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FDA OKs first fecal transplant therapy for recurrent C. difficile
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Rebyota (fecal microbiota, live-jslm), from Ferring Pharmaceuticals, is intended for use after an individual has completed antibiotic treatment for recurrent CDI. It is not indicated for the first occurrence of CDI.
“Recurrent CDI impacts an individual’s quality of life and can also potentially be life-threatening,” Peter Marks, MD, PhD, director, FDA Center for Biologics Evaluation and Research, said in a statement announcing approval.
As the first FDA-approved fecal microbiota product, this approval “represents an important milestone, as it provides an additional approved option to prevent recurrent CDI,” Dr. Marks added.
A panel of FDA advisors recommended approval of Rebyota in September.
The application for Rebyota received priority review and had orphan drug and breakthrough therapy designation.
A vicious cycle
Treatment options for recurrent CDI are limited. It’s been estimated that up to one-third of CDI cases recur, and people who suffer a recurrent bout of CDI are at a significantly higher risk for further infections.
Following the first recurrence, up to two-thirds of patients may experience a subsequent recurrence. Antibiotics used to treat CDI may contribute to a cycle of recurrence by altering the gut flora. The administration of fecal microbiota helps restore the gut flora to prevent further episodes of CDI.
Rebyota is a microbiota-based live biotherapeutic prepared from human stool collected from prescreened, qualified donors. It comes prepackaged in a single dose that is administered rectally.
The safety and efficacy of Rebyota were assessed in five clinical trials with more than 1,000 participants, the company notes in a press release.
In one trial, following a standard course of antibiotics, a one-time treatment with Rebyota was successful for three-quarters of participants at 8 weeks.
The treatment also prevented additional bouts; 84% of these initial responders remaining free of CDI at 6 months.
Two-thirds of participants reported treatment-emergent adverse events. Most events were mild to moderate in severity. Diarrhea and abdominal pain were the most common.
The data, from the ongoing PUNCH CD3-OLS study, were presented in October at the annual meeting of the American College of Gastroenterology and were published simultaneously in the journal Drugs.
“This is a positive adjunct to our current therapies for C. difficile in terms of trying to knock it out once a standard course of antibiotics has been administered,” Lisa Malter, MD, a gastroenterologist and professor of medicine at New York University Langone Health, said in an interview.
Dr. Malter acknowledged that because it’s delivered rectally, there could be “some hesitation” on the patient’s part to undergo the therapy.
However, C. difficile can be “excruciating” for patients, and they “may be more than willing to take [this agent] because it gets them feeling better,” Dr. Malter said.
Full prescribing information for Rebyota is available online.
Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Don’t let amoxicillin shortage go to waste, antibiotic stewards say
Some experts are encouraging clinicians to see the amoxicillin shortage through pink-colored glasses.
The ongoing shortage, which was first reported in October and was prompted by a surge in demand linked in part to influenza and respiratory syncytial virus (RSV), could be an opportunity for clinicians to refine their prescribing practices and avoid unnecessary and potentially harmful orders for the medication, they say.
Antibiotics are often prescribed to patients who do not need them. In many cases, patients’ symptoms are caused by viral infections, not bacteria, so antibiotics do not help.
Even when symptoms resolve after a patient takes an antibiotic, the drug may have had nothing to do with their improvement.
Time to double-down on assessment; use antibiotics only when needed,” Jason Gallagher, PharmD, of Temple University School of Pharmacy in Philadelphia, posted on Twitter.
When antibiotics are not helping, they still may cause harm. Treatment with antibiotics entails risks for antibiotic resistance, infection with Clostridioides difficile, and side effects, such as rashes and – as Dr. Gallagher noted – diarrhea.
“They say ‘never let a good shortage go to waste,’ ” Michael Cosimini, MD, a pediatrician at Oregon Health & Science University, Portland, tweeted about the lack of amoxicillin in October.
Dr. Cosimini offered his thoughts about “improving our amoxicillin prescribing patterns” in pediatrics and encouraged colleagues to do so.
For example, he highlighted guidelines that state that antimicrobial therapy is not routinely required for preschool-aged children with community-acquired pneumonia (CAP) because most cases are caused by viral pathogens.
And trials show that when antibiotics are used for CAP, a shorter treatment duration, such as 5 days, rather than the standard 7-10 days, can be sufficient.
“As physicians, a shortage like this is an opportunity to do our best in the short term, as well as reflect on our current practice and make changes for the better in the long run,” Dr. Cosimini told this news organization.
Amoxicillin is the most commonly prescribed antibiotic in the outpatient setting and is the first choice among antimicrobial agents for common infections, such as otitis media, strep throat, and pneumonia, he said. “We use it frequently, so even small changes could go a long way to improve our prescribing practice,” Dr. Cosimini said.
Inappropriate antibiotic prescribing may be common
A 2021 statement on antibiotic stewardship from the American Academy of Pediatrics (AAP) declared that while antibiotics have saved countless lives, they can also cause harm and are frequently used inappropriately.
“One in five pediatric ambulatory visits result in an antibiotic prescription, accounting for nearly 50 million antibiotic prescriptions annually in the United States, at least half of which are considered inappropriate. [Acute respiratory tract infections] account for more than two-thirds of antibiotic prescriptions for children, at least one-third of which are unnecessary,” according to the society.
Outpatient antibiotic stewardship efforts could focus on clinical encounters in which the medications could be avoided altogether, the AAP suggested.
“Examples include antibiotic prescribing for nonspecific upper respiratory infection, bronchiolitis, acute bronchitis, asthma exacerbation, or conjunctivitis,” the group said.
Given the epidemiology of bacterial infections seen in ambulatory care settings that warrant antibiotic therapy, researchers conservatively estimate “that antibiotic prescribing could be safely reduced by 30%,” the statement noted.
That said, treatment decisions are not always clear cut.
“Certain infections in children, such as ear infections and lung infections, can be caused by viruses, bacteria, or both at the same time,” Dr. Cosimini said. “As such, it is very difficult to know which children benefit from which antibiotics.”
Watching, waiting, vaccinating
Pediatricians know that many children with ear infections will get better without antibiotics. “Parents should know that their doctor may suggest watching an ear infection without antibiotics, as is the recommendation from the AAP,” Dr. Cosimini said.
Data indicate that doctors are not following this practice as often as they could be, he said.
When antibiotic treatment is needed during the shortage, agents other than amoxicillin suspension can be used.
“Even though amoxicillin suspension is our go-to antibiotic for many infections, there are effective alternative options,” Dr. Cosimini said. “Children’s Hospital of Philadelphia has a good list for doctors looking for alternatives.”
Another approach to reducing the use of antibiotics in the future involves preventing infections through vaccination.
Research shows that routine childhood vaccines may have averted millions of respiratory and ear infections. And because bacterial infections can follow viral infections, the annual flu vaccine and COVID-19 vaccines “are also great tools to reduce antibiotic use,” Dr. Cosimini said.
A turn to more toxic options?
The shortage of amoxicillin oral powder for suspension was reported by the Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) in October.
On Nov. 4, the Society of Infectious Diseases Pharmacists (SIDP) issued a statement on the amoxicillin shortage, noting that increased demand for the drug coincided with a surge in respiratory viral infections, including RSV and influenza, among children.
“Though supportive care is the mainstay of treatment for viral infections, antibiotics may be indicated for the treatment of superimposed bacterial infections, including pneumonia and acute otitis media,” the SIDP statement said. “While alternative antibiotics may be available depending on the indication, many have a broader spectrum of activity, increased toxicity, and excess cost relative to amoxicillin. Furthermore, it is anticipated alternatives may soon become in short supply as well, given increased usage.”
