development of a more potent vaccine against Lassa virus,” according to a press release by Jefferson University.
This work was supported by various grants from the National Institutes of Health. Mr. Mota and two of his colleagues are inventors on a U.S. provisional patent application for a recombinant Lassa-rabies vaccine.
SOURCE: Mota TA et al. Nat Commun. 2018;9:4223. doi: 10.1038/s41467-018-06741-w.
An inactivated recombinant Lassa virus (LASV) and rabies vaccine candidate was developed that protects both mice and guinea pigs from Lassa fever. The vaccine also elicits a lasting humoral response against both LASV and rabies virus in both animal models. The novel vaccine, which uses a rabies virus–derived vector, expresses a codon-optimized LASV glycoprotein, according to Tiago Abreu Mota, a doctoral student at Jefferson University, Philadelphia, and his colleagues.
Lassa fever, a World Health Organization priority disease with a biosafety level of 4, is a hemorrhagic fever caused by the Lassa virus, which has no approved vaccine or potent antiviral treatment, according to the report published online in Nature Communications. So the development of a vaccine would be an important step in protecting the West African population from this deadly disease, which infects an estimated 100,000-300,000 people annually. As many as 80% of Lassa fever exposures are mildly symptomatic and thus go unreported; however, the case fatality rate of full-blown Lassa fever has been reported to reach as high as 50%, according to Mr. Mota and his colleagues.
An advantage to the new vaccine is that it is inactivated and thus could potentially be used in pregnant women and immunosuppressed patients, both of which are major risk groups for Lassa fever, according to the researchers. The vaccine could also protect against rabies, which is another major health concern in the regions affected by the Lassa virus.
In terms of mechanism of action, the vaccine did not induce virus-neutralizing antibodies, but rather appeared to trigger cell-mediated protection through activating natural killer cells to promote significantly more killing of virus-infected cells than nontriggered NK cells (P less than .01), as seen through in vitro testing.
The ability to assay for this form of vaccine effectiveness was a key development, according to the researchers. “The neutralizing antibody has been something of a gold standard in vaccine development. High levels are usually a good indication that the immune reaction is strong enough to deflect viral disease. In the case of Lassa virus, however, neutralizing antibodies have not been very good surrogates, since they are produced in much lower quantities. ... The new surrogate of protection will aid in the development of a more potent vaccine against Lassa virus,” according to a press release by Jefferson University.
This work was supported by various grants from the National Institutes of Health. Mr. Mota and two of his colleagues are inventors on a U.S. provisional patent application for a recombinant Lassa-rabies vaccine.
SOURCE: Mota TA et al. Nat Commun. 2018;9:4223. doi: 10.1038/s41467-018-06741-w.
FROM NATURE COMMUNICATIONS
Key clinical point: A novel recombinant Lassa virus vaccine protected guinea pigs and mice against Lassa fever.
Major finding: A novel recombinant Lassa virus vaccine elicited strong humeral antibody response in guinea pigs and mice against Lassa and rabies viruses.
Study details: Animal models and an in vitro cellular system were used to assay for the effectiveness of a novel Lassa fever vaccine.
Disclosures: This work was supported by grants from the National Institutes of Health. Mr. Mota and two of his colleagues are inventors on a U.S. provisional patent application for a recombinant Lassa-rabies vaccine.
Source: Mota TA et al. Nat Commun. 2018;9:4223. doi: 10.1038/s41467-018-06741-w.
Group B strep: Short-course IV controls infant infection
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
The 2007 French study investigating oral amoxicillin for early-onset group B streptococcus is one of the few times in the past 3 decades where I changed my practice based on a single article. It was a large, conclusive study with 222 patients, so it doesn’t need a meta-analysis in the way American research often requires. The research showed that most of what I had been taught about oral amoxicillin was false. Amoxicillin is absorbed well even at doses above 50 mg/kg per day. It is absorbed reliably by neonates, even mildly sick ones. It crosses the blood-brain barrier adequately. The French researchers measured serum levels and proved all this using scientific principles as well as clinical trials.
