Antimicrobial-resistant infections

An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.

The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country. 

Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.

They focused on the use of broad-spectrum antibiotics during the first 3 days of hospital admission, before microbiologic test results came back, and when clinicians are likely to err on the side of caution and prescribe one of the drugs, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine. 

“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said. 

Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said. 

“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said. 

The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection). 

Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic. 

But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%. 

An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level. 

Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization. 

For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001). 

“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.

“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle. 

The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”

The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group. 

“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.” 

The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.

A version of this article appeared on Medscape.com.

An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.

The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country. 

Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.

They focused on the use of broad-spectrum antibiotics during the first 3 days of hospital admission, before microbiologic test results came back, and when clinicians are likely to err on the side of caution and prescribe one of the drugs, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine. 

“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said. 

Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said. 

“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said. 

The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection). 

Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic. 

But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%. 

An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level. 

Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization. 

For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001). 

“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.

“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle. 

The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”

The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group. 

“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.” 

The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.

A version of this article appeared on Medscape.com.

An algorithm-driven risk assessment embedded in an electronic health record (EHR) helped clinicians reduce inappropriate broad-spectrum antibiotic prescribing by 17.4% and 28.4% in patients with UTIs and pneumonia, respectively, according to two related studies published in JAMA.

The randomized control trials included more than 200,000 adult patients with non–life threatening pneumonia or urinary tract infections (UTIs) in 59 hospitals owned by HCA Healthcare across the country. 

Researchers analyzed baseline prescribing behaviors over an 18-month period starting in April 2017, and data from a 15-month period of implementation of the new antibiotic system starting in April 2019.

They focused on the use of broad-spectrum antibiotics during the first 3 days of hospital admission, before microbiologic test results came back, and when clinicians are likely to err on the side of caution and prescribe one of the drugs, according to lead author Shruti K. Gohil, MD, MPH, associate medical director of epidemiology and infection prevention, infectious diseases at the University of California Irvine School of Medicine. 

“When a patient comes in with pneumonia or a UTI, it’s precisely because we are concerned that our patients have a multidrug-resistant organism that we end up using broad-spectrum antibiotics,” she said. 

Despite growing awareness of the need to reduce unnecessary antibiotic use, clinicians have still been slow to adopt a more conservative approach to prescribing, Dr. Gohil said. 

“What physicians have been needing is something to hang their hat on, to be able to say, ‘Okay, well, this one’s a low-risk person,’ ” Dr. Gohil said. 

The trials compared the impact of routine antibiotic activities with a stewardship bundle, called INSPIRE (Intelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection). 

Both groups received educational materials, quarterly coaching calls, prospective evaluations for antibiotic use, and were required to select a reason for prescribing an antibiotic. 

But prescribers in the intervention group took part in monthly coaching calls and feedback reports. In addition, if a clinician ordered a broad-spectrum antibiotic to treat pneumonia or a UTI outside of the intensive care unit within 72 hours of admission, an EHR prompt would pop up. The pop-up suggested a standard-spectrum antibiotic instead if patient risk for developing a multidrug-resistant (MDRO) version of either condition was less than 10%. 

An algorithm used data from the EHR calculated risk, using factors like patient demographics and history and MDRO infection at the community and hospital level. 

Prescribing rates were based on the number of days a patient received a broad-spectrum antibiotic during the first 72 hours of hospitalization. 

For the UTI intervention group, rates dropped by 17.4% (rate ratio [RR], 0.83; 95% CI, 0.77-0.89; P < .001), and 28.4% reduction in the pneumonia group (RR, 0.72; 95% CI, 0.66-0.78; P < .001). 

“We cannot know which element — prompt, education, or feedback — worked, but the data suggests that the prompt was the main driver,” Dr. Gohil said.

“In antibiotic stewardship, we have learned not only that doctors want to do the right thing, but that we as stewards need to make it easy for them do the right thing,” said Paul Pottinger, MD, professor of medicine at the Division of Allergy and Infectious Diseases at the University of Washington Medical Center in Seattle. 

The prompt “is your easy button,” said Dr. Pottinger, who was not involved with either study. “The researchers made it simple, fast, and straightforward, so people don’t have to think about it too much.”

The studies showed similar safety outcomes for the control and intervention groups. Among patients with a UTI, those in the control group were transferred to the ICU after an average of 6.6 days compared to 7 days in the intervention group. Among patients with pneumonia, the average days to ICU transfer were 6.5 for the control group and 7.1 for the intervention group. 

“This study is a proof of concept that physicians want to do the right thing and are willing to trust this information,” Dr. Pottinger said. “And this also shows us that this tool can be refined and made even more precise over time.” 

The study was funded by the US Centers for Disease Control and Prevention and was led by the University of California Irvine, Harvard Pilgrim Healthcare Institute, and HCA Healthcare System. Various authors report funding and support from entities outside the submitted work. The full list can be found with the original articles.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a medical device named the Sepsis ImmunoScore, which is an artificial intelligence/machine learning software, to guide rapid diagnosis and prediction of sepsis. The authorization was granted through the FDA’s De Novo pathway.

Sepsis is a complex condition, so diagnosing it early is difficult and has been a decades-long challenge for the US healthcare system.

Using both biomarkers and clinical data with the assistance of AI, the Sepsis ImmunoScore helps assess the risk for the presence of or progression to sepsis within 24 hours of patient evaluation in the emergency department or hospital. By considering 22 diverse parameters, the AI-powered tool provides a comprehensive evaluation of the patient’s biological condition, resulting in a risk score and categorization into four distinct risk levels.