SIDP “encourages the judicious use of antibiotics” and supports watch-and-wait strategies and the use of the shortest effective duration of therapy when appropriate.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, monitors around 250 drug shortages at any given time.
The amoxicillin shortage, while not “overly worrisome,” stands out because of how widely the drug is used and the fact that the shortage appears to have been sparked by an increase in demand rather than supply chain or manufacturing quality problems that more typically lead to shortages, he said.
Unlike some other shortages, the amoxicillin shortfall largely does not involve disrupting a medication regimen that someone was already receiving, and substitutions should be available.
“That said, it’s very, very disruptive to parents or a caregiver when you have a sick child who needs an antibiotic and it’s not available,” Dr. Ganio said.
Can a poster change practice?
In an unrelated move, the U.S. Agency for Healthcare Research and Quality published new resources and strategies to reduce inappropriate antibiotic use in ambulatory care settings.
One of the tools is a poster that doctors can print and hang in their offices. It states: “We commit to only prescribing antibiotics when they will help you. Taking antibiotics when you do not need them will NOT make you better. You will still feel sick, and the antibiotic may give you a skin rash, diarrhea, or a yeast infection.”
Jeffrey A. Linder, MD, MPH, a general internist and researcher at Northwestern University in Chicago, helped develop some of the approaches to improve prescribing practices in primary care.
Dr. Linder explained on a recent episode of the Freakonomics, M.D. podcast that the poster can be key.
One reason clinicians may prescribe antibiotics inappropriately is because they assume – perhaps erroneously – that patients want and expect them. By addressing the issue up front by displaying the poster, they may be able to “short-circuit” that type of thinking.
A minority of patients do expect antibiotics. “But the vast majority of patients are thinking, ‘I don’t feel well, I want to know what’s going on, and I want to know how to feel better and what’s going to happen.’ ”
For their part, patients can tell their doctors that they want an antibiotic only if they really need it, Dr. Linder said.
A version of this article first appeared on Medscape.com.
Some experts are encouraging clinicians to see the amoxicillin shortage through pink-colored glasses.
The ongoing shortage, which was first reported in October and was prompted by a surge in demand linked in part to influenza and respiratory syncytial virus (RSV), could be an opportunity for clinicians to refine their prescribing practices and avoid unnecessary and potentially harmful orders for the medication, they say.
Antibiotics are often prescribed to patients who do not need them. In many cases, patients’ symptoms are caused by viral infections, not bacteria, so antibiotics do not help.
Even when symptoms resolve after a patient takes an antibiotic, the drug may have had nothing to do with their improvement.
Time to double-down on assessment; use antibiotics only when needed,” Jason Gallagher, PharmD, of Temple University School of Pharmacy in Philadelphia, posted on Twitter.
When antibiotics are not helping, they still may cause harm. Treatment with antibiotics entails risks for antibiotic resistance, infection with Clostridioides difficile, and side effects, such as rashes and – as Dr. Gallagher noted – diarrhea.
“They say ‘never let a good shortage go to waste,’ ” Michael Cosimini, MD, a pediatrician at Oregon Health & Science University, Portland, tweeted about the lack of amoxicillin in October.
Dr. Cosimini offered his thoughts about “improving our amoxicillin prescribing patterns” in pediatrics and encouraged colleagues to do so.
For example, he highlighted guidelines that state that antimicrobial therapy is not routinely required for preschool-aged children with community-acquired pneumonia (CAP) because most cases are caused by viral pathogens.
And trials show that when antibiotics are used for CAP, a shorter treatment duration, such as 5 days, rather than the standard 7-10 days, can be sufficient.
“As physicians, a shortage like this is an opportunity to do our best in the short term, as well as reflect on our current practice and make changes for the better in the long run,” Dr. Cosimini told this news organization.
Amoxicillin is the most commonly prescribed antibiotic in the outpatient setting and is the first choice among antimicrobial agents for common infections, such as otitis media, strep throat, and pneumonia, he said. “We use it frequently, so even small changes could go a long way to improve our prescribing practice,” Dr. Cosimini said.
Inappropriate antibiotic prescribing may be common
A 2021 statement on antibiotic stewardship from the American Academy of Pediatrics (AAP) declared that while antibiotics have saved countless lives, they can also cause harm and are frequently used inappropriately.
“One in five pediatric ambulatory visits result in an antibiotic prescription, accounting for nearly 50 million antibiotic prescriptions annually in the United States, at least half of which are considered inappropriate. [Acute respiratory tract infections] account for more than two-thirds of antibiotic prescriptions for children, at least one-third of which are unnecessary,” according to the society.
Outpatient antibiotic stewardship efforts could focus on clinical encounters in which the medications could be avoided altogether, the AAP suggested.
“Examples include antibiotic prescribing for nonspecific upper respiratory infection, bronchiolitis, acute bronchitis, asthma exacerbation, or conjunctivitis,” the group said.
Given the epidemiology of bacterial infections seen in ambulatory care settings that warrant antibiotic therapy, researchers conservatively estimate “that antibiotic prescribing could be safely reduced by 30%,” the statement noted.
That said, treatment decisions are not always clear cut.
“Certain infections in children, such as ear infections and lung infections, can be caused by viruses, bacteria, or both at the same time,” Dr. Cosimini said. “As such, it is very difficult to know which children benefit from which antibiotics.”
Watching, waiting, vaccinating
Pediatricians know that many children with ear infections will get better without antibiotics. “Parents should know that their doctor may suggest watching an ear infection without antibiotics, as is the recommendation from the AAP,” Dr. Cosimini said.
Data indicate that doctors are not following this practice as often as they could be, he said.
When antibiotic treatment is needed during the shortage, agents other than amoxicillin suspension can be used.
“Even though amoxicillin suspension is our go-to antibiotic for many infections, there are effective alternative options,” Dr. Cosimini said. “Children’s Hospital of Philadelphia has a good list for doctors looking for alternatives.”
Another approach to reducing the use of antibiotics in the future involves preventing infections through vaccination.
Research shows that routine childhood vaccines may have averted millions of respiratory and ear infections. And because bacterial infections can follow viral infections, the annual flu vaccine and COVID-19 vaccines “are also great tools to reduce antibiotic use,” Dr. Cosimini said.
A turn to more toxic options?
The shortage of amoxicillin oral powder for suspension was reported by the Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) in October.
On Nov. 4, the Society of Infectious Diseases Pharmacists (SIDP) issued a statement on the amoxicillin shortage, noting that increased demand for the drug coincided with a surge in respiratory viral infections, including RSV and influenza, among children.
“Though supportive care is the mainstay of treatment for viral infections, antibiotics may be indicated for the treatment of superimposed bacterial infections, including pneumonia and acute otitis media,” the SIDP statement said. “While alternative antibiotics may be available depending on the indication, many have a broader spectrum of activity, increased toxicity, and excess cost relative to amoxicillin. Furthermore, it is anticipated alternatives may soon become in short supply as well, given increased usage.”
SIDP “encourages the judicious use of antibiotics” and supports watch-and-wait strategies and the use of the shortest effective duration of therapy when appropriate.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, monitors around 250 drug shortages at any given time.
The amoxicillin shortage, while not “overly worrisome,” stands out because of how widely the drug is used and the fact that the shortage appears to have been sparked by an increase in demand rather than supply chain or manufacturing quality problems that more typically lead to shortages, he said.