I have used this oral protocol (10 days total after 2-3 days IV therapy) on two occasions to treat GBS sepsis when I had informed consent of the parents and buy-in from the primary care pediatrician. I waited for the Red Book to update its recommendations. That didn’t happen.
Meanwhile, I saw other babies kept for 10 days in the hospital for IV therapy, with resultant wasted costs and income loss for the parents. I’ve treated complications and readmissions due to PICC line issues. One baby at home got a syringe of gentamicin given IV push instead of a normal saline flush. Mistakes happen at home and in the hospital.
Since late-onset GBS can be acquired environmentally, there will always be recurrences. The issue isn’t the rate of recurrence. It is whether the more invasive intervention reduces that rate. Then balance any measured reduction against the adverse effects of the invasive intervention, like PICC line infections. This Bayesian decision making is hard for some risk-adverse humans to assimilate.
Dr. Coon and associates have confirmed, using Big Data, that prolonged IV therapy of late-onset GBS bacteremia does not generate a clinically significant benefit. It is certainly possible to sow doubt by asking for proof in a variety of subpopulations. But this new article is in the context of multiple articles over the past decade that have disproved the myth of the superiority of IV therapy. Given the known risks and costs of PICC lines and prolonged IV therapy, the default should be, absent a credible rationale to the contrary, that oral therapy at home is better.
Dr. Coon and associates show that, by 2015, 5 of 49 children’s hospitals were early adopters and had made the switch to mostly using short treatment courses. Fourteen of 49 hadn’t changed at all. Given this new analysis, what are you laggards waiting for?
Dr. Kevin Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. He reported no relevant financial disclosures.
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
Infants with bacteremia caused by group B streptococcus (GBS) who were treated with intravenous antimicrobial therapy for 8 days or less had similarly successful outcomes, compared with those treated longer, based on data from 775 infants.
Current guidelines recommend intravenous antibiotics for a prolonged period of 10 days for infants (defined as 7-90 days old) with uncomplicated, late-onset GBS bacteremia, “however, no studies have compared outcomes among infants who receive prolonged versus shortened durations of IV antibiotic therapy,” wrote Eric R. Coon, MD, of the University of Utah, Salt Lake City, and colleagues. In a retrospective study published in Pediatrics, the researchers compared recurrence rates in infants who received prolonged vs. shortened therapy.
The study population included 612 infants with uncomplicated late-onset GBS bacteremia aged 4 months and younger who received prolonged IV therapy and 163 who received shortened therapy (defined as 8 days or less). Demographics were not significantly different between the groups, although infants who received a shortened treatment were more likely to be older, were more often admitted in later years of the study, and more likely to have a concomitant urinary tract infection.
Overall, 17 infants experienced recurrence; 3 in the shortened therapy group (1.8%) and 14 in the prolonged therapy group (2.3%). The average time to recurrence was 25 days.
Of note, 27 infants in the shortened treatment group received oral antibiotics on the day of their hospital discharge, and none of them experienced GBS recurrence, which suggests that “Early transition to oral antibiotic therapy may be appropriate for carefully selected infants with GBS bacteremia,” the researchers wrote.
In the prolonged treatment group, recurrence rates were 4.0% and 1.5%, respectively, for infants discharged with and without a peripherally inserted central catheter (PICC), but complications from the catheter may have been misclassified as disease recurrence to cause the difference in rate, as the noncatheter patients had similar recurrence rates to the shortened treatment group, the researchers noted.
“We found striking variation in IV antibiotic treatment duration by hospital and whether patients received prolonged or shortened IV courses; rates of GBS disease recurrence and treatment failure were low,” the researchers said. The top three antibiotics prescribed were ampicillin plus a third-generation cephalosporin (37%), third-generation cephalosporin monotherapy (28%), and third-generation cephalosporin monotherapy plus vancomycin (7%).
