Infectious Diseases

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.

Jim Kling/MDedge News

The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.

“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.

She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.

It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.

“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.

Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.

The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.

“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.

She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
 

SOURCE: AASLD 2018, Abstract 0249.

Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.

Early-onset sepsis requires different management strategies in preterm and term neonates, according to a pair of clinical reports published in Pediatrics.

herjua/Thinkstock

Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.

In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.

Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.

“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.

In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.

Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.

There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.

They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.

The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.

The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.

The researchers had no financial conflicts to disclose, and there was no external funding.

SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.

Early-onset sepsis requires different management strategies in preterm and term neonates, according to a pair of clinical reports published in Pediatrics.

herjua/Thinkstock

Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.

In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.

Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.

“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.

In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.

Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.

There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.

They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.

The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.

The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.

The researchers had no financial conflicts to disclose, and there was no external funding.

SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.

Early-onset sepsis requires different management strategies in preterm and term neonates, according to a pair of clinical reports published in Pediatrics.

herjua/Thinkstock

Early-onset sepsis usually begins during labor in term infants, but in preterm infants, “the pathogenesis of preterm EOS likely begins before the onset of labor in many cases of preterm labor and/or PROM [premature rupture of membranes],” wrote Karen M. Puopolo, MD, of the University of Pennsylvania, Philadelphia, and her colleagues.

In the report on preterm infants, the researchers noted that EOS risk assessment using gestational age can be useful for term infants, but not for preterm infants. Instead, they advised categorizing preterm infants as low risk based on birth circumstances. Low-risk preterm infants were defined as those born by cesarean delivery because of maternal noninfectious illness or placental insufficiency in the absence of labor, attempts to induce labor, or rupture of membranes before delivery. Consider the risk/benefit balance of performing an EOS laboratory evaluation and empirical antibiotics, depending on the neonate’s clinical condition, the researchers said.

Preterm infants at high risk for EOS are those born preterm because of maternal cervical incompetence, preterm labor, premature rupture of membranes, clinical concerns for intra-amniotic infection, or acute onset of “unexplained nonreassuring fetal status,” Dr. Puopolo and her associates said. These infants should be managed with a blood culture and empirical antibiotics.

“The combination of ampicillin and gentamicin is the most appropriate empirical antibiotic regimen for infants at risk for EOS,” they noted. “Empirical administration of additional broad-spectrum antibiotics may be indicated in preterm infants who are severely ill and at a high risk for EOS, particularly after prolonged antepartum maternal antibiotic treatment,” they said. Antibiotics should be discontinued by 36-48 hours of incubation unless the infant shows signs of site-specific infection.

In the second report, again with Dr. Puopolo as the primary author, management of EOS was addressed for full-term infants, defined as those born at 35 weeks’ gestation or later.

Infants born at 35 weeks’ gestation or later can be stratified for EOS risk based on algorithms for intrapartum risk factors as well as risk assessments based on these risk factors and infant examinations, the researchers said.

There are a variety of acceptable approaches to risk stratification: categorical algorithms with threshold values for intrapartum risk factors; multivariate risk assessment based on both intrapartum risk factors (such as maternal chorioamnionitis, group B streptococcus colonization, adequacy of intrapartum antibiotic prophylaxis, and duration of ROM); and serial infant examination to detect clinical signs of illness after birth, Dr. Puopolo and her associates wrote.

They recommended that birth centers choose which type of EOS risk assessment to use and tailor it to their own situation. Once local guidelines are developed, ongoing surveillance is suggested.

The same recommendations apply to term infants as preterm infants regarding first-choice use of ampicillin and gentamicin when necessary, to be discontinued when blood cultures are sterile at 36-48 hours of incubation in the absence of site-specific infection, they said.

The reports do “not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate,” Dr. Puopolo and her associates noted.

The researchers had no financial conflicts to disclose, and there was no external funding.

SOURCE: Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2896; Puopolo KM et al. Pediatrics. 2018 Nov. doi: 10.1542/peds.2018-2894.

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

Risk stratification tools that omit lumbar puncture accurately classified most well-appearing febrile infants with invasive bacterial infections as being at low risk, results of a recent study show.

The modified Philadelphia criteria were highly sensitive for risk stratifying febrile infants, in a recent validation study based on a large, multicenter sample, investigators report. No infants with bacterial meningitis were classified as low risk using the modified criteria, which do not include routine testing of cerebrospinal fluid (CSF). Two infants with bacterial meningitis, both younger than 28 days old, were classified as low risk using the Rochester criteria, which also avoid routine lumbar puncture, investigators reported.