Unlike some other shortages, the amoxicillin shortfall largely does not involve disrupting a medication regimen that someone was already receiving, and substitutions should be available.
“That said, it’s very, very disruptive to parents or a caregiver when you have a sick child who needs an antibiotic and it’s not available,” Dr. Ganio said.
Can a poster change practice?
In an unrelated move, the U.S. Agency for Healthcare Research and Quality published new resources and strategies to reduce inappropriate antibiotic use in ambulatory care settings.
One of the tools is a poster that doctors can print and hang in their offices. It states: “We commit to only prescribing antibiotics when they will help you. Taking antibiotics when you do not need them will NOT make you better. You will still feel sick, and the antibiotic may give you a skin rash, diarrhea, or a yeast infection.”
Jeffrey A. Linder, MD, MPH, a general internist and researcher at Northwestern University in Chicago, helped develop some of the approaches to improve prescribing practices in primary care.
Dr. Linder explained on a recent episode of the Freakonomics, M.D. podcast that the poster can be key.
One reason clinicians may prescribe antibiotics inappropriately is because they assume – perhaps erroneously – that patients want and expect them. By addressing the issue up front by displaying the poster, they may be able to “short-circuit” that type of thinking.
A minority of patients do expect antibiotics. “But the vast majority of patients are thinking, ‘I don’t feel well, I want to know what’s going on, and I want to know how to feel better and what’s going to happen.’ ”
For their part, patients can tell their doctors that they want an antibiotic only if they really need it, Dr. Linder said.
A version of this article first appeared on Medscape.com.
Some experts are encouraging clinicians to see the amoxicillin shortage through pink-colored glasses.
The ongoing shortage, which was first reported in October and was prompted by a surge in demand linked in part to influenza and respiratory syncytial virus (RSV), could be an opportunity for clinicians to refine their prescribing practices and avoid unnecessary and potentially harmful orders for the medication, they say.
Antibiotics are often prescribed to patients who do not need them. In many cases, patients’ symptoms are caused by viral infections, not bacteria, so antibiotics do not help.
Even when symptoms resolve after a patient takes an antibiotic, the drug may have had nothing to do with their improvement.
Time to double-down on assessment; use antibiotics only when needed,” Jason Gallagher, PharmD, of Temple University School of Pharmacy in Philadelphia, posted on Twitter.
When antibiotics are not helping, they still may cause harm. Treatment with antibiotics entails risks for antibiotic resistance, infection with Clostridioides difficile, and side effects, such as rashes and – as Dr. Gallagher noted – diarrhea.
“They say ‘never let a good shortage go to waste,’ ” Michael Cosimini, MD, a pediatrician at Oregon Health & Science University, Portland, tweeted about the lack of amoxicillin in October.
Dr. Cosimini offered his thoughts about “improving our amoxicillin prescribing patterns” in pediatrics and encouraged colleagues to do so.
For example, he highlighted guidelines that state that antimicrobial therapy is not routinely required for preschool-aged children with community-acquired pneumonia (CAP) because most cases are caused by viral pathogens.
And trials show that when antibiotics are used for CAP, a shorter treatment duration, such as 5 days, rather than the standard 7-10 days, can be sufficient.
“As physicians, a shortage like this is an opportunity to do our best in the short term, as well as reflect on our current practice and make changes for the better in the long run,” Dr. Cosimini told this news organization.
Amoxicillin is the most commonly prescribed antibiotic in the outpatient setting and is the first choice among antimicrobial agents for common infections, such as otitis media, strep throat, and pneumonia, he said. “We use it frequently, so even small changes could go a long way to improve our prescribing practice,” Dr. Cosimini said.
Inappropriate antibiotic prescribing may be common
A 2021 statement on antibiotic stewardship from the American Academy of Pediatrics (AAP) declared that while antibiotics have saved countless lives, they can also cause harm and are frequently used inappropriately.
“One in five pediatric ambulatory visits result in an antibiotic prescription, accounting for nearly 50 million antibiotic prescriptions annually in the United States, at least half of which are considered inappropriate. [Acute respiratory tract infections] account for more than two-thirds of antibiotic prescriptions for children, at least one-third of which are unnecessary,” according to the society.
Outpatient antibiotic stewardship efforts could focus on clinical encounters in which the medications could be avoided altogether, the AAP suggested.
“Examples include antibiotic prescribing for nonspecific upper respiratory infection, bronchiolitis, acute bronchitis, asthma exacerbation, or conjunctivitis,” the group said.
Given the epidemiology of bacterial infections seen in ambulatory care settings that warrant antibiotic therapy, researchers conservatively estimate “that antibiotic prescribing could be safely reduced by 30%,” the statement noted.
That said, treatment decisions are not always clear cut.
“Certain infections in children, such as ear infections and lung infections, can be caused by viruses, bacteria, or both at the same time,” Dr. Cosimini said. “As such, it is very difficult to know which children benefit from which antibiotics.”
Watching, waiting, vaccinating
Pediatricians know that many children with ear infections will get better without antibiotics. “Parents should know that their doctor may suggest watching an ear infection without antibiotics, as is the recommendation from the AAP,” Dr. Cosimini said.
Data indicate that doctors are not following this practice as often as they could be, he said.
When antibiotic treatment is needed during the shortage, agents other than amoxicillin suspension can be used.
“Even though amoxicillin suspension is our go-to antibiotic for many infections, there are effective alternative options,” Dr. Cosimini said. “Children’s Hospital of Philadelphia has a good list for doctors looking for alternatives.”
Another approach to reducing the use of antibiotics in the future involves preventing infections through vaccination.
Research shows that routine childhood vaccines may have averted millions of respiratory and ear infections. And because bacterial infections can follow viral infections, the annual flu vaccine and COVID-19 vaccines “are also great tools to reduce antibiotic use,” Dr. Cosimini said.
A turn to more toxic options?
The shortage of amoxicillin oral powder for suspension was reported by the Food and Drug Administration and the American Society of Health-System Pharmacists (ASHP) in October.
On Nov. 4, the Society of Infectious Diseases Pharmacists (SIDP) issued a statement on the amoxicillin shortage, noting that increased demand for the drug coincided with a surge in respiratory viral infections, including RSV and influenza, among children.
“Though supportive care is the mainstay of treatment for viral infections, antibiotics may be indicated for the treatment of superimposed bacterial infections, including pneumonia and acute otitis media,” the SIDP statement said. “While alternative antibiotics may be available depending on the indication, many have a broader spectrum of activity, increased toxicity, and excess cost relative to amoxicillin. Furthermore, it is anticipated alternatives may soon become in short supply as well, given increased usage.”
SIDP “encourages the judicious use of antibiotics” and supports watch-and-wait strategies and the use of the shortest effective duration of therapy when appropriate.
Michael Ganio, PharmD, senior director of pharmacy practice and quality for ASHP, monitors around 250 drug shortages at any given time.
The amoxicillin shortage, while not “overly worrisome,” stands out because of how widely the drug is used and the fact that the shortage appears to have been sparked by an increase in demand rather than supply chain or manufacturing quality problems that more typically lead to shortages, he said.
Unlike some other shortages, the amoxicillin shortfall largely does not involve disrupting a medication regimen that someone was already receiving, and substitutions should be available.
“That said, it’s very, very disruptive to parents or a caregiver when you have a sick child who needs an antibiotic and it’s not available,” Dr. Ganio said.
Can a poster change practice?