It’s important to note that this system is not an alert mechanism. These risk categories are correlated with the risk for patient deterioration, including length of hospital stay, in-hospital mortality, and the need for escalated care within 24 hours (such as intensive care unit admission, mechanical ventilation, or vasopressor use). The diagnostic software is integrated directly into hospital electronic medical records.

This is the first AI diagnostic tool for sepsis to receive marketing authorization from the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a medical device named the Sepsis ImmunoScore, which is an artificial intelligence/machine learning software, to guide rapid diagnosis and prediction of sepsis. The authorization was granted through the FDA’s De Novo pathway.

Sepsis is a complex condition, so diagnosing it early is difficult and has been a decades-long challenge for the US healthcare system.

Using both biomarkers and clinical data with the assistance of AI, the Sepsis ImmunoScore helps assess the risk for the presence of or progression to sepsis within 24 hours of patient evaluation in the emergency department or hospital. By considering 22 diverse parameters, the AI-powered tool provides a comprehensive evaluation of the patient’s biological condition, resulting in a risk score and categorization into four distinct risk levels.

It’s important to note that this system is not an alert mechanism. These risk categories are correlated with the risk for patient deterioration, including length of hospital stay, in-hospital mortality, and the need for escalated care within 24 hours (such as intensive care unit admission, mechanical ventilation, or vasopressor use). The diagnostic software is integrated directly into hospital electronic medical records.

This is the first AI diagnostic tool for sepsis to receive marketing authorization from the FDA.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved a medical device named the Sepsis ImmunoScore, which is an artificial intelligence/machine learning software, to guide rapid diagnosis and prediction of sepsis. The authorization was granted through the FDA’s De Novo pathway.

Sepsis is a complex condition, so diagnosing it early is difficult and has been a decades-long challenge for the US healthcare system.

Using both biomarkers and clinical data with the assistance of AI, the Sepsis ImmunoScore helps assess the risk for the presence of or progression to sepsis within 24 hours of patient evaluation in the emergency department or hospital. By considering 22 diverse parameters, the AI-powered tool provides a comprehensive evaluation of the patient’s biological condition, resulting in a risk score and categorization into four distinct risk levels.

It’s important to note that this system is not an alert mechanism. These risk categories are correlated with the risk for patient deterioration, including length of hospital stay, in-hospital mortality, and the need for escalated care within 24 hours (such as intensive care unit admission, mechanical ventilation, or vasopressor use). The diagnostic software is integrated directly into hospital electronic medical records.

This is the first AI diagnostic tool for sepsis to receive marketing authorization from the FDA.

A version of this article appeared on Medscape.com.

TOPLINE:

A natural sugar used to treat recurring urinary tract infections (rUTIs) did not reduce future episodes, outpatient visits, the use of antibiotics, or symptoms compared with a placebo, according to a new study.

METHODOLOGY:

• D-Mannose is recommended as a natural alternative to antibiotics and sold as a dietary supplement; research showing the efficacy of D-mannose in treating UTIs is mixed.
• The double-blind, randomized controlled trial followed 598 women older than 18 years (median age, 61.3; range 18.2-93.5 years) with a history of rUTIs over 6 months from nearly 100 primary care clinics in the United Kingdom.
• Patients took 2 g of D-mannose or placebo powder daily and recorded their symptoms using a daily diary or through responses to health surveys, weekly questionnaires, and phone calls.
• Researchers checked medical records for urine culture results, antibiotic prescriptions, hospitalizations, and outpatient visits for UTIs.

TAKEAWAY:

• Approximately 51% of participants who took D-mannose and 55.7% of those who took a placebo contacted a healthcare professional reporting a UTI (relative risk, 0.92; 95% CI, 0.80-1.05; P = .22).
• Women in both groups reported similar durations of “moderately bad” or “worse” symptoms, and the number of antibiotic courses, instances of clinically suspected UTIs, and hospital admissions were similar between the two groups.
• Some studies have reported that synthetic mannosides are promising alternatives to D-mannose.

IN PRACTICE:

“D-Mannose should not be recommended to prevent future episodes of medically attended UTI in women with recurrent UTI in primary care,” the study authors wrote.

SOURCE:

The study was led by Gail Hayward, DPhil, associate professor at the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England, and was published online in JAMA Internal Medicine.

LIMITATIONS:

Some participants may have taken less than 2 mg/d or skipped days. Because researchers used powder rather than capsules, dosing could have been inconsistent. Researchers did not obtain a microbiologic confirmation for each rUTI. A small percentage of women were taking antibiotics.

DISCLOSURES:

The study was funded by the National Institute for Health and Care Research (NIHR) School for Primary Care Research and the NIHR Oxford Biomedical Research Centre. Various authors reported receiving support from the NIHR Health Protection Research Unit on Healthcare-Associated Infections and Antimicrobial Resistance and were NIHR investigators.

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

TOPLINE:

A natural sugar used to treat recurring urinary tract infections (rUTIs) did not reduce future episodes, outpatient visits, the use of antibiotics, or symptoms compared with a placebo, according to a new study.

METHODOLOGY:

• D-Mannose is recommended as a natural alternative to antibiotics and sold as a dietary supplement; research showing the efficacy of D-mannose in treating UTIs is mixed.
• The double-blind, randomized controlled trial followed 598 women older than 18 years (median age, 61.3; range 18.2-93.5 years) with a history of rUTIs over 6 months from nearly 100 primary care clinics in the United Kingdom.
• Patients took 2 g of D-mannose or placebo powder daily and recorded their symptoms using a daily diary or through responses to health surveys, weekly questionnaires, and phone calls.
• Researchers checked medical records for urine culture results, antibiotic prescriptions, hospitalizations, and outpatient visits for UTIs.