“Our findings support the use of the modified Philadelphia criteria without routine CSF testing for febrile infants in the second month of life,” the investigators said in their report, published in Pediatrics.

However, to confirm the safety of omitting CSF testing in low-risk febrile infants older than 28 days, a prospective study will be needed, cautioned the researchers, led by Paul L. Aronson, MD, of the department of pediatrics at Yale University in New Haven, Conn.

Nevertheless, some clinicians do not automatically perform CSF testing in infants older than 28 days because of the rarity of bacterial meningitis in that age group, they said in the report.

The study by Dr. Aronson and colleagues was based on data for infants younger than 60 days of age seen in the emergency departments of 9 hospitals between July 2011 and June 2016. The final sample included 135 infants with invasive bacterial infections, including 118 who had bacteremia without meningitis and 17 who had bacterial meningitis, along with 249 matched febrile infant controls.

A total of 25 infants with invasive bacterial infections were classified as low risk by the Rochester criteria, and 11 of those were low risk by the modified Philadelphia criteria, investigators said.

Compared with the modified Philadelphia criteria, the Rochester criteria had a lower sensitivity (81.5% vs. 91.9%; P = 0.01) and a higher specificity (59.8 vs. 34.5%; P less than 0.001).

Out of the 11 infants deemed low risk per the modified Philadelphia criteria, none were diagnosed with bacterial meningitis. By contrast, 2 of the 25 infants who were low risk per the Rochester criteria had bacterial meningitis, and both were younger than or equal to 28 days of age. “Both of these infants would have been classified as high risk per the modified Philadelphia criteria,” Dr. Aronson and his coauthors said.

Based on the findings of this study, caution should be exercised in applying low-risk criteria to infants 28 days of age or younger, according to the investigators.

“Febrile infants discharged from the emergency department without CSF testing should have close outpatient follow-up,” they wrote.

Dr. Aronson and his coauthors reported that they had no relevant disclosures. One coauthor reported serving as an expert witness in malpractice cases involving evaluation of febrile children.

SOURCE: Aronson PL et al. Pediatrics. 13 Nov 2018. doi: 10.1542/peds.2018-1879).

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Among patients with adult congenital heart disease (ACHD), hepatitis C virus antibody positivity was significantly associated with a composite end point that comprised cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation, according to a report published online in the American Journal of Cardiology.

American Heart Association

The study retrospectively enrolled 243 ACHD patients (mean age 26 years) who underwent cardiac surgery before 1992 and visited a single hospital during 1995-2015. Clinical characteristics, including cardiac function and long-term prognosis, were compared between HCV antibody–positive (48) and –negative (195) patients, according to Ryo Konno, MD, of Tohoku University, Sendai, Japan, and his colleagues.

They found that the prevalence of reduced systemic ventricular ejection fraction less than 50% was significantly higher in the HCV antibody–positive group than in the HCV antibody–negative group (17 vs. 5.4%; P = .014), and that during a mean follow-up of 10 years the composite end point occurred in 51 patients.

Overall, Kaplan-Meier analysis showed the HCV antibody–positive group had significantly poorer event-free survival than the HCV antibody–negative group (P = .002). In addition, HCV antibody positivity was significantly associated with the composite end point in both univariable and multivariable Cox regression models (hazard ratio, 2.37; P = .005 and HR, 1.96; P = .032, respectively).

“These results indicate that screening for HCV should be performed in all ACHD patients with a history of heart surgery before 1992. Further, cardiac functions should be monitored more frequently to detect [stroke volume] dysfunction earlier in case of a positive result. These management strategies may have a beneficial impact on the long-term prognosis in this population,” Dr. Konno and his colleagues concluded.

The research was supported by the Japan Agency for Medical Research and the authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Konno R. et al. Am J Card. 2018;122:1965-71.

Clinical question: Does testing procalcitonin for lower respiratory tract infections (LRTIs) decrease total antibiotic days without a resultant increase in adverse events?

Background: LRTIs are frequently overtreated with antibiotics. Procalcitonin may indicate bacterial infection and promote antibacterial stewardship. Studies to evaluate how testing procalcitonin affects antibiotic use for suspected lower respiratory tract infections are limited.

Study design: Randomized 1:1 intention-to-treat, multicenter trial.

Setting: 14 U.S. urban academic hospitals.

Image

Dr. Naderi is assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Does testing procalcitonin for lower respiratory tract infections (LRTIs) decrease total antibiotic days without a resultant increase in adverse events?