In an unrelated move, the U.S. Agency for Healthcare Research and Quality published new resources and strategies to reduce inappropriate antibiotic use in ambulatory care settings.
One of the tools is a poster that doctors can print and hang in their offices. It states: “We commit to only prescribing antibiotics when they will help you. Taking antibiotics when you do not need them will NOT make you better. You will still feel sick, and the antibiotic may give you a skin rash, diarrhea, or a yeast infection.”
Jeffrey A. Linder, MD, MPH, a general internist and researcher at Northwestern University in Chicago, helped develop some of the approaches to improve prescribing practices in primary care.
Dr. Linder explained on a recent episode of the Freakonomics, M.D. podcast that the poster can be key.
One reason clinicians may prescribe antibiotics inappropriately is because they assume – perhaps erroneously – that patients want and expect them. By addressing the issue up front by displaying the poster, they may be able to “short-circuit” that type of thinking.
A minority of patients do expect antibiotics. “But the vast majority of patients are thinking, ‘I don’t feel well, I want to know what’s going on, and I want to know how to feel better and what’s going to happen.’ ”
For their part, patients can tell their doctors that they want an antibiotic only if they really need it, Dr. Linder said.
A version of this article first appeared on Medscape.com.
Promising new antibiotic emerges for treating UTIs
A new antibiotic for urinary tract infections is heading toward government approval.
It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.
Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.
There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.
“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.
However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.
The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.
“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.
A version of this article first appeared on Medscape.com.
A new antibiotic for urinary tract infections is heading toward government approval.
It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.
Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.
There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.
“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.
However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.
The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.
“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.
A version of this article first appeared on Medscape.com.
A new antibiotic for urinary tract infections is heading toward government approval.
It would be the first new treatment in 20 years for UTIs, which affect more than half of women at least sometime in their lives, according to data compiled by the Department of Health and Human Services.
Called Gepotidacin, the antibiotic’s trial has halted enrollment early due to excellent effectiveness and safety results thus far, drugmaker GSK announced in a press release Nov. 3. GSK will seek approval and peer-reviewed publication early next year.
There is a need for new antibiotics such as this because of increasing antibiotic resistance. Antibiotic resistance to bacteria has become so prevalent that the World Health Organization recently began publishing a list of bacteria that pose the greatest public health threats.
“It’s definitely a big deal,” Cindy Liu, MD, MPH, PhD, of the Antibiotic Resistance Action Center at George Washington University, told CNN.
However, antibiotics are not a particularly profitable type of drug, The Wall Street Journal reported. The newspaper noted that they need to be used sparingly to limit resistance, and the cheapest option is usually prescribed. Some small companies that make antibiotics have even gone bankrupt recently, the Journal noted.
The U.S. government has invested in GSK’s development of Gepotidacin. The company predicts the drug could be a “blockbuster” and earn more than $1 billion due to UTI resistance to other drugs, the Journal reported.
“I think it will be really interesting and important to the field to see both how the drug companies sort of market this product and sort of how it does,” Dr. Liu said.
A version of this article first appeared on Medscape.com.
Oral FMT on par with colonic FMT for recurrent C. difficile
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A real-world analysis confirms that fecal microbiota transplantation (FMT) is highly effective for recurrent Clostridioides difficile infection (rCDI) – and there is no difference between delivery by capsule (cap-FMT) and colonoscopy (colo-FMT).
“We present one of the largest cohorts involving people who received capsule FMT. Byron Vaughn, MD, with the division of gastroenterology, hepatology, and nutrition, University of Minnesota, Minneapolis, said in an interview.
The study was published online in Clinical Gastroenterology and Hepatology.
The Food and Drug Administration allows FMT to be used for patients who have failed standard treatment for rCDI under a policy of enforcement discretion.
The past decade has seen an increase in the use of FMT in clinical practice, owing to an increase in cases of rCDI after failure of standard antibiotic therapy.
Unlike antibiotics, which perpetuate and worsen intestinal dysbiosis, FMT restores the diversity and function of host microbiota, effectively breaking the cycle of rCDI, the authors of the study noted. But it’s been unclear whether the efficacy and safety of FMT vary by route of administration.
Effective without procedural risks
To investigate, Dr. Vaughn and colleagues evaluated clinical outcomes and adverse events in 170 patients with rCDI who underwent cap-FMT and 96 peers who underwent colo-FMT.
FMT was performed using one of two standardized formulations of microbiota manufactured by the University of Minnesota microbiota therapeutics program: freeze-dried/encapsulated or frozen-thawed/liquid.
Overall, the cure rates of CDI were 86% at 1 month and 81% at 2 months. There was no statistically significant difference at either time between cap-FMT and colo-FMT.
The 1-month cure rate was 84% with cap-FMT and 91% with colo-FMT; at 2 months, the cure rates were 81% and 83%, respectively.
Cap-FMT has a safety and effectiveness profile similar to that of colo-FMT, without the procedural risks of colonoscopy, the researchers concluded.
They cautioned that, although FMT is highly effective overall, patient selection is a key factor to optimizing FMT success.
Older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression.
“These risk factors can help determine if a patient should receive FMT or an alternative therapy for rCDI. This is not to say FMT should be avoided in older patients or those on dialysis, but clinicians should be aware of these associations in light of other options for rCDI,” Dr. Vaughn said.
Confirming prior studies, antibiotic use after FMT was a major factor in its failure. Patient selection for FMT should include an assessment of the potential need for antibiotics after transplant, the researchers noted.
One serious adverse event (aspiration pneumonia) was related to colonoscopy; otherwise, no new safety signals were identified.
As reported in other studies, changes in bowel function, including diarrhea, constipation, gas, and bloating were common, although it’s tough to disentangle gastrointestinal symptoms related to FMT from those after CDI, the researchers said. Importantly, no transmission of an infectious agent related to FMT was identified.
Two good options
The researchers said their findings are “highly generalizable” because the population reflects all FMT use by participating institutions and contains a mix of academic centers and private practices.
Many patients included in the study would not have been eligible for a clinical trial, owing to their having many comorbid conditions, including immune compromise and inflammatory bowel disease, the authors noted.
“FMT is recommended by major gastroenterology and infectious disease society guidelines,” Dr. Vaughn said. “Our group, and others, have consistently found strategies that incorporate FMT as cost-effective strategies for treating rCDI.”
However, lack of access to FMT products often is a barrier to treatment, he said.
“A stool banking model, similar to the nonprofit blood banking model, may be a useful solution to ensure equitable access to FMT to all who need it,” Dr. Vaughn added.
Reached for comment, Majdi Osman, MD, MPH, told this news organization that the study is valuable, “as it nicely shows in a real-world setting that capsules and colonoscopy are good options for patients who need this.”
Dr. Osman is chief medical officer of OpenBiome, a nonprofit organization that operates a public stool bank and is the major FMT source in the United States. The organization has provided over 63,000 FMT treatments to over 1,200 hospitals in the United States.
“FMT has become standard of care for patients who failed antibiotic therapy, and certainly is being used widely as a treatment option for these patients who have often run out of existing options,” Dr. Osman said.
Support for the study was provided by a donation from Achieving Cures Together, a nonprofit organization dedicated to advancing microbiome-based research. Dr. Vaughn receives grant support from Takeda, Roche, Celgene, and Diasorin and has received consulting fees from Prometheus and AbbVie. Dr. Osman reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
RBX2660 shows promise in breaking the cycle of recurrent C. difficile
CHARLOTTE, N.C. –
Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.
The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.
The study also placed no limit on the number of previous rounds of C. difficile infections.
