Antimicrobial-resistant infections

CHARLOTTE, N.C. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

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. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

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. – RBX2660 could be a new option for people who experience recurrent, debilitating Clostridioides difficile infections.

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.

VIENNA – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), 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 – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), 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 – Fecal microbiota transplantation (FMT) into the small intestine led to a better response rate of longer duration in patients with irritable bowel syndrome (IBS), 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.

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 COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

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 COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

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 COVID-19 pandemic brought an alarming increase in antimicrobial resistance in hospitals, with infections and deaths caused by resistant bacteria and fungi going up by 15%. For some pathogens, such as the Carbapenem-resistant Acinetobacter, that number is now as high as 78%.

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 new study from the Centers for Disease Control and Prevention found that a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

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 a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

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 a surprising proportion of cases of carbapenem-resistant Enterobacterales (CRE) are found in isolates from patients in the community (CA-CRE). They had previously been thought to be health care–associated infections (HCA-CRE).

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.

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.

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.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.

“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.

This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.

“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.

Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.

In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.

She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
 

A ‘huge infectious burden’

If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.

“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.

“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.

While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”

Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”

If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.

Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”

Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.

“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.

This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.

“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.

Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.

In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.

She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
 

A ‘huge infectious burden’

If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.

“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.

“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.

While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”

Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”

If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.

Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”

Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

An investigational, novel oral antibiotic with greater selectivity than vancomycin, metronidazole, and even fidaxomicin may offer improved protection of healthy gut bacteria during the treatment of Clostridium difficile infection (CDI), according to ongoing research.

“CDI treatment has historically been dominated by metronidazole and vancomycin,” said Katherine Johnson, DO, from the Western Infectious Disease Consultants, P.C., Denver. However, these broad-spectrum drugs negatively affect healthy bacteria in the gut and increase the risk of CDI recurrence.

This is also a problem for drugs in the CDI antibiotic pipeline: Many candidate drugs have failed because of their broad-spectrum activity, she added during a session at the Peggy Lillis Foundation 2022 National C. diff. Advocacy Summit.

“An ideal CDI therapy would be a very narrow-spectrum antibiotic that has a minimal effect on normal gut bacteria,” she said.

Dr. Johnson is currently working on a phase 2 clinical trial that is evaluating the novel antibiotic, dubbed CRS3123, for the treatment of primary CDI and first-recurrence CDI. The investigational agent targets and inhibits a form of the methionyl tRNA synthetase enzyme, which is strictly required for protein biosynthesis in C. diff. and is therefore an ideal target for treatment of primary and recurrent CDI.

In her session, Dr. Johnson reported that CRS3123 inhibits the damaging toxins produced by C. diff., potentially resulting in more rapid symptom resolution. Additionally, owing to its novel mode of action, no strains are currently resistant to CRS3123.

She presented findings from an animal study that showed that CRS3123 was superior to vancomycin in terms of prolonging survival. She also presented findings from phase 1 clinical trials that showed that most adverse events (AEs) associated with CRS3123 were mild. No serious AEs were reported.
 

A ‘huge infectious burden’

If successful in further research, CRS3123 could offer significant value to patients with C. diff., especially those with recurrent infection, given the sometimes extreme clinical, quality-of-life, and economic burdens associated with CDI.

“CDI is a huge infectious burden to the U.S. health care system and globally has been listed by the Centers for Disease Control and Prevention as an urgent threat,” Byron Vaughn, MD, from the University of Minnesota, told this news organization.

“Despite a number of antibiotic stewardship and infection control and prevention efforts, we haven’t seen much of a change in the incidence of CDI,” he said. He said that the risk of recurrence can be as high as 30%.

While oral vancomycin is effective for treating C. diff., Dr. Vaughn noted that the antibiotic lacks selectivity and destroys healthy gut bacteria, resulting in substantial dysbiosis. “Dysbiosis is really the key to getting recurrent C. diff.,” he explained, “because if you have healthy gut bacteria, you will inherently resist CDI.”

Dr. Vaughn stated that his center is in the startup phase for being a site for a clinical trial of CRS3123. The hope is that CRS3123, because its spectrum is narrower than that of fidaxomicin and vancomycin, doesn’t induce intestinal dysbiosis. “It really just treats the C. diff. and leaves every other bug alone so that your gut bacteria can recover while the C. diff. is being treated,” he said. “And then when you stop CRS3123, you have healthy gut bacteria already present to prevent recurrence.”