Background: LRTIs are frequently overtreated with antibiotics. Procalcitonin may indicate bacterial infection and promote antibacterial stewardship. Studies to evaluate how testing procalcitonin affects antibiotic use for suspected lower respiratory tract infections are limited.

Study design: Randomized 1:1 intention-to-treat, multicenter trial.

Setting: 14 U.S. urban academic hospitals.

Image

Dr. Naderi is assistant professor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Does testing procalcitonin for lower respiratory tract infections (LRTIs) decrease total antibiotic days without a resultant increase in adverse events?

Background: LRTIs are frequently overtreated with antibiotics. Procalcitonin may indicate bacterial infection and promote antibacterial stewardship. Studies to evaluate how testing procalcitonin affects antibiotic use for suspected lower respiratory tract infections are limited.

Study design: Randomized 1:1 intention-to-treat, multicenter trial.

Setting: 14 U.S. urban academic hospitals.

Image

Dr. Naderi is assistant professor in the division of hospital medicine, University of Colorado, Denver.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

SAN FRANCISCO – People who inject drugs, including those with ongoing injection drug use and challenging demographic characteristics, have high rates of hepatitis C virus treatment completion and cure, preliminary results from an ongoing study showed.

“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”

In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.

The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).

Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.

Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.

When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”

Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”

Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.

[email protected]

Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.

ORLANDO – More therapies are becoming available for children for the treatment of influenza and multidrug-resistant infections such as Enterobacteriaceae and Acinetobacter, John S. Bradley, MD, said at the annual meeting of the American Academy of Pediatrics.

Dr. Bradley, director of the division of infectious diseases at Rady Children’s Hospital–San Diego, discussed a therapy for influenza, baloxavir, which was recently approved as a fast-acting single-dose medication and currently is under study in children. Also, a recent double-blind, phase 3 trial in the New England Journal of Medicine recruited patients as young as 12 years old. In the study, patients in the intervention group resolved their fever in median 25 hours, compared with 42 hours in the placebo group. Baloxavir better reduced viral load at day 2, compared with oseltamivir and placebo, but there was a similar alleviation of symptoms between both groups. There was a greater incidence of nausea and vomiting among the oseltamivir group, while the baloxavir group had a higher rate of diarrhea (N Engl J Med 2018;379:913-23).

However, Dr. Bradley noted baloxavir is much more expensive than oseltamivir, which may not justify the better tolerance of the drug for influenza treatment.

You don’t get better with it faster, so I’m not going to be recommending you all run to baloxavir this flu season for kids 12 years of age and older,” Dr. Bradley said. “I think oseltamivir is still fine, unless we end up with oseltamivir resistance.”

Solithromycin, an intravenous and oral fluoroketolide, has shown promising results against gram-positive and gram-negative pathogens for community-acquired pneumonia and other infections. During the drug’s study period, Cempra sold solithromycin to Melinta. However, one trial showed elevated liver functions in a higher number of patients than expected, and the Food and Drug Administration asked Melinta to conduct additional studies. Investigations on solithromycin have currently stopped until Melinta secures funding. “Until they get better resources, this particular drug is on hold, but you’ll see it again, I’m sure,” said Dr. Bradley, who also is professor and chief of the division of infectious diseases at the University of California, San Diego.

Dr. Bradley also discussed the efficacy of tedizolid, a protein synthesis inhibitor similar to linezolid approved in adults for the treatment of skin infections. He noted tedizolid is more active than linezolid, but the treatment course is a shorter dose for a shorter amount of time. Compared with linezolid, which can cause thrombocytopenia or neutropenia if taken for more than 10 days to 14 days, there also are fewer side effects.

“The tedizolid is much, much safer,” Dr. Bradley said, who added that trials for efficacy of tedizolid are currently underway in pediatric patients. “We’re hoping that will end up being the pediatric oxazolidinone.”

Other investigative therapies approved for adults and under study for use in children include ceftazidime/avibactam for treatment of urinary tract and complicated intra-abdominal infections, which is effective against meropenem-resistant Enterobacteriaceae and resistant Escherichia coli with extended-spectrum beta-lactamases (ESBL); ceftolozane/tazobactam has also been approved for adults, is pending approval in pediatric patients, and is active against ESBLs such as Pseudomonas; and meropenem/vaborbactam, which is active against Klebsiella pneumoniae carbapenemase (KPC)–producing isolates. Plazomicin, an aminoglycoside similar to gentamicin used to treat KPC-producing isolates, is stable against enzymes that degrade gentamicin and tobramycin.