“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.
“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.
Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
Study design and results
RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.
After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.
The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.
At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.
Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.
Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.
“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.
For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
Adverse events
Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.
“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”
Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.
The serious adverse events “were very, very few,” Dr. Khanna said.
Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
“Excruciating for patients to deal with”
Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.
However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”
“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.
Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.
But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.
Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.
Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.
“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
FDA advisory committee nod
On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.
Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.
The FDA often follows its advisory committee recommendations but is not required to do so.
“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.
The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHARLOTTE, N.C. –
Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.
The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.
The study also placed no limit on the number of previous rounds of C. difficile infections.
“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.
“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.
Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
Study design and results
RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.
After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.
The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.
At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.
Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.
Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.
“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.
For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
Adverse events
Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.
“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”
Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.
The serious adverse events “were very, very few,” Dr. Khanna said.
Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
“Excruciating for patients to deal with”
Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.
However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”
“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.
Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.
But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.
Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.
Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.
“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
FDA advisory committee nod
On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.
Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.
The FDA often follows its advisory committee recommendations but is not required to do so.
“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.
The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHARLOTTE, N.C. –
Following a standard course of antibiotics, a one-time treatment with RBX2660 was successful for three quarters of participants at 8 weeks, according to a new study. It also prevented additional bouts, with 84% of these initial responders remaining free of C. difficile infection at 6 months.
The ongoing phase 3, open-label PUNCH CD3-OLS study expands on clinical trial experience by treating more “real-world” patients. People who might have been excluded from previous research because of comorbidities, such as irritable bowel syndrome, inflammatory bowel disease, and immunosuppression, were included.
The study also placed no limit on the number of previous rounds of C. difficile infections.
“Even when you expand the patient population to make it more generalizable, we’re still seeing both a high cure rate and a high success rate,” Sahil Khanna, MBBS, a gastroenterologist and hepatologist at the Mayo Clinic in Rochester, Minn., said in an interview.
“We also are not seeing any kind of safety signals that can be attributed to this particular product,” he said.
Dr. Khanna presented the findings during the annual meeting of the American College of Gastroenterology, which were also published simultaneously in the journal Drugs. The research by Dr. Khanna and associates received an ACG Outstanding Research Award in the colon category.
Study design and results
RBX2660 (Rebyota) is a microbiota-based live biotherapeutic in development from Ferring Pharmaceuticals. The treatment contains human stool collected from prescreened, qualified donors and is prepared according to good manufacturing standards.
After standard-of-care antibiotics and a 72-hour washout period, participants received a single 150-mL dose rectally by enema. RBX2660 is administered by a health care professional.
The median age of study participants was 63 years, with 45% aged 65 years or older, and 70% were women. Overall, 37% of participants had Crohn’s disease and 4% had ulcerative colitis.
At the time of screening, about half of participants had a history of one or two infections with C. difficile, and the remaining half reported three or more episodes.
Of the 402 participants whose outcomes could be analyzed, 75% reported treatment success, meaning no further C. difficile infections at 8 weeks. This was consistent with the 75% of 60 participants free of C. difficile in the interim analysis reported in 2021. Efficacy results were based on a modified intent-to-treat analysis.
Of the 300 participants who responded to RBX2660 at 8 weeks, 262 were followed up to 6 months, with 84% of these reporting no C. difficile recurrence.
“If you succeeded to 8 weeks, there was a high likelihood that you would succeed up to 6 months,” Dr. Khanna said.
For the subset of participants with inflammatory bowel disease, Dr. Khanna noted that the success rates were in the 80% range, which is higher than what is seen in clinic fecal microbiota transplantation programs.
Adverse events
Of the participants, 63% reported treatment-emergent adverse events. Most events were mild to moderate in severity, the researchers reported, with diarrhea and abdominal pain being the most common.
“When you look at the treatment-emergent adverse events, it’s important to put them into context in terms of this patient population,” Dr. Khanna said. “This recurrent population has developed underlying gastrointestinal symptoms like abdominal pain, diarrhea, nausea, vomiting, and weight loss.”
Some of these adverse events persist beyond resolution of the C. difficile infection, and the adverse-event profile with RBX2660 is consistent with what is seen following fecal microbiota transplantation, he added.
The serious adverse events “were very, very few,” Dr. Khanna said.
Overall, 11% of participants reported a serious adverse event. The majority were related to the C. difficile infection or an underlying comorbidity, he noted.
“Excruciating for patients to deal with”
Traditionally, there could be “some hesitation on the patient’s part [to undergo therapy] just because it’s delivered rectally,” session comoderator Lisa Malter, MD, said in an interview.
However, C. difficile can be “excruciating for patients to deal with,” said Dr. Malter, a gastroenterologist and professor of medicine at New York University Langone Health. They “may be more than willing to take [this agent] because it gets them feeling better.”
“This is a positive adjunct to our current therapies for C. diff in terms of trying to knock it out once a standard course of antibiotics has been administered,” she added.
Currently, people with recurrent C. difficile seek fecal microbiota material from a biobank or from a close friend or loved one.
But Dr. Malter noted that asking someone you know to donate fecal matter for transplantation requires several steps. Donors are screened to make sure they are free of gastrointestinal illness, are not taking any contraindicated medications, and do not have active infection.
Fecal microbiota samples from a biobank are more standardized, but there have been intermittent shutdowns and availability has been limited during the pandemic, she said.
Dr. Malter added that one unanswered question is how much of the colon is covered by therapy delivery via enema compared with colonoscope delivery during fecal microbiota transplantation.
“If it’s delivered colonoscopically, you get the entire colon. In contrast with an enema, you really only hit the left side of the colon,” she said.
FDA advisory committee nod
On Sept. 26, the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee reviewed evidence for RBX2660. The committee voted 13 to 4 that data were adequate to support the effectiveness of RBX2660 to reduce the recurrence of C. difficile infection in adults following antibiotic treatment for recurrent infections.
Members also voted 12 to 4, with one abstention, that the data were adequate to support the product’s safety.
The FDA often follows its advisory committee recommendations but is not required to do so.
“The hope would be that this would get through the usual FDA pipeline of an approval in the near future,” Dr. Khanna said.
The study was funded by Ferring Pharmaceuticals. Dr. Khanna reported receiving grant and research funding from Ferring. Dr. Malter reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2022
FMT in IBS: ‘We’ve been targeting the wrong part of the intestine’
VIENNA – , vs. it being administered into the large intestine, according to a new study.
Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.
“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.
Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.
“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.
“Until now, we’ve been targeting the wrong part of the intestine,” he said.
The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.
Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.
Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.
“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”
In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
Targeting the small intestine
FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.
In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.
A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.
Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.
The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.
Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.
At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.
At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.
By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).
Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.
“Long-term side effects, as monitored up to 3 years, were not observed,” he added.
Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.
Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.
Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
Location affects bacterial success
Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.
Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.
“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”
“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
Broader questions
“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”
FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.
“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”
The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.
“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.
Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.
“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.
Drug distribution data are needed to determine host-microbiota interactions.
“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.
Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.
A version of this article first appeared on Medscape.com.
VIENNA – , vs. it being administered into the large intestine, according to a new study.
Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.
“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.
Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.
“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.
“Until now, we’ve been targeting the wrong part of the intestine,” he said.
The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.
Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.
Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.
“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”
In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
Targeting the small intestine
FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.
In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.
A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.
Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.
The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.
Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.
At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.
At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.
By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).
Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.
“Long-term side effects, as monitored up to 3 years, were not observed,” he added.
Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.
Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.
Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
Location affects bacterial success
Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.
Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.
“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”
“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
Broader questions
“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”
FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.
“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”
The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.
“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.
Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.
“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.
Drug distribution data are needed to determine host-microbiota interactions.
“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.
Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.
A version of this article first appeared on Medscape.com.
VIENNA – , vs. it being administered into the large intestine, according to a new study.
Patients also reported an improvement in symptoms and quality of life with repeated doses of FMT (two doses, given 1 week apart), compared with a single dose in the small intestine, although statistical significance was not met.
“Administering a fecal transplant to the small intestine leads to long-term – up to 1 year in this analysis – colonization of beneficial bacteria, whereas administrating the fecal transplant to the large intestine results in the effect only lasting for the first 3 months,” said Magdy El-Salhy, MD, from the University of Bergen, Norway.
Dr. El-Salhy presented the results at the annual United European Gastroenterology Week meeting.
“It seems that bacteria in the small intestine play a more central role in IBS, as well as its associated fatigue, than bacteria in the large intestine,” Dr. El-Salhy said in an interview.
“Until now, we’ve been targeting the wrong part of the intestine,” he said.
The findings are the first to show that the small intestine is a more effective location for administering FMT than the large intestine for IBS. “It would be worthwhile doing similar [studies] in other diseases, especially in inflammatory bowel diseases,” said Dr. El-Salhy.
Researchers also didn’t expect the repeated dose to improve symptoms for a longer duration. “It really was revolutionary to see,” he added.
Some of Dr. El-Salhy’s patients have had up to 5 years of follow-up, although these results were not presented at this year’s UEG, he said.
“Around 75% of my patients have shown duration of response up to 3 years, and a few up to 5 years, on a 60-g dose from an earlier study group,” he said. “It’s an incredible result after a 10-minute treatment.”
In Dr. El-Salhy’s previous work, he found that increasing the dose from 30 g to 60 g increased the response from about 75% to about 90%. However, in this study presented, he found that increasing the dose to 90 g did not further increase the response. He also noted that while repeating the FMT dose improved symptoms and quality of life more than a single transplantation, it did not increase the response.
Targeting the small intestine
FMT has been widely investigated for the treatment of such conditions as psoriatic arthritis, Clostridioides difficile infection, and ulcerative colitis.
In this study, Dr. El-Salhy built on prior work (seven randomized controlled studies with varied outcomes) by asking whether the transplant dose increases FMT efficacy, which route of administration is more effective, and whether repeating FMT increases efficacy in patients with IBS.
A total of 186 patients were randomized to one of three groups: 90 g of frozen transplant into the large intestine (n = 62), 90 g of frozen transplant into the small intestine (n = 62), or 90 g of frozen transplant into the small intestine twice (with a 1-week interval; n = 62). FMT was administered via nasoduodenal tube and colonoscopy into the small and large intestines, respectively.
Outcomes were measured at 3, 6, and 12 months. The 12-month analysis of outcomes via patient questionnaire included 60, 61, and 60 patients, respectively.
The patient questionnaires included in the study were the IBS-SSS (a composite score of abdominal pain, duration of abdominal pain, bloating/distention, satisfaction with bowel habits, and IBS-related quality of life), the Birmingham IBS Symptom questionnaire, the Fatigue Assessment Scale questionnaire, the IBS-Quality of Life assessment, and the Short-Form Nepean Dyspepsia Index.
Fecal samples were taken and tested for bacterial loads. The bacterial profile and dysbiosis index were determined using the 16S rRNA gene.
At 3 months, patients had similar response rates, around 80%, across single dose in large intestine, single dose in small intestine, and repeat doses in small intestine.
At 6 months, the differences in response rates started to become noticeable, with 67.9% for single dose in large intestine, 71.4% for single dose in small intestine, and 86% for repeat doses in small intestine.
By 12 months, the difference in response rate between the single dose in the large and small intestines was statistically significant at 51.9% and 75.5%, respectively. The response rate to the repeat doses in the small intestine at 12 months (80.9%) was similar to that at 3 months (80.8%).
Side effects, including mild abdominal pain, diarrhea, and constipation, after FMT were seen for the first 5 days after treatment. “People who generally suffer from constipation get diarrhea after FMT and vice versa,” Dr. El-Salhy reported.
“Long-term side effects, as monitored up to 3 years, were not observed,” he added.
Treatment reduced IBS symptoms in all patient groups as measured by IBS-SSS scores. By 12 months, the score fell from around 350 to around 220 in patients who received a single dose in the large intestine, from around 300 to around 200 in patients who received a single dose in the small intestine, and from around 350 to around 170 in patients who received repeat doses in the small intestine.
Quality of life showed a statistically significant difference at 3 months between single and repeated doses in the small intestine and similarly at 6 and 12 months.
Chronic fatigue, experienced by many patients with IBS, was substantially reduced after FMT, Dr. El-Salhy noted. “This surge in energy is often more important to them than the gastrointestinal symptoms.”
Location affects bacterial success
Certain beneficial bacteria were found to thrive more when the donor transplant was administered to the small intestine than to the large intestine.
Of note, Lactobacillus species and Holdemanella biformis grew and then dropped off sharply after 3 months in patients who received a single-dose fecal transplant in the large intestine, while they grew after 3 months and continued to grow after 6 and 12 months in the groups who received a fecal transplant in the small intestine.
“We think bacteria in the small intestine have different characteristics to those in the large intestine,” Dr. El-Salhy said. “This is relatively new, because many years ago it was thought that bile acids prevented bacterial survival. Now we know lots can thrive in the small intestine.”
“It might be viral or some other component that is most effective here. We don’t know yet, but so far we have identified 11 bacteria of interest,” he added.
Broader questions
“Rather than focusing on a specific, single strain microbe as a predictor of success in a disease, the global equilibrium of microbiota is more important, and microbial ecology parameters would be interesting to assess,” remarked Gianluca Ianiro, MD, from the Università Cattolica del Sacro Cuore, Rome, who comoderated the session. “Selected survival of some bacteria through the gut may be the response.”
FMT emerged in response to the challenges posed by recurrent C. difficile infections, noted Alexander Khoruts, MD, a professor of medicine in the division of gastroenterology, hepatology, and nutrition at the University of Minnesota, Minneapolis, who was not involved in the research.
“It is much harder to achieve remodeling of the gut microbiome in non–C. difficile conditions where there is an intact and resilient indigenous microbiota,” he said in an interview. “Therefore, regimens using antibiotic preconditioning and repeated administrations of microbiota are generally more efficacious in achieving this objective.”
The specificity of the bacteria according to disease type targeted was important, said Dr. Khoruts, who has a special interest in gut microbiota.
“The big question in non–C. difficile indications is the composition of donor microbiota. It is critical that we understand the mechanisms involved in each target disease to design appropriate microbiota-based therapeutics,” he said.
Dr. Khoruts sounded a note of caution with respect to establishing the pharmacokinetic and dynamic data related to FMT, which is classified as a drug in the United States.
“It’s imperative that we develop the pharmacology discipline appropriate for this class of therapeutics, including their pharmacokinetics and pharmacodynamics, and an understanding of their potential toxicity and drug-drug interactions,” he said.
Drug distribution data are needed to determine host-microbiota interactions.
“This includes the small bowel microbiome, which continues to be woefully understudied,” Dr. Khoruts said.
Dr. El-Salhy reports no relevant financial relationships. Dr. Ianiro reports receiving personal fees for acting as speaker for Biocodex, Sofar, Malesci, and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Biocodex, Tillotts Pharma, and Zambon. Dr. Khoruts reports he has patents pertaining to fecal microbiota separation from stool and their cryopreservation and lyopreservation.