If this is confirmed in large-scale trials, there could be a “dramatic decrease” in the rates of recurrent C. diff., said Dr. Vaughn.

Aside from the potential clinical impact, the economic implications of a novel selective antibiotic that preserves healthy gut bacteria could be significant, he added. “Depending on exactly what population you’re looking at, probably about a third of the cost of C. diff. is actually attributable to recurrence. That’s a huge economic burden that could be improved.”

Dr. Johnson is an employee of Crestone, which is developing CRS3123. Dr. Vaughn reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

Is fear of missing an infection – call it “FOMI” – leading you to overprescribe antibiotics to your patients?   

Inappropriate use of antibiotics can result in adverse events and toxicity, superinfections such as Clostridioides difficile and Methicillin-resistant Staphylococcus aureus, excess mortality and costs, and resistance to the drugs.   

All that has been well-known for years, and antibiotic resistance has become a leading public health concern. So why are physicians continuing to overprescribe the drugs?

Speaking at the 2022 annual Internal Medicine Meeting of the American College of Physicians, James “Brad” Cutrell, MD, medical director of antimicrobial stewardship, University of Texas Southwestern Medical Center, Dallas, said clinicians in the United States and elsewhere appear to be falling into a three-part fallacy when it comes to using the drugs: fear of “missing an infection,” coupled with patient expectations that they will leave the office with a prescription and combined with an overemphasis on the potential benefit to the individual at the expense of the risk to society of antibiotic resistance.

Antibiotics are the only drugs that lose their efficacy for all patients over time the more they are used. “For example, if I give a beta blocker to a patient, it’s not going to affect other patients down the road,” Dr. Cutrell said. “It’s not going to lose its efficacy.”

“What we need in medicine is a new culture around antibiotic use,” Dr. Cutrell added. “We need more respect for the dangers of antibiotic misuse and to have confidence in [their] benefits and when they can be used wisely.”
 

Rampant misuse

Outpatient prescriptions account for at least 60% of antibiotic use in the United States. The rate is even higher in other countries, Dr. Cutrell said during a presentation at the 2022 annual Internal Medicine Meeting of the American College of Physicians.

“About 10% of adult visits and 20% of pediatric visits will result in an antibiotic prescription,” said Dr. Cutrell, noting that prescribing patterns vary widely across the country, with as much as a three-fold difference in some locations. But at least 30% of outpatient antibiotic prescriptions are inappropriately ordered, he said.

“When we look at acute respiratory infections, upwards of 50% are not indicated at all,” he said. Imagine, he added, if the same error rate applied to other medical practices: “What if surgeons were only right 50% of the time, or if the oncologist was only giving the right treatment 50% of the time?”

The most recent Antibiotic Threats Report from the U.S. Centers for Disease Control and Prevention estimated that antibiotic-resistant bacteria and fungi cause more than 2.8 million infections and about 36,000 deaths annually in the United States alone.
 

How to be a better steward

The core elements for antimicrobial stewardship in the outpatient setting, according to Dr. Cutrell, include making a commitment to optimize prescribing, implementing at least one policy or practice to improve prescribing, monitoring prescribing practices and offering feedback to clinicians, and educating both patients and clinicians.

All that is similar to in-patient stewardship, he said, but outpatient clinicians face a few unique challenges. “Patients are lower acuity, and there is less diagnostic data, and program resources and time are more limited,” he said. Patient satisfaction is also a major driver, and it is also more difficult to measure and track ambulatory antibiotic use.

Interventions have been identified, however, that can help improve stewardship. One is auditing and feedback with peers. “Another [is] commitment posters, which can be placed around the clinic, and that helps set the culture,” he said. “Clinical education and practice guidelines are also important.”

Clinicians should also:

• Observe antibiotic best practices
• Optimize antibiotic selection and dosing
• Practice effective diagnostic stewardship
• Use the shortest duration of therapy necessary
• Avoid antibiotics for inappropriate indications
• Educate patients on when antibiotics are needed
• Follow and become good antibiotic stewardship mentors

“Multiple antibiotic stewardship interventions are effective, particularly those focused on behavioral interventions,” Dr. Cutrell said. “Every provider should follow antibiotic ‘best practices’ and other simple steps to prescribe antibiotics more wisely and to improve patient care.”

Dr. Cutrell reported financial relationships with Gilead Sciences and Regeneron Pharmaceuticals.

A version of this article first appeared on Medscape.com.

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.