Antimicrobial-resistant infections

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A ‘huge infectious burden’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A ‘huge infectious burden’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A ‘huge infectious burden’

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Rampant misuse

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

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

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

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

How to be a better steward

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

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

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

Clinicians should also:

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

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

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

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

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

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

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

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

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

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

Rampant misuse

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

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

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

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

How to be a better steward

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

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

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

Clinicians should also:

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

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

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

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

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

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

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

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

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

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

Rampant misuse

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

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

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

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

How to be a better steward

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

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

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

Clinicians should also:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

High-, middle-, and low-income countries

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

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

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

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

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

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

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

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

NeoSep-1 trial to compare multiple different treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

High-, middle-, and low-income countries

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

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

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

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

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

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

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

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

NeoSep-1 trial to compare multiple different treatments

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

High-, middle-, and low-income countries

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

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

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

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

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

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

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

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

NeoSep-1 trial to compare multiple different treatments

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

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

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

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

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

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

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

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

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

LISBON – Screening for Staphylococcus aureus, decolonization, and use of teicoplanin for surgical antimicrobial prophylaxis among patients with methicillin-resistant S. aureus (MRSA) lowered the number of prosthetic joint infections in elderly patients undergoing surgery for fracture of the femur.

The findings were presented in a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, which was one of the few awarded the accolade of “top-rated poster.”

“We actually found that with our intervention, all prosthetic joint infections decreased, not just the Staphylococcus aureus but those due to MRSA, too,” Natividad Benito, MD, an infectious diseases specialist at Hospital de la Santa Creu i Sant Pau in Barcelona, said in an interview. “We’re pleased with these results because prosthetic joint infections present such a complicated situation for patients and surgeons. This is also a relatively easy intervention to use, and with time, even the PCR [polymerase chain reaction] technology will become cheaper. Now, in our hospital, prosthetic joint infections are rare.”

At Hospital de la Santa Creu i Sant Pau, around 200 hip hemiarthroplasties are performed per year. Preceding the intervention, the hospital recorded 11 prosthetic joint infections, with up to five infections due to S. aureus and up to four due to MRSA.

The intervention was introduced in 2016. After 2 years, there were no cases of prosthetic joint infections due to S. aureus; in 2018 there, was one case of prosthetic joint infection due to MRSA. In 2019, there was one case of prosthetic joint infection, but it was due neither to S. aureus nor MRSA. In 2020 and 2021, there was one infection each year that was due to MRSA.

Jesús Rodríguez Baño, MD, head of the infectious diseases division, Hospital Universitario Virgen Macarena at the University of Seville, Spain, who was not involved in the study, explained that for patients with hip fracture, “the time frame in which colonization can be studied is too short using traditional methods. Prosthetic joint infections in this population have a devastating effect, with not negligible mortality and very important morbidity and health care costs.”

Referring to the significant reduction in the rate of S. aureus prosthetic joint infections in the postintervention period, Dr. Rodríguez Baño said in an interview, “The results are sound, and the important reduction in infection risk invites for the development of a multicenter, randomized trial to confirm these interesting results.

“The authors are commended for measuring the impact of applying a well-justified preventive protocol,” Dr. Rodríguez Baño added. However, the study has some limitations: “It was performed in one center, it was not randomized, and control for potential confounders is needed.”
 

Decolonization in an emergency femur fracture

This study addressed a particular need in residents of Spain’s long-term care facilities. In 2016, the prevalence of MRSA was high.

Roughly one-third of the general population carry S. aureus in their noses. In care homes, the rate of MRSA is higher than in the general population, at around 30% of those with S. aureus. In Spain, recommendations for patients undergoing elective total joint arthroplasty advise S. aureus decolonization – which can take 5 days – to prevent surgical site infections.

“The problem with the elderly population is not only have they a higher incidence of MRSA but that the surgical prophylaxis is inadequate for MRSA,” Dr. Benito pointed out.

Many patients in long-term care facilities are elderly and frail and are at greater risk of fracture. Unlike elective hip surgery, in which patients are asked to undergo decolonization over the 5 days prior to their operation, with emergent femur fractures, there is insufficient time for such preparation. “These patients with femur fractures need surgery as soon as possible,” said Dr. Benito.

No studies have been conducted to determine the best way to minimize infection risk from S. aureus and MRSA for patients undergoing emergency hip hemiarthroplasty surgery to treat femoral fractures.

In the current study, Dr. Benito and coauthors assessed whether a bundle of measures – including rapid detection of S. aureus nasal carriage by PCR upon arrival in the emergency setting, followed by decolonization of carriers using a topical treatment in the nose and a prescription of surgical antimicrobial prophylaxis (adapted antibiotic prophylaxis for MRSA) – reduces the incidence of prosthetic joint infections after surgery.

The quasi-experimental single-center study included patients admitted to the emergency department at Hospital de la Santa Creu i Sant Pau. The PCR was rapid, with a turnaround of just 1.5 hours. Decolonization of S. aureus carriers was carried out using nasal mupirocin and chlorhexidine gluconate bathing, which was started immediately. It was used for a 5 days and was usually continued throughout and after surgery.