A version of this article first appeared on Medscape.com.
AT UEG WEEK 2022
Limiting antibiotic overprescription in pandemics: New guidelines
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
A statement by the Society for Healthcare Epidemiology of America, published online in Infection Control & Hospital Epidemiology, offers health care providers guidelines on how to prevent inappropriate antibiotic use in future pandemics and to avoid some of the negative scenarios that have been seen with COVID-19.
According to the U.S. Centers of Disease Control and Prevention,
The culprit might be the widespread antibiotic overprescription during the current pandemic. A 2022 meta-analysis revealed that in high-income countries, 58% of patients with COVID-19 were given antibiotics, whereas in lower- and middle-income countries, 89% of patients were put on such drugs. Some hospitals in Europe and the United States reported similarly elevated numbers, sometimes approaching 100%.
“We’ve lost control,” Natasha Pettit, PharmD, pharmacy director at University of Chicago Medicine, told this news organization. Dr. Pettit was not involved in the SHEA study. “Even if CDC didn’t come out with that data, I can tell you right now more of my time is spent trying to figure out how to manage these multi-drug–resistant infections, and we are running out of options for these patients,”
“Dealing with uncertainty, exhaustion, [and] critical illness in often young, otherwise healthy patients meant doctors wanted to do something for their patients,” said Tamar Barlam, MD, an infectious diseases expert at the Boston Medical Center who led the development of the SHEA white paper, in an interview.
That something often was a prescription for antibiotics, even without a clear indication that they were actually needed. A British study revealed that in times of pandemic uncertainty, clinicians often reached for antibiotics “just in case” and referred to conservative prescribing as “bravery.”
Studies have shown, however, that bacterial co-infections in COVID-19 are rare. A 2020 meta-analysis of 24 studies concluded that only 3.5% of patients had a bacterial co-infection on presentation, and 14.3% had a secondary infection. Similar patterns had previously been observed in other viral outbreaks. Research on MERS-CoV, for example, documented only 1% of patients with a bacterial co-infection on admission. During the 2009 H1N1 influenza pandemic, that number was 12% of non–ICU hospitalized patients.
Yet, according to Dr. Pettit, even when such data became available, it didn’t necessarily change prescribing patterns. “Information was coming at us so quickly, I think the providers didn’t have a moment to see the data, to understand what it meant for their prescribing. Having external guidance earlier on would have been hugely helpful,” she told this news organization.
That’s where the newly published SHEA statement comes in: It outlines recommendations on when to prescribe antibiotics during a respiratory viral pandemic, what tests to order, and when to de-escalate or discontinue the treatment. These recommendations include, for instance, advice to not trust inflammatory markers as reliable indicators of bacterial or fungal infection and to not use procalcitonin routinely to aid in the decision to initiate antibiotics.
According to Dr. Barlam, one of the crucial lessons here is that if clinicians see patients with symptoms that are consistent with the current pandemic, they should trust their own impressions and avoid reaching for antimicrobials “just in case.”
Another important lesson is that antibiotic stewardship programs have a huge role to play during pandemics. They should not only monitor prescribing but also compile new information on bacterial co-infections as it gets released and make sure it reaches the clinicians in a clear form.
Evidence suggests that such programs and guidelines do work to limit unnecessary antibiotic use. In one medical center in Chicago, for example, before recommendations on when to initiate and discontinue antimicrobials were released, over 74% of COVID-19 patients received antibiotics. After guidelines were put in place, the use of such drugs fell to 42%.
Dr. Pettit believes, however, that it’s important not to leave each medical center to its own devices. “Hindsight is always twenty-twenty,” she said, “but I think it would be great that, if we start hearing about a pathogen that might lead to another pandemic, we should have a mechanism in place to call together an expert body to get guidance for how antimicrobial stewardship programs should get involved.”
One of the authors of the SHEA statement, Susan Seo, reports an investigator-initiated Merck grant on cost-effectiveness of letermovir in hematopoietic stem cell transplant patients. Another author, Graeme Forrest, reports a clinical study grant from Regeneron for inpatient monoclonals against SARS-CoV-2. All other authors report no conflicts of interest. The study was independently supported.
A version of this article first appeared on Medscape.com.
FROM INFECTION CONTROL & HOSPITAL EPIDEMIOLOGY
Antibiotic-resistant bacteria emerging in community settings
A new study from the Centers for Disease Control and Prevention found that
Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.
CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.
Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.
But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”
CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.
The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).
Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”
Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”
This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”
Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”
This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.
But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.
Ms. Bulens and Dr. Price reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study from the Centers for Disease Control and Prevention found that
Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.
CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.
Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.
But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”
CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.
The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).
Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”
Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”
This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”
Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”
This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.
But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.
Ms. Bulens and Dr. Price reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A new study from the Centers for Disease Control and Prevention found that
Traditionally, CRE has been thought of as a nosocomial infection, acquired in a hospital or other health care facility (nursing home, long-term acute care hospital, dialysis center, etc.). This is the first population-level study to show otherwise, with fully 10% of the CRE isolates found to be community acquired.
CREs are a group of multidrug-resistant bacteria considered an urgent health threat by the CDC because they can rapidly spread between patients, especially those who are most seriously ill and vulnerable, and because they are so difficult to treat. These patients often require treatment with toxic antibiotics, such as colistin, and carry a high mortality rate – up to 50% in some studies.
Overall, 30% of CREs carry a carbapenemase – an enzyme that can make them resistant to carbapenem antibiotics. The genes for this are readily transferable between bacteria and help account for their spread in hospitals.
But in this study, published in the American Journal of Infection Control, of the 12 isolates that underwent whole-genome sequencing, 42% of the CA-CRE isolates carried the carbapenemase gene. Lead author Sandra Bulens, MPH, a health scientist in the CDC’s division of health care quality promotion, said in an interview, “The findings highlight the potential for CP-CRE to move from health care settings into the community. The fact that 5 of the 12 isolates harbored a carbapenemase gene introduces new challenges for controlling spread of CP-CRE.”
CDC researchers analyzed data from eight U.S. metropolitan areas between 2012 and 2015 as part of the CDC’s Emerging Infections Program (EIP) health care–associated infections – community interface activity, which conducts surveillance for CRE and other drug-resistant gram-negative bacteria. Cases of CA-CRE were compared with HCA-CRE, with 1499 cases in 1,194 case-patients being analyzed. Though Klebsiella pneumoniae was the most common isolate, there were some differences between metropolitan areas.
The incidence of CRE cases per 100,000 population was 2.96 (95% confidence interval, 2.81-3.11) overall and 0.29 (95% CI, 0.25-0.25) for CA-CRE. Most CA-CRE cases were in White persons (73%) and women (84%). Urine cultures were the source of 98% of all CA-CRE cases, compared with 86% of HCA-CRE cases (P < .001). Though small numbers, the numbers of patients with CA-CRE without apparent underlying medical condition (n = 51; 37%) was greater when compared with patients with HCA-CRE (n = 36; 3%; P < .001).
Asked for independent comment, Lance Price, PhD, of George Washington University and the founding director of GW’s Antibiotic Resistance Action Center, Washington, said, “what’s striking about these data is that: ‘Who is the front line, at least in the United States for CRE?’ It’s women, older women. ... At some point, we have to frame drug resistance as a women’s health issue.”