The findings were limited by the observational design, potential for misclassification of outcomes, and a lack of data to address the total duration of antibiotic therapy, the researchers noted. However, the results suggest that shorter treatment can be an informed decision considered in appropriate patients.
“Beyond decreased health care costs, shortened IV antibiotic courses provide the advantage of a diminished burden for families, allowing for patients to leave the hospital sooner, making it easier to administer the antibiotic at home, and decreasing the likelihood that they would develop a treatment-related complication,” the researchers said. The researchers had no financial conflicts to disclose.
SOURCE: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0131.
FROM PEDIATRICS
Key clinical point: Courses of IV antibiotics shorter than recommended for group B streptococcus bacteremia yield low rates of recurrence and treatment failure.
Major finding: Three children treated with a shorter IV duration had recurrence of group B strep, compared with 14 children in a longer treatment group (1.8% vs. 2.3%).
Study details: The data come from a multicenter retrospective cohort study of 775 infants aged 7 days to 4 months.
Disclosures: The researchers had no financial conflicts to disclose.
Source: Coon E et al. Pediatrics. 2018 Oct 11. doi: 10.1542/peds.2018-0345.
Treating cryptococcal meningitis in patients with HIV
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
One-week treatment with amphotericin B deoxycholate (AmBd)– and flucytosine (5FC)–based therapy, followed by fluconazole (FLU) on days 8 through 14, is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis, according to the authors of a review of the available literature in the Cochrane Database of Systemic Reviews.
The review is an update of one previous previously published in 2011. The authors found 13 eligible studies that enrolled 2,426 participants and compared 21 interventions. They performed a network meta-analysis using multivariate meta-regression, modeled treatment differences (RR and 95% confidence interval), and determined treatment rankings for 2-week and 10-week mortality outcomes using surface under the cumulative ranking curve, which represents the probability that a treatment will present the best outcome with no uncertainty and was used to develop a hierarchy of treatments for HIV-associated cryptococcal meningitis.
In addition, certainty of the evidence was assessed using the GRADE approach, according to Mark W. Tenforde, MD, of the University of Washington School of Public Health, Seattle, and his colleagues.
They found “reduced 10-week mortality with shortened [AmBd and 5FC] induction therapy, compared to the current gold standard of 2 weeks of AmBd and 5FC, based on moderate-certainty evidence.” They also found no mortality benefit of combination 2 weeks AmBd and FLU, compared with AmBd alone.
“In resource-limited settings, 1-week AmBd- and 5FC-based therapy is probably superior to other regimens for treatment of HIV-associated cryptococcal meningitis,” they wrote. “An all-oral regimen of 2 weeks 5FC and FLU may be an alternative in settings where AmBd is unavailable or intravenous therapy cannot be safely administered.” These results indicated the need to expand access to 5FC in resource-limited settings in which HIV-associated cryptococcal meningitis is most common.
They also reported finding no mortality benefit of 2 weeks of combination AmBd and FLU, compared with AmBd alone.
“Given the absence of data from studies in children, and limited data from high-income countries, our findings provide limited guidance for treatment in these patients and settings,” Dr. Tenforde and his colleagues stated.
The authors reported that they had no relevant conflicts of interest.
SOURCE: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.
FROM COCHRANE DATABASE OF SYSTEMIC REVIEWS
Key clinical point: Shorter drug treatment beat the gold standard for HIV-associated cryptococcal meningitis according to a literature review.
Major finding:
Study details: Updated review of articles, registries, and clinical trials during Jan. 1, 1980–July 9, 2018.
Disclosures: The authors reported that they had no relevant conflicts of interest.
Source: Tenforde MW et al. Treatment for HIV-associated cryptococcal meningitis. Cochrane Database Syst Rev. 2018 Jul 25;7:CD005647. doi: 10.1002/14651858.CD005647.