CDC/ Matthew J. Arduino

Therapies currently under study for adults and being considered for children include imipenem/relebactam for treatment against E. coli, Enterobacter species, and KPC-producing isolates, and cefiderocol, a siderophore cephalosporin antibiotic – commonly described as a “Trojan horse” antibiotic because it binds to iron and is actively transported into the organism – is effective against Pseudomonas and has finished phase 2 trials in adults, with researchers looking to do single-dose trials in children, Dr. Bradley noted.

More experimentally, phage therapy for multidrug-resistant Acinetobacter baumannii proved effective in a 68-year-old patient with necrotizing pancreatitis who continued to deteriorate over a 4-month period despite multiple courses of antibiotics and attempted drainage of a pancreatic pseudocyst. Researchers selected a phage-specific bacterium with specificity for A. baumannii and cured him. “This is like science fiction,” Dr. Bradley said.

Dr. Bradley reported no relevant conflicts of interest.

ORLANDO – More therapies are becoming available for children for the treatment of influenza and multidrug-resistant infections such as Enterobacteriaceae and Acinetobacter, John S. Bradley, MD, said at the annual meeting of the American Academy of Pediatrics.

Dr. Bradley, director of the division of infectious diseases at Rady Children’s Hospital–San Diego, discussed a therapy for influenza, baloxavir, which was recently approved as a fast-acting single-dose medication and currently is under study in children. Also, a recent double-blind, phase 3 trial in the New England Journal of Medicine recruited patients as young as 12 years old. In the study, patients in the intervention group resolved their fever in median 25 hours, compared with 42 hours in the placebo group. Baloxavir better reduced viral load at day 2, compared with oseltamivir and placebo, but there was a similar alleviation of symptoms between both groups. There was a greater incidence of nausea and vomiting among the oseltamivir group, while the baloxavir group had a higher rate of diarrhea (N Engl J Med 2018;379:913-23).

However, Dr. Bradley noted baloxavir is much more expensive than oseltamivir, which may not justify the better tolerance of the drug for influenza treatment.

You don’t get better with it faster, so I’m not going to be recommending you all run to baloxavir this flu season for kids 12 years of age and older,” Dr. Bradley said. “I think oseltamivir is still fine, unless we end up with oseltamivir resistance.”

Solithromycin, an intravenous and oral fluoroketolide, has shown promising results against gram-positive and gram-negative pathogens for community-acquired pneumonia and other infections. During the drug’s study period, Cempra sold solithromycin to Melinta. However, one trial showed elevated liver functions in a higher number of patients than expected, and the Food and Drug Administration asked Melinta to conduct additional studies. Investigations on solithromycin have currently stopped until Melinta secures funding. “Until they get better resources, this particular drug is on hold, but you’ll see it again, I’m sure,” said Dr. Bradley, who also is professor and chief of the division of infectious diseases at the University of California, San Diego.

Dr. Bradley also discussed the efficacy of tedizolid, a protein synthesis inhibitor similar to linezolid approved in adults for the treatment of skin infections. He noted tedizolid is more active than linezolid, but the treatment course is a shorter dose for a shorter amount of time. Compared with linezolid, which can cause thrombocytopenia or neutropenia if taken for more than 10 days to 14 days, there also are fewer side effects.

“The tedizolid is much, much safer,” Dr. Bradley said, who added that trials for efficacy of tedizolid are currently underway in pediatric patients. “We’re hoping that will end up being the pediatric oxazolidinone.”

Other investigative therapies approved for adults and under study for use in children include ceftazidime/avibactam for treatment of urinary tract and complicated intra-abdominal infections, which is effective against meropenem-resistant Enterobacteriaceae and resistant Escherichia coli with extended-spectrum beta-lactamases (ESBL); ceftolozane/tazobactam has also been approved for adults, is pending approval in pediatric patients, and is active against ESBLs such as Pseudomonas; and meropenem/vaborbactam, which is active against Klebsiella pneumoniae carbapenemase (KPC)–producing isolates. Plazomicin, an aminoglycoside similar to gentamicin used to treat KPC-producing isolates, is stable against enzymes that degrade gentamicin and tobramycin.

CDC/ Matthew J. Arduino

Therapies currently under study for adults and being considered for children include imipenem/relebactam for treatment against E. coli, Enterobacter species, and KPC-producing isolates, and cefiderocol, a siderophore cephalosporin antibiotic – commonly described as a “Trojan horse” antibiotic because it binds to iron and is actively transported into the organism – is effective against Pseudomonas and has finished phase 2 trials in adults, with researchers looking to do single-dose trials in children, Dr. Bradley noted.