Dr. Price noted that the 10% of patients with CA-CRE acquired it in the community. “I would argue that probably none of them had any idea, because there’s this silent community epidemic,” he said. “It’s asymptomatic carriage and transmission in the community. Somebody can be this walking reservoir of these really dangerous bacteria and have no idea.”
This is an increasingly serious problem for women, Dr. Price said, because, “with a community-acquired bladder infection, you’re going to call your doctor or go to an urgent care, and they’re not going to test you. They’re going to guess what you have, and they’re going to prescribe an antibiotic, and that antibiotic is going to fail. So then your bladder infection continues, and then you wait a few more days, and you start to get flank pain and kidney infection. ... If you start getting a fever, they might admit you. They are going to start treating you immediately, and they might miss it because you’ve got this organism that’s resistant to all the best antibiotics. ... The gateway to the blood is the UTI.”
Because of such empiric treatment and increasing resistance, the risk for treatment failure is quite high, especially for older women. Ms. Bulens, however, said that, “[although] 10% of CRE were in persons without health care risk factors, the proportion of all UTIs in this population that are CRE is going to be very, very small.”
This study involved cultures from 2012 to 2015. Before the pandemic, from 2012 to 2017, U.S. deaths from antibiotic resistance fell by 18% overall and by 30% in hospitals.
But in the first year of the COVID-19 pandemic, there was a 15% increase in infections and deaths from antibiotic-resistant (AMR), hospital-acquired bacteria. In 2020, 29,400 patients died from AMR infections. There was a 78% increase in carbapenem-resistant Acinetobacter baumannii health care–associated infections, a 35% increase in carbapenem-resistant Enterobacterales, and 32% increases in both multidrug-resistant Pseudomonas aeruginosa and extended-spectrum beta-lactamase–producing Enterobacterales. Aside from gram-negative bacteria, methicillin-resistant Staphylococcus aureus rose 13%, and Candida auris rose 60%. But owing to limited surveillance, recent sound figures are lacking.
Ms. Bulens and Dr. Price reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF INFECTION CONTROL
Typhoid fever bacteria becoming more resistant to antibiotics
Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.
Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.
Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.
Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
Global deaths: 100,000 annually
Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.
The findings are further evidence of the need for a global response, the authors write.
Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.
“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.
He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”
Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.
Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.
Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
Only one oral option left in Pakistan
“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.
Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”
Moreover, some resistant strains from Pakistan have been turning up in the United States.
“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.
Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.
Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.
“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.
Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.
At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.
The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”
According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.
However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.
The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.
But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.
The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.
Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.
Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.
Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
Global deaths: 100,000 annually
Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.
The findings are further evidence of the need for a global response, the authors write.
Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.
“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.
He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”
Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.
Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.
Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
Only one oral option left in Pakistan
“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.
Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”
Moreover, some resistant strains from Pakistan have been turning up in the United States.
“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.
Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.
Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.
“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.
Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.
At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.
The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”
According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.
However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.
The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.
But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.
The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Bacteria that cause typhoid fever are becoming increasingly resistant to common antibiotics worldwide, a new analysis indicates.
Resistant strains of Salmonella enterica serovar typhi – almost all originating in South Asia – have spread across borders nearly 200 times since 1990.
Until now, analysis has been limited by small samples. This genome analysis is the largest to date and included 3,489 newly sequenced isolates (collected between 2014 and 2019) from prospective surveillance studies in four of the countries with the highest typhoid burden: Bangladesh, Nepal, Pakistan, and India.
Findings of the study, led by Kesia Esther da Silva, PhD, with the division of infectious diseases and geographic medicine at Stanford (Calif.) University, were published online in The Lancet Microbe.
Global deaths: 100,000 annually
Typhoid fever remains a global public health threat, causing 11 million infections and more than 100,000 deaths each year. Most cases (70%) are in South Asia, but typhoid also has significant presence in sub-Saharan Africa, Southeast Asia, and Oceania.
The findings are further evidence of the need for a global response, the authors write.
Jason Andrews, MD, a coauthor and associate professor in the division of infectious diseases and geographic medicine at Stanford University, said in an interview that the research helps pinpoint where the highest burden is and where the biggest need is for the two highly effective typhoid vaccines.
“We’re seeing higher levels of resistance than we’ve ever seen before against our latest and greatest antibiotics,” he said.
He said so far, strategies for tackling typhoid have involved country-level decisions and local funding and that needs to be shifted to a global priority. “Given contemporary travel migration patterns, what we see is that when antimicrobial resistance develops in one country, it quickly spreads to other countries.”
Dr. Andrews said the United States sees about 300-500 typhoid cases a year. “About 80% of those cases involve people traveling from South Asia,” he said.
Infections also come from people from the United States visiting high-burden countries, especially to see family. Often they don’t perceive the risk and skip vaccination, he said. U.S. clinicians can help with educating patients traveling to typhoid-endemic regions on pretravel vaccination.
Physician awareness is also important when patients have recently returned from such regions. Data from this study show a need to carefully consider which antibiotics will be effective with the growing resistance.
Only one oral option left in Pakistan
“We are running low on treatment options for typhoid,” Dr. Andrews said. The resistance pattern in Pakistan, for example, has left only one oral option, azithromycin, and resistance is building to that.
Without that option, “we’ll have to hospitalize patients and give intravenous antibiotics,” he said. “That’s concerning.”
Moreover, some resistant strains from Pakistan have been turning up in the United States.
“There are actually some cases that have not been tracked at all to travelers going to Pakistan and are thought to be from local transmission in the United States,” he said.
Valida Bajrovic, MD, assistant professor of medicine in infectious diseases at the Icahn School of Medicine at Mount Sinai, New York, said in an interview that, in addition to vaccinating travelers before they head to typhoid-endemic areas, physicians should educate patients on avoiding fecal transmission of typhoid with vigilant hand washing, drinking bottled water, and avoiding foods that may have been prepared in unsanitary conditions.
Dr. Bajrovic, who directs the antimicrobial stewardship efforts at the Mount Sinai Morningside and Mount Sinai West Hospitals, said stricter antimicrobial stewardship efforts are needed, particularly in Europe and South Asia, but also in the United States.
“Restriction of antibiotic use is the way to prevent antibiotic resistance,” she said, adding that such restrictions need to be part of a global effort.
Strains in the study were classified as multidrug resistant (MDR) if they contained genes resistant to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole. The authors also traced the presence of genes demonstrating resistance to macrolides and quinolones.
At first, fluoroquinolones were effective against MDR S. typhi and in the 1990s became the primary therapy. By the 2010s, however, the majority of S. typhi in south Asia contained mutations in the quinolone resistance-determining regions.
The authors wrote: “We found evidence of frequent international (n = 138) and intercontinental transfers (n = 59) of antimicrobial-resistant S. typhi.”
According to the analysis, since 2000, MDR S. typhi has declined steadily in Bangladesh and India and remained at less than 5% of typhoid strains in Nepal, though it has increased slightly in Pakistan.
However, these are being replaced “with strains containing ceftriaxone resistance (extensively drug resistant), high-level fluoroquinolone resistance, or azithromycin resistance, which are reversing declines in the effective population size of S. typhi,” the authors wrote.
The analysis supports urgency for prevention measures, including use of typhoid conjugate vaccines in typhoid-endemic countries, the authors said.
But given the rise in international spread of increasingly resistant strains, they said, preventive measures should not be limited to those countries.
The study was funded by the Bill & Melinda Gates Foundation. Dr. Da Silva, Dr. Andrews, and Dr. Bajrovic have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Precision medicine vs. antibiotic resistance
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.