TAKEAWAY:

• Approximately 51% of participants who took D-mannose and 55.7% of those who took a placebo contacted a healthcare professional reporting a UTI (relative risk, 0.92; 95% CI, 0.80-1.05; P = .22).
• Women in both groups reported similar durations of “moderately bad” or “worse” symptoms, and the number of antibiotic courses, instances of clinically suspected UTIs, and hospital admissions were similar between the two groups.
• Some studies have reported that synthetic mannosides are promising alternatives to D-mannose.

IN PRACTICE:

“D-Mannose should not be recommended to prevent future episodes of medically attended UTI in women with recurrent UTI in primary care,” the study authors wrote.

SOURCE:

The study was led by Gail Hayward, DPhil, associate professor at the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England, and was published online in JAMA Internal Medicine.

LIMITATIONS:

Some participants may have taken less than 2 mg/d or skipped days. Because researchers used powder rather than capsules, dosing could have been inconsistent. Researchers did not obtain a microbiologic confirmation for each rUTI. A small percentage of women were taking antibiotics.

DISCLOSURES:

The study was funded by the National Institute for Health and Care Research (NIHR) School for Primary Care Research and the NIHR Oxford Biomedical Research Centre. Various authors reported receiving support from the NIHR Health Protection Research Unit on Healthcare-Associated Infections and Antimicrobial Resistance and were NIHR investigators.

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

TOPLINE:

A natural sugar used to treat recurring urinary tract infections (rUTIs) did not reduce future episodes, outpatient visits, the use of antibiotics, or symptoms compared with a placebo, according to a new study.

METHODOLOGY:

• D-Mannose is recommended as a natural alternative to antibiotics and sold as a dietary supplement; research showing the efficacy of D-mannose in treating UTIs is mixed.
• The double-blind, randomized controlled trial followed 598 women older than 18 years (median age, 61.3; range 18.2-93.5 years) with a history of rUTIs over 6 months from nearly 100 primary care clinics in the United Kingdom.
• Patients took 2 g of D-mannose or placebo powder daily and recorded their symptoms using a daily diary or through responses to health surveys, weekly questionnaires, and phone calls.
• Researchers checked medical records for urine culture results, antibiotic prescriptions, hospitalizations, and outpatient visits for UTIs.

TAKEAWAY:

• Approximately 51% of participants who took D-mannose and 55.7% of those who took a placebo contacted a healthcare professional reporting a UTI (relative risk, 0.92; 95% CI, 0.80-1.05; P = .22).
• Women in both groups reported similar durations of “moderately bad” or “worse” symptoms, and the number of antibiotic courses, instances of clinically suspected UTIs, and hospital admissions were similar between the two groups.
• Some studies have reported that synthetic mannosides are promising alternatives to D-mannose.

IN PRACTICE:

“D-Mannose should not be recommended to prevent future episodes of medically attended UTI in women with recurrent UTI in primary care,” the study authors wrote.

SOURCE:

The study was led by Gail Hayward, DPhil, associate professor at the Nuffield Department of Primary Care Health Sciences at the University of Oxford in England, and was published online in JAMA Internal Medicine.

LIMITATIONS:

Some participants may have taken less than 2 mg/d or skipped days. Because researchers used powder rather than capsules, dosing could have been inconsistent. Researchers did not obtain a microbiologic confirmation for each rUTI. A small percentage of women were taking antibiotics.

DISCLOSURES:

The study was funded by the National Institute for Health and Care Research (NIHR) School for Primary Care Research and the NIHR Oxford Biomedical Research Centre. Various authors reported receiving support from the NIHR Health Protection Research Unit on Healthcare-Associated Infections and Antimicrobial Resistance and were NIHR investigators.

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

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Dr. Merenstein

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Northwestern Medicine

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Dr. Merenstein

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Northwestern Medicine

Antibiotics had no measurable effect on the severity or duration of coughs due to acute lower respiratory tract infection (LRTI, or acute bronchitis), a large prospective study found.

In fact, those receiving an antibiotic in the primary- and urgent-care setting had a small but significant increase in overall length of illness (17.5 vs 15.9 days; P = .05) — largely because patients with longer illness before the index visit were more likely to receive these drugs. The study adds further support for reducing the prescription of antibiotics for LRTIs.

“Importantly, the pathogen data demonstrated that the length of time until illness resolution for those with bacterial infection was the same as for those not receiving an antibiotic versus those receiving one (17.3 vs 17.4 days),” researchers led by Daniel J. Merenstein, MD, a professor and director of research programs, family medicine, at Georgetown University Medical Center in Washington, wrote in the Journal of General Internal Medicine (doi: 10.1007/s11606-024-08758-y).

Dr. Merenstein

Risks

Overuse of antibiotics can result in dizziness, nausea, diarrhea, and rash, along with a roughly 4% chance of serious adverse effects including anaphylaxis; Stevens-Johnson syndrome, a serious skin and mucous membrane disorder; and Clostridioides difficile-associated diarrhea.

An estimated half of all antibiotic prescriptions for acute respiratory conditions are unnecessary. Before the COVID-19 pandemic, antibiotics were prescribed about 70% of the time for a diagnosis of uncomplicated cough and LRTI. The viral pandemic did not change this practice according to a meta-analysis of 130 studies showing that 78% of COVID-19 patients were prescribed an antibiotic.
 

The study

The study looked at a cohort of 718 patients, with a mean age of 38.9 years, 65.3% female, of whom 207 received an antibiotic and 511 did not. Of those with baseline data, 29% had an antibiotic prescribed at baseline, the most common (in 85%) being amoxicillin-clavulanate, azithromycin, doxycycline, and amoxicillin. Antibiotics had no effect on the duration or overall severity of cough in viral, bacterial, or mixed infections. Receipt of an antibiotic did, however, reduce the likelihood of a follow-up visit: 14.1% vs 8.2% (adjusted odds ratio, 0.47; 95% confidence interval, 0.26-0.84) — perhaps because it removed the motivation for seeking another consultation. Antibiotic recipients were more likely to receive a systemic corticosteroid (31.9% vs 4.5%, P <.001) and were also more likely to receive an albuterol inhaler (22.7% vs 7.6%, P <.001).

Jeffrey A. Linder, MD, MPH, a primary care physician and chief of internal medicine and geriatrics at Northwestern University Feinberg School of Medicine in Chicago, agrees that in the vast majority of LRTIs — usually acute bronchitis — antibiotics do not speed the healing process. “Forty years of research show that antibiotics do not make acute bronchitis go away any faster,” Dr. Linder, who was not involved in the current study, said in an interview. “There’s even growing evidence that a lot of pneumonia is viral as well, and 10 or 20 years from now we may often not be giving antibiotics for pneumonia because we’ll be able to see better if it’s caused by a virus.”

Northwestern Medicine

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

A decline in antibiotic-resistant bacteria has been observed in European countries that have curbed the use of antibiotics in both animals and humans, revealed the fourth joint interagency antimicrobial consumption and resistance analysis report.

The report was published by the European Centre for Disease Prevention and Control, the European Food Safety Authority, and the European Medicines Agency. Its findings were derived from an integrated analysis of the potential relationship between antimicrobial consumption (AMC) by humans and animals and the occurrence of antimicrobial resistance (AMR) using data collected between 2019 and 2021.
 

A Real Threat

AMR poses a significant threat to public and animal health, causing more than 35,000 deaths annually in the European Union (EU) and the European Economic Area. It also imposes a substantial economic burden on European healthcare systems, amounting to approximately €11.7 billion per year.

To address this challenge, the Council of the European Union recommended concerted and sustained efforts to achieve a 20% reduction in AMC in humans (compared with 2019 levels) and a 50% reduction in food-producing animals (compared with 2018 levels) by 2030. These targets are outlined in the European Commission’s Farm to Fork strategy.
 

It Really Works

Analysis of the trends of AMC and AMR in Escherichia coli from humans and food-producing animals, conducted for the first time, revealed that the susceptibility of E coli to antimicrobials in humans and animals increases with an overall decrease in the consumption of antibiotics.

Concurrent trends in AMC and AMR from 2014 to 2021 were also assessed. AMC in both human and animal sectors, measured in mg/kg of estimated biomass, was compared at country and European levels. In 2021, human AMC totaled 125.0 mg/kg of biomass, while food-producing animals registered 92.6 mg/kg of biomass.

Over the 2014-2021 period, total AMC in food-producing animals decreased by 44%, while in humans, it remained relatively stable. The consumption of certain antimicrobials was positively associated with resistance to those substances in bacteria from both humans and food-producing animals.

The report also highlighted that E coli resistance is linked in humans to the use of carbapenems, third- and fourth-generation cephalosporins, and quinolones and in food-producing animals to the administration of quinolones, polymyxins, aminopenicillins, and tetracyclines. Further, a connection exists between bacterial resistance in humans and food-producing animals, particularly for bacterial species such as Campylobacter jejuni and C coli.

The findings suggest that measures to reduce AMC in both food-producing animals and humans have been effective in many countries. However, reinforcing these measures is crucial to maintain and further advance reductions in AMC.
 

More Work

Aligned with the European Commission’s One Health holistic and coordinated approach to managing the human and veterinary sectors together, the European agencies advocate for:

• Sustained efforts to combat AMR at national, EU, and global levels.
• Coordinated surveillance of antibiotic use and AMR in both human and animal sectors.
• Continued research in the field of AMR.

The statistical code used to conduct these analyses was made publicly available in order to support further research analyses.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

TOPLINE:

Cefepime-taniborbactam was 22% more effective than meropenem, which is a current treatment for complicated urinary tract infections (UTIs) and acute pyelonephritis, according to a study published in The New England Journal of Medicine.

METHODOLOGY:

• Cefepime-taniborbactam is an antibiotic currently being explored as a treatment for antibiotic-resistant bacteria.
• The phase 3, double-blind, randomized trial included participants from 15 countries, including a safety group of 657 patients who were studied for adverse events and 436 in the micro intention-to-treat group who were studied for drug effectiveness.
• Each drug’s efficacy was measured as a combination of reduced bacteria levels and a resolution of symptoms and signs of infection.
• Patients in the study were over age 18; had a diagnosis of either complicated UTI or acute pyelonephritis; and had pyuria, at least one systemic sign, and at least one local sign or symptom. People were excluded if they had already received antibacterial drug therapy for more than 24 hours before randomization or had an infection with a meropenem-resistant pathogen.

TAKEAWAY:

• At days 19-23, 70.6% of patients in the cefepime-taniborbactam group showed a successful reduction in bacteria and symptoms compared with 58.0% in the meropenem group.
• Cefepime-taniborbactam was more effective than meropenem during follow-up, with 89.1% efficacy less than 24 hours after the last dose, compared to meropenem’s 86%. Cefepime-taniborbactam continued to have 63.8% efficacy up to 35 days after starting treatment, while meropenem was 51.7% during that timeframe.
• In the cefepime-taniborbactam group, 35.5% of patients experienced adverse effects that were mild to moderate, including headache, diarrhea, constipation, hypertension, and nausea, compared to 29% in the meropenem group.
• Overall, 3% of participants discontinued cefepime-taniborbactam and 1.8% discontinued meropenem, but reasons were heterogeneous.

IN PRACTICE:

“Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem,” the study authors wrote.

SOURCE:

Paul McGovern, MD, infectious disease specialist and senior vice president of Venatorx Pharmaceuticals, was the corresponding author of the study.

LIMITATIONS:

The authors reported no limitations.

DISCLOSURES:

The study was funded by Venatorx Pharmaceuticals, which received funding from the US Department of Health and Human Services, the Administration for Strategic Preparedness and Response, the Biomedical Advanced Research and Development Authority, the Global Antibiotic Research and Development Partnership, and Everest Medicines.

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

Hospital-acquired adverse events or conditions including falls and infections increased by approximately 25% after hospitals’ acquisition by private equity compared with control hospitals, on the basis of a study of Medicare claims for more than 4,500,000 hospitalizations.

“Prior research on private equity in health care showed that acquisition is associated with higher charges, prices, and spending; however, the implications for quality of care and patient outcomes remained less understood,” corresponding author Zirui Song, MD, of Harvard Medical School, Boston, said in an interview. “This was particularly true for measures of clinical quality that were less susceptible to changes in patient mix or coding behavior, such as hospital-acquired adverse events.”

In the study, published in JAMA, the researchers compared data from 100% Medicare Part A claims for 662,095 hospitalizations at 51 hospitals acquired by private equities and 4,160,720 hospitalizations at 259 control hospitals. The hospitalizations occurred between 2009 and 2019. The researchers also used a difference-in-differences design to evaluate hospitalizations from 3 years before to 3 years after acquisition, controlling for patient and hospital attributes.

Hospital-acquired adverse events as defined by the US Centers for Medicare & Medicaid Services included falls, infections, stage III or IV pressure ulcers, foreign objects retained after surgery, air embolism, and blood incompatibility.

Overall, Medicare patients in private equity hospitals experienced a 25.4% increase in hospital-acquired conditions compared with those in control hospitals through a period of up to 3 years after acquisition, with a difference of 4.6 additional hospital-acquired conditions per 10,000 hospitalizations (P = .004). Central line-associated bloodstream infections accounted for 37.7% of the increase (P = .04), despite a 16.2% decrease in placement of central lines, and falls accounted for 27.3% (P = .02).

Notably, the incidence of surgical site infections increased from 10.8 per 10,000 hospitalizations before acquisition to 21.6 per 10,000 hospitalizations after acquisition, despite a reduction of 8.1% in surgical volume. By contrast, surgical site infections decreased at control hospitals over the study period.

In-hospital mortality decreased slightly at private equity hospitals compared with the control hospitals, but there was no differential change in mortality by 30 days after hospital discharge. The slight difference might be caused by the trend in slightly younger Medicare beneficiaries treated at private equity hospitals; these patients were less likely to be eligible for both Medicaid and Medicare and were more likely to be transferred to other hospitals, the researchers noted.

The findings were limited by several factors including the lack of generalizability to all private equity-acquired hospitals and to non-Medicare patients, the researchers noted. Other limitations include the use of the International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes that might have failed to capture all hospital-acquired conditions and the inability to account for all confounding factors.

However, the results suggest that private equity acquisition was associated with increased hospital-acquired adverse events and highlight concerns about the impact of private equity ownership on healthcare delivery, the researchers concluded.

In a related story published in July 2023, this news organization described a report showing an association between private equity ownership of medical practices and increased consumer prices for multiple medical specialties.

“Medicare patients admitted to private equity-owned hospitals experienced, on average, an 25% increase in hospital-acquired adverse events after the hospital was bought compared to similar patients at hospitals not acquired by private equity firms. We were surprised by the extent of this change relative to the comparison (non-private equity) hospitals, including the sizable increase in central line-associated bloodstream infections and the doubling of surgical site infections at private equity hospitals — both of which went down at the comparison hospitals during the same period,” Dr. Song said in an interview.

“A key implication is that patients, providers, and policymakers might be more attuned to the potential clinical impact of private equity ownership in the delivery system. Given that a plausible explanation for these findings is reductions in clinician staffing, clinical organizations and policymakers might also be more aware of cost-cutting strategies after acquisition,” Dr. Song said. “Prior research has shown that hospitals, nursing homes, and physician practices experience staffing cuts after private equity acquisition, which is a common way to reduce operating costs and boost the profitability of acquired entities,” he noted.

“More research is needed to understand the impact of private equity acquisitions across health care settings and the potential effects of policy levers that aim to protect patients and societal resources,” said Dr. Song, who coauthored an article outlining a policy framework for addressing private equity in healthcare, published in JAMA in April 2023. “Potential regulatory remedies include minimum staffing ratios, antitrust enforcement, mitigating the financial risk of such acquisitions, increasing the transparency of these acquisitions, and protecting patients and society from the higher prices of care attributed to this model of provider ownership,” he said.
 

Patients Pay the Price of Private Equity Acquisition

“The exponential growth in private equity ownership in hospital and physician practices in the past few decades has left a majority of health care providers disillusioned with cost-cutting practices resulting in staffing reductions and ratios that sacrifice patient care as part of their approach to running clinical operations ‘lean,’ ” Robert Glatter, MD, an emergency medicine physician at Lenox Hill Hospital, New York, NY, said in an interview.

“While private equity companies argue that such practices are essential to meet their bottom line and increase operating margins, it doesn’t translate into ideal care for patients; lean practices in staffing which focus on profits at the expense of patient safety and quality of care.

“When you look at patient outcomes, it is the patients who ultimately pay the price — not the shareholders,” Dr. Glatter said. “This translates to higher risks of hospital-acquired complications including falls and blood-borne infections, including surgical site infections, as noted by the authors of the current study when private equity took over operations in hospitals.

Dr. Glatter said he was not surprised by the findings. “In my world, patient care and safety come first. Period,” he said. “Would you want your family’s health and well-being sacrificed in the name of company profits? I think it’s a rhetorical question, but one that every health care provider who works in a hospital or practice run by private equity must consider.”

Despite a decline in utilization at private equity hospitals as noted in the current study, hospital-acquired infections and adverse outcomes still increased, illustrating a decline in quality of care, said Dr. Glatter. “While these disparities were not evident when looking at 30-day outcomes, they demonstrate how operational changes impact patient outcomes in the near term. Having younger and healthier patients, and fewer Medicare and Medicaid patients combined with more hospital transfers to non–private equity run hospitals, resulted in lower in-hospital mortality in the near term, which was not apparent at 30 days post discharge,” he said.

“The explosion of hospital mergers and consolidation in the past several decades has led to skyrocketing health care costs at the expense of patient satisfaction, but also health care providers’ autonomy to manage and maintain quality care for their patients,” Dr. Glatter said.

“It’s important to understand that private equity’s interests are primarily aligned with their shareholder’s interests, as opposed to patients’ outcomes and interests,” Dr. Glatter told this news organization. “Within 5-7 years, the goal is to increase operating margins and profits and then sell a practice or hospital, which is ultimately part of a ‘health care portfolio,’ ” he said.

Additional research is needed to examine whether other hospital-acquired conditions including pressure sores, catheter-associated UTIs, methicillin-resistant Staphylococcus aureus infections, Clostridium difficile infections, and nosocomial pneumonia have increased in hospitals following private equity acquisition, given the overall national decline in these events, he said.

“At the same time, it is vital to also look at management and readmission rates for patients with strokes, heart attacks, and congestive heart failure in hospitals that are run by private equity,” Dr. Glatter noted. “These are important benchmarks of care monitored by CMS that reflect the quality of care that payers ultimately factor into reimbursement.”

Examining the metrics associated with these diagnoses will help in understanding whether private equity-managed facilities are leading to adverse outcomes and mortality, increased length of stay, hospital readmissions, and increased nosocomial infections, apart from other aspects of patient experience, Dr. Glatter added.

The study was supported by the National Heart, Lung, and Blood Institute, the National Institute on Aging, and Arnold Ventures. The researchers had no financial conflicts to disclose. Dr. Glatter had no financial conflicts to disclose and serves on the Medscape Emergency Medicine Editorial Board.
 

A version of this article appeared on Medscape.com.

Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.

This drug, isolated from bacteria that haven’t previously been studied, seems to be capable of combating multidrug-resistant “superbugs” thanks to unusual mechanisms of action.

The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.

Their research was published in Cell.

“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
 

Microbial “dark matter”

Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.

This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
 

Combats resistant bacteria

In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.

Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
 

Original mechanism of action

Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.

“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.

The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.

Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
 

Few side effects

Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.

“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.

Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.

In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
 

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.

This drug, isolated from bacteria that haven’t previously been studied, seems to be capable of combating multidrug-resistant “superbugs” thanks to unusual mechanisms of action.

The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.

Their research was published in Cell.

“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
 

Microbial “dark matter”

Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.

This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
 

Combats resistant bacteria

In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.

Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
 

Original mechanism of action

Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.

“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.

The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.

Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
 

Few side effects

Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.

“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.

Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.

In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
 

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Antibiotic resistance is a major public health problem. Few new molecules are in development, but a new antibiotic called clovibactin brings hope.

This drug, isolated from bacteria that haven’t previously been studied, seems to be capable of combating multidrug-resistant “superbugs” thanks to unusual mechanisms of action.

The drug was discovered and has been studied by scientists from Utrecht University in the Netherlands, the University of Bonn in Germany, the German Center for Infection Research, Northeastern University in Boston, and NovoBiotic Pharmaceuticals in Cambridge, Mass.

Their research was published in Cell.

“Since clovibactin was isolated from bacteria that could not be grown before, pathogenic bacteria have not seen such an antibiotic before and had no time to develop resistance,” Markus Weingarth, MD, PhD, a researcher in Utrecht University’s chemistry department, said in a press release.
 

Microbial “dark matter”

Researchers isolated clovibactin from sandy soil from North Carolina and studied it using the iChip device, which was developed in 2015. This technique allowed them to grow “bacterial dark matter,” so-called unculturable bacteria, which compose a group to which 99% of bacteria belong.

This device also paved the way for the discovery of the antibiotic teixobactin in 2020. Teixobactin is effective against gram-positive bacteria and is one of the first truly new antibiotics in decades. Its mechanism of action is like that of clovibactin.
 

Combats resistant bacteria

In the Cell article, the researchers showed that clovibactin acts via several mechanisms and that it successfully treated mice infected with the superbug Staphylococcus aureus.

Clovibactin exhibited antibacterial activity against a broad range of gram-positive pathogens, including methicillin-resistant S. aureus, daptomycin-resistant and vancomycin-resistant S. aureus strains, and difficult-to-treat vancomycin-resistant Enterococcus faecalis and E faecium (vancomycin-resistant enterococci). Escherichia coli was only marginally affected “compared with an outer membrane deficient E. coli WO153 strain, probably reflecting insufficient penetration of the compound,” the authors wrote.
 

Original mechanism of action

Clovibactin acts not on one but three molecules, all of which are essential to the construction of bacterial walls: C55PP, lipid II, and lipid IIIWTA, which are from different cell wall biosynthetic pathways. Clovibactin binds to the pyrophosphate portion of these precursors.

“Clovibactin wraps around the pyrophosphate like [a] tight glove, like a cage that encloses its target,” said Dr. Weingarth. This is what gives clovibactin its name, which is derived from Greek word klouvi, meaning cage.

The remarkable aspect of clovibactin’s mechanism is that it only binds to the immutable pyrophosphate that is common to cell wall precursors, but it also ignores the variable sugar-peptide part of the targets. The bacteria therefore have a much harder time developing resistance against it. “In fact, we did not observe any resistance to clovibactin in our studies,” Dr. Weingarth confirmed.

Upon binding the target molecules, it self-assembles into large fibrils on the surface of bacterial membranes. These fibrils are stable for a long time and thereby ensure that the target molecules remain sequestered for as long as necessary to kill bacteria.
 

Few side effects

Because of the mechanism of action of the antibiotic, few side effects are predicted. Indeed, clovibactin targets bacteria cells but not human cells.

“Since these fibrils only form on bacterial membranes and not on human membranes, they are presumably also the reason why clovibactin selectively damages bacterial cells but is not toxic to human cells,” said Dr. Weingarth.

Other studies – in particular, studies in humans – are needed before the antibiotic can be considered a potential treatment. In the meantime, regulations regarding the proper use of antibiotics must continue to be applied to limit antibiotic resistance.

In 2019, 4.95 million deaths worldwide were associated with bacterial antimicrobial resistance, including 1.27 million deaths directly attributable to bacterial antimicrobial resistance. If this trend continues without new medicines becoming available to treat bacterial infections, it is estimated that by 2050, 10 million people will die every year from antimicrobial drug resistance.
 

This article was translated from the Medscape French Edition. A version appeared on Medscape.com.

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Variability in antimicrobial prescribing among hospital-based physicians is not associated with patient characteristics or clinical outcomes, data suggest. The lowest level of such prescribing within each hospital could be considered a target for antimicrobial stewardship, according to the researchers.

In a multicenter study of 124 physicians responsible for more than 124,000 hospitalized patients, the difference in mean prescribing between the highest and lowest quartiles of prescription volume was 15.8 days of treatment per 100 patient-days.

Baseline patient characteristics were similar across the quartiles, and there were no differences in patient outcomes, including in-hospital deaths, hospital length of stay, intensive care unit transfer, and hospital readmission.

Although the investigators expected variation in prescribing, “what surprised us most was the limited association with any differences in clinical outcomes, particularly when it came to the amount of antimicrobials used,” study author Mark T. McIntyre, PharmD, pharmacotherapy specialist at the Sinai Health System in Toronto, told this news organization.

“Importantly, this is not a study that defines quality of care,” he said. “We looked at natural variation in practice and association with outcomes. So, I don’t want clinicians to think, ‘Well, I’m high, therefore I’m bad,’ or, ‘I’m low, therefore I’m good.’

“This is an early explanatory analysis that asks whether this is an opportunity to optimize prescribing in ways we hadn’t thought of before,” he said. “Now that we don’t have an association with higher or lower prescribing and outcomes, we can look at what else is driving that antimicrobial prescribing and what we can do about it. Comfort level, risk tolerance, and social, cultural, and contextual factors all likely play a role.”

The study was published online in the Canadian Medical Association Journal.
 

Antimicrobial reductions possible

The investigators conducted a retrospective cohort study using the General Medicine Inpatient Initiative database to assess physician-level volume and spectrum of antimicrobial prescribing in adult general medical wards. Four academic hospitals in Toronto were evaluated for the period 2010 to 2019.

The investigators stratified physicians into quartiles by hospital site on the basis of volume of antimicrobial prescribing (specifically, days of therapy per 100 patient-days and antimicrobial-free days) and antibacterial spectrum (modified spectrum score, which assigns a value to each antibacterial agent on the basis of its breadth of coverage).

They also examined potential differences between physician quartiles in patient characteristics, such as age, sex, the Laboratory-Based Acute Physiology Score, discharge diagnosis, and the Charlson Comorbidity Index.

Multilevel modeling allowed the investigators to evaluate the association between clinical outcomes and antimicrobial volume and spectrum.

The primary measure was days of therapy per 100 patient-days.

As noted, the cohort included 124 physicians who were responsible for 124,158 hospital admissions. The median physician-level volume of antimicrobial prescribing was 56.1 days of therapy per 100 patient-days. Patient characteristics were balanced across the quartiles of physician prescribing.

The difference in mean prescribing between physician quartile 4 and quartile 1 was 15.8 days of therapy per 100 patient-days, meaning the median physician in quartile 4 prescribed antimicrobials at a volume that was 30% higher than that of the median physician in quartile 1.

No significant differences were noted for any clinical outcome with regard to quartile of days of therapy, antimicrobial-free days, or modified spectrum score after adjustment for patient-level characteristics.

In addition, no significant differences in the case mix between quartile 4 and quartile 1 were found when the cohort was restricted to patients admitted and discharged by the same most responsible person, nor were differences found in an analysis that was restricted to those without a discharge diagnosis code of palliative care.

In-hospital mortality was higher among patients cared for by prescribers with higher modified spectrum scores (odds ratio, 1.13). “We still can’t fully explain this finding,” Dr. McIntyre acknowledged. “We only saw that in our primary analysis. When we did several sensitivity analyses, that finding didn’t appear.”

The authors concluded, “Ultimately, without discernible benefit in outcomes of patients of physicians who prescribe more frequently, less antimicrobial exposure may be possible, leading to lower risk of antimicrobial resistance.”
 

Decision-making support

Commenting on the study, Lawrence I. Kaplan, MD, section chief of general internal medicine and associate dean for interprofessional education at the Lewis Katz School of Medicine at Temple University in Philadelphia, said, “Trying to get to the lowest quartile would be a goal, and given that physician characteristics are involved, I think there needs to be much better training in clinical management decision-making: how you come about making a decision based on a diagnosis for a particular patient, in or out of the hospital.” Dr. Kaplan was not involved in the research.

“Clinical decision-making tools that can be plugged into the electronic health record can help,” he suggested. “The tools basically ask if a patient meets certain criteria and then might give a prompt that says, for example, ‘These symptoms are not consistent with bacterial sinusitis. The patient should be treated with decongestants, nasal steroids, et cetera, because antibiotics aren’t appropriate.’

“It’s a bit like checkbox medicine, which a lot of physicians bridle at,” he said. “But if it’s really based on evidence, I think that’s an appropriate use of evidence-based medicine.”

Dr. Kaplan said that more research is needed into the best way to get a physician or any provider to step back and say, “Is this the right decision?” or, “I’m doing this but I’m really on shaky ground. What am I missing?’” He noted that the Society for Medical Decision Making publishes research and resources in this area.

“I love the fact that the paper was authored by an interdisciplinary group,” Dr. Kaplan added. “A pharmacist embedded in the team can, for example, help with treatment decision-making and point out potential drug interactions that prescribers might not be aware of.

“We need to stop practicing medicine siloed, which is what we do a lot of ways, both in the hospital and out of the hospital, because it’s the path of least resistance,” Dr. Kaplan added. “But when we can say, ‘Hey, I have a question about this,’ be it to a computer or a colleague, I would argue that we come up with better care.”

No funding was provided for the study. Dr. McIntyre and Dr. Kaplan have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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

This transcript has been edited for clarity.

Clostridioides difficile is a toxin-based infection that takes up residence in the colon due to disturbed normal bowel flora, usually after antibiotics.

Recurrent C. difficile can happen in up to a quarter of patients who receive oral vancomycin as a treatment for their infection. It can also occur with treatment with the newer agent, fidaxomicin, although possibly in fewer patients. In general, relapses are indeed common.

When I trained at Johns Hopkins under John Bartlett, he took the approach that after the second – and always after the third – relapse, an extended course of oral therapy with vancomycin could help get patients out of trouble. He used the so-called extended pulse method, where patients would take the drug for approximately 4-6 weeks and gradually reduce the dose.

This approach can also be done with fidaxomicin. However, I’m not sure it works much better than vancomycin, and there are often hurdles to using fidaxomicin because of insurers not approving it because of the expense.

What other therapies are there?

There is bezlotoxumab, which is a human monoclonal antibody targeting C. difficile toxin B. I’ve used it a few times. It is given as a one-time infusion, and there are challenges regarding cost, the logistics of setting up the infusion, and insurance approval.
 

Fecal microbiota transplant

In recent years, fecal microbiota transplants (FMT) have received a lot of attention as a different avenue of treatment that could lower the potential for relapses, with success rates usually around 80%-90%. However, in the past few years, there have been some serious safety signals because of possible transmission of dangerous pathogens, often with drug resistance, with FMT.

I’m therefore pleased to say that newer fecal microbiota products are coming in fast and furious. I thought I’d spend a few minutes speaking about these.

OpenBiome, an organization dedicated to microbiome research, offers an investigational product from screened donors that has not received Food and Drug Administration approval. It’s been around for some time. It can be used in either upper or lower GI applications, and the organization cites about an 84% success rate using this product.

There are also two new FDA-approved products I think are worth knowing about. They’ve just been approved recently and we’re a little uncertain of where they’re going to end up in the treatment landscape.

The first is from Ferring, and it goes by fecal microbiota, live-jslm (Rebyota). This is a product from qualified and screened donors, the main component of which is Bacteroides, which is given as a single dose by enema.

The company did a phase 3 trial with a Bayesian primary analysis, which I think convinced the FDA to approve this product. The success rate in people with multiple relapses was 70.6%, compared with 57.5% with placebo. The estimated treatment effect was 13.1%. Of those who did respond, over 90% were kept free of relapse over a 6-month period.

The other product, also FDA approved, is from Seres. It was previously called SER-109, and is now called fecal microbiota spores, live-brpk (Vowst). Unlike the previous product, this is orally administered, with patients taking four capsules daily for 3 days. Again, these donor-derived firmicutes have been appropriately screened and are free of potential pathogens.

The phase 3 randomized clinical trial results were published in the New England Journal of Medicine. They showed that 12% of those taking this product had a relapse, compared with 40% of those taking placebo, which is about the range we tend to see in people who have had multiple relapses. The safety profile was similar to placebo.

So, how will people use these treatments?

I think the FDA imprimatur will be attractive to people, but the products, I believe, will be priced fairly expensively, in the under $10,000 range. The first (Rebyota) is a rectal infusion; it is a one-and-done treatment but creates logistical issues. Interestingly, it could be a billable procedure for infectious disease clinicians. The ease of oral administration for Vowst, no doubt, will be very appealing. Both of these are given after completing a course of treatment with vancomycin or fidaxomicin so as not to interfere with the microbiome product.

I’ll also briefly mention a paper published in JAMA on yet another microbiome product, called VE303. This product was based on eight commensal strains of Clostridia and was given orally in a phase 2 trial. Interestingly, this worked about the same as the oral product that is already FDA approved. The study showed a recurrence rate of 13.8% in the high-dose group, compared with 45.5% in the placebo group.

I think this is exciting. Hopefully, we will have safer products that can be more reliable, although there are some concerns and logistical challenges in safely getting the products to people. And, of course, there is the expense.

But anything that can be done to help improve these patients is welcome, as once they get into the multiple-relapse phase, it is challenging to turn around. These commercialized products will hopefully become a bit more mainstream. Certainly, we’ll see how these will be utilized in the coming months and over the next few years.

Dr. Auwaerter is Clinical Director, Division of Infectious Diseases, Johns Hopkins University, Baltimore. He reported conflicts of interest with Gilead, Shionogi, and Medscape.

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