More experimentally, phage therapy for multidrug-resistant Acinetobacter baumannii proved effective in a 68-year-old patient with necrotizing pancreatitis who continued to deteriorate over a 4-month period despite multiple courses of antibiotics and attempted drainage of a pancreatic pseudocyst. Researchers selected a phage-specific bacterium with specificity for A. baumannii and cured him. “This is like science fiction,” Dr. Bradley said.

Dr. Bradley reported no relevant conflicts of interest.

ORLANDO – More therapies are becoming available for children for the treatment of influenza and multidrug-resistant infections such as Enterobacteriaceae and Acinetobacter, John S. Bradley, MD, said at the annual meeting of the American Academy of Pediatrics.

Dr. Bradley, director of the division of infectious diseases at Rady Children’s Hospital–San Diego, discussed a therapy for influenza, baloxavir, which was recently approved as a fast-acting single-dose medication and currently is under study in children. Also, a recent double-blind, phase 3 trial in the New England Journal of Medicine recruited patients as young as 12 years old. In the study, patients in the intervention group resolved their fever in median 25 hours, compared with 42 hours in the placebo group. Baloxavir better reduced viral load at day 2, compared with oseltamivir and placebo, but there was a similar alleviation of symptoms between both groups. There was a greater incidence of nausea and vomiting among the oseltamivir group, while the baloxavir group had a higher rate of diarrhea (N Engl J Med 2018;379:913-23).

However, Dr. Bradley noted baloxavir is much more expensive than oseltamivir, which may not justify the better tolerance of the drug for influenza treatment.

You don’t get better with it faster, so I’m not going to be recommending you all run to baloxavir this flu season for kids 12 years of age and older,” Dr. Bradley said. “I think oseltamivir is still fine, unless we end up with oseltamivir resistance.”

Solithromycin, an intravenous and oral fluoroketolide, has shown promising results against gram-positive and gram-negative pathogens for community-acquired pneumonia and other infections. During the drug’s study period, Cempra sold solithromycin to Melinta. However, one trial showed elevated liver functions in a higher number of patients than expected, and the Food and Drug Administration asked Melinta to conduct additional studies. Investigations on solithromycin have currently stopped until Melinta secures funding. “Until they get better resources, this particular drug is on hold, but you’ll see it again, I’m sure,” said Dr. Bradley, who also is professor and chief of the division of infectious diseases at the University of California, San Diego.

Dr. Bradley also discussed the efficacy of tedizolid, a protein synthesis inhibitor similar to linezolid approved in adults for the treatment of skin infections. He noted tedizolid is more active than linezolid, but the treatment course is a shorter dose for a shorter amount of time. Compared with linezolid, which can cause thrombocytopenia or neutropenia if taken for more than 10 days to 14 days, there also are fewer side effects.

“The tedizolid is much, much safer,” Dr. Bradley said, who added that trials for efficacy of tedizolid are currently underway in pediatric patients. “We’re hoping that will end up being the pediatric oxazolidinone.”

Other investigative therapies approved for adults and under study for use in children include ceftazidime/avibactam for treatment of urinary tract and complicated intra-abdominal infections, which is effective against meropenem-resistant Enterobacteriaceae and resistant Escherichia coli with extended-spectrum beta-lactamases (ESBL); ceftolozane/tazobactam has also been approved for adults, is pending approval in pediatric patients, and is active against ESBLs such as Pseudomonas; and meropenem/vaborbactam, which is active against Klebsiella pneumoniae carbapenemase (KPC)–producing isolates. Plazomicin, an aminoglycoside similar to gentamicin used to treat KPC-producing isolates, is stable against enzymes that degrade gentamicin and tobramycin.

CDC/ Matthew J. Arduino

Therapies currently under study for adults and being considered for children include imipenem/relebactam for treatment against E. coli, Enterobacter species, and KPC-producing isolates, and cefiderocol, a siderophore cephalosporin antibiotic – commonly described as a “Trojan horse” antibiotic because it binds to iron and is actively transported into the organism – is effective against Pseudomonas and has finished phase 2 trials in adults, with researchers looking to do single-dose trials in children, Dr. Bradley noted.

More experimentally, phage therapy for multidrug-resistant Acinetobacter baumannii proved effective in a 68-year-old patient with necrotizing pancreatitis who continued to deteriorate over a 4-month period despite multiple courses of antibiotics and attempted drainage of a pancreatic pseudocyst. Researchers selected a phage-specific bacterium with specificity for A. baumannii and cured him. “This is like science fiction,” Dr. Bradley said.

Dr. Bradley reported no relevant conflicts of interest.