Patients carrying MRSA received teicoplanin as optimal surgical antimicrobial prophylaxis instead of cefazolin. The intervention did not interfere with the timing of surgery. The study’s principal outcomes were overall incidence of prosthetic joint infections and the incidence of those specifically caused by S. aureus and MRSA.

The researchers compared findings regarding these outcomes over 5 consecutive years of the intervention to outcomes during 4 consecutive years prior to the intervention, which started in 2016.

During 2016-2020, from 22% to 31% of the overall number of patients requiring hip hemiarthroplasty were referred from long-term care facilities. From 25% to 29% of these patients tested positive for S. aureus on PCR, and of these, 33%-64% had MRSA.

There were 772 surgical procedures from 2012 to 2015 and 786 from 2017 to 2020.

Prior to the intervention, over the years 2012-2014, S. aureus caused 36%-50% of prosthetic joint infections; 25%-100% of the S. aureus infections were MRSA. This decreased significantly after the intervention.

During 2016-2020, there was an average of 14 prosthetic joint infections (1.5%), compared to 36 (4.7%) in 2012-2015 (P < .001). Similarly, the incidence of prosthetic joint infections due to S. aureus dropped to 0.3% from 1.8% (P < .002). The incidence of MRSA prosthetic joint infections was 0.3% for 2016-2020, versus 1.2% for 2012-2015 (P = .012).

The years 2018, 2020, and 2021 each saw one case of infection due to MRSA. They were most likely due to “the intervention not being performed properly in all cases,” said Dr. Benito.

A prosthetic joint infection is very serious for the patient. “It means reoperating, because antibiotics are not enough to clear the infection. The biofilm and pus of the infection need to be cleaned out, a new prosthesis is needed, after which more antibiotics are needed for around 2 months, which can be hard to tolerate, and even then, the infection might not be eradicated,” explained Dr. Benito. “Many of these people are old and frail, and mortality can be significant. Getting a prosthetic joint infection is catastrophic for these patients.”

Dr. Benito and Dr. Rodríguez-Baño have disclosed no relevant financial relationships.

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

LISBON – Screening for Staphylococcus aureus, decolonization, and use of teicoplanin for surgical antimicrobial prophylaxis among patients with methicillin-resistant S. aureus (MRSA) lowered the number of prosthetic joint infections in elderly patients undergoing surgery for fracture of the femur.

The findings were presented in a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, which was one of the few awarded the accolade of “top-rated poster.”

“We actually found that with our intervention, all prosthetic joint infections decreased, not just the Staphylococcus aureus but those due to MRSA, too,” Natividad Benito, MD, an infectious diseases specialist at Hospital de la Santa Creu i Sant Pau in Barcelona, said in an interview. “We’re pleased with these results because prosthetic joint infections present such a complicated situation for patients and surgeons. This is also a relatively easy intervention to use, and with time, even the PCR [polymerase chain reaction] technology will become cheaper. Now, in our hospital, prosthetic joint infections are rare.”

At Hospital de la Santa Creu i Sant Pau, around 200 hip hemiarthroplasties are performed per year. Preceding the intervention, the hospital recorded 11 prosthetic joint infections, with up to five infections due to S. aureus and up to four due to MRSA.

The intervention was introduced in 2016. After 2 years, there were no cases of prosthetic joint infections due to S. aureus; in 2018 there, was one case of prosthetic joint infection due to MRSA. In 2019, there was one case of prosthetic joint infection, but it was due neither to S. aureus nor MRSA. In 2020 and 2021, there was one infection each year that was due to MRSA.

Jesús Rodríguez Baño, MD, head of the infectious diseases division, Hospital Universitario Virgen Macarena at the University of Seville, Spain, who was not involved in the study, explained that for patients with hip fracture, “the time frame in which colonization can be studied is too short using traditional methods. Prosthetic joint infections in this population have a devastating effect, with not negligible mortality and very important morbidity and health care costs.”

Referring to the significant reduction in the rate of S. aureus prosthetic joint infections in the postintervention period, Dr. Rodríguez Baño said in an interview, “The results are sound, and the important reduction in infection risk invites for the development of a multicenter, randomized trial to confirm these interesting results.

“The authors are commended for measuring the impact of applying a well-justified preventive protocol,” Dr. Rodríguez Baño added. However, the study has some limitations: “It was performed in one center, it was not randomized, and control for potential confounders is needed.”
 

Decolonization in an emergency femur fracture

This study addressed a particular need in residents of Spain’s long-term care facilities. In 2016, the prevalence of MRSA was high.

Roughly one-third of the general population carry S. aureus in their noses. In care homes, the rate of MRSA is higher than in the general population, at around 30% of those with S. aureus. In Spain, recommendations for patients undergoing elective total joint arthroplasty advise S. aureus decolonization – which can take 5 days – to prevent surgical site infections.

“The problem with the elderly population is not only have they a higher incidence of MRSA but that the surgical prophylaxis is inadequate for MRSA,” Dr. Benito pointed out.

Many patients in long-term care facilities are elderly and frail and are at greater risk of fracture. Unlike elective hip surgery, in which patients are asked to undergo decolonization over the 5 days prior to their operation, with emergent femur fractures, there is insufficient time for such preparation. “These patients with femur fractures need surgery as soon as possible,” said Dr. Benito.

No studies have been conducted to determine the best way to minimize infection risk from S. aureus and MRSA for patients undergoing emergency hip hemiarthroplasty surgery to treat femoral fractures.

In the current study, Dr. Benito and coauthors assessed whether a bundle of measures – including rapid detection of S. aureus nasal carriage by PCR upon arrival in the emergency setting, followed by decolonization of carriers using a topical treatment in the nose and a prescription of surgical antimicrobial prophylaxis (adapted antibiotic prophylaxis for MRSA) – reduces the incidence of prosthetic joint infections after surgery.

The quasi-experimental single-center study included patients admitted to the emergency department at Hospital de la Santa Creu i Sant Pau. The PCR was rapid, with a turnaround of just 1.5 hours. Decolonization of S. aureus carriers was carried out using nasal mupirocin and chlorhexidine gluconate bathing, which was started immediately. It was used for a 5 days and was usually continued throughout and after surgery.

Patients carrying MRSA received teicoplanin as optimal surgical antimicrobial prophylaxis instead of cefazolin. The intervention did not interfere with the timing of surgery. The study’s principal outcomes were overall incidence of prosthetic joint infections and the incidence of those specifically caused by S. aureus and MRSA.

The researchers compared findings regarding these outcomes over 5 consecutive years of the intervention to outcomes during 4 consecutive years prior to the intervention, which started in 2016.

During 2016-2020, from 22% to 31% of the overall number of patients requiring hip hemiarthroplasty were referred from long-term care facilities. From 25% to 29% of these patients tested positive for S. aureus on PCR, and of these, 33%-64% had MRSA.

There were 772 surgical procedures from 2012 to 2015 and 786 from 2017 to 2020.

Prior to the intervention, over the years 2012-2014, S. aureus caused 36%-50% of prosthetic joint infections; 25%-100% of the S. aureus infections were MRSA. This decreased significantly after the intervention.

During 2016-2020, there was an average of 14 prosthetic joint infections (1.5%), compared to 36 (4.7%) in 2012-2015 (P < .001). Similarly, the incidence of prosthetic joint infections due to S. aureus dropped to 0.3% from 1.8% (P < .002). The incidence of MRSA prosthetic joint infections was 0.3% for 2016-2020, versus 1.2% for 2012-2015 (P = .012).

The years 2018, 2020, and 2021 each saw one case of infection due to MRSA. They were most likely due to “the intervention not being performed properly in all cases,” said Dr. Benito.

A prosthetic joint infection is very serious for the patient. “It means reoperating, because antibiotics are not enough to clear the infection. The biofilm and pus of the infection need to be cleaned out, a new prosthesis is needed, after which more antibiotics are needed for around 2 months, which can be hard to tolerate, and even then, the infection might not be eradicated,” explained Dr. Benito. “Many of these people are old and frail, and mortality can be significant. Getting a prosthetic joint infection is catastrophic for these patients.”

Dr. Benito and Dr. Rodríguez-Baño have disclosed no relevant financial relationships.

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

LISBON – Screening for Staphylococcus aureus, decolonization, and use of teicoplanin for surgical antimicrobial prophylaxis among patients with methicillin-resistant S. aureus (MRSA) lowered the number of prosthetic joint infections in elderly patients undergoing surgery for fracture of the femur.

The findings were presented in a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, which was one of the few awarded the accolade of “top-rated poster.”

“We actually found that with our intervention, all prosthetic joint infections decreased, not just the Staphylococcus aureus but those due to MRSA, too,” Natividad Benito, MD, an infectious diseases specialist at Hospital de la Santa Creu i Sant Pau in Barcelona, said in an interview. “We’re pleased with these results because prosthetic joint infections present such a complicated situation for patients and surgeons. This is also a relatively easy intervention to use, and with time, even the PCR [polymerase chain reaction] technology will become cheaper. Now, in our hospital, prosthetic joint infections are rare.”

At Hospital de la Santa Creu i Sant Pau, around 200 hip hemiarthroplasties are performed per year. Preceding the intervention, the hospital recorded 11 prosthetic joint infections, with up to five infections due to S. aureus and up to four due to MRSA.

The intervention was introduced in 2016. After 2 years, there were no cases of prosthetic joint infections due to S. aureus; in 2018 there, was one case of prosthetic joint infection due to MRSA. In 2019, there was one case of prosthetic joint infection, but it was due neither to S. aureus nor MRSA. In 2020 and 2021, there was one infection each year that was due to MRSA.

Jesús Rodríguez Baño, MD, head of the infectious diseases division, Hospital Universitario Virgen Macarena at the University of Seville, Spain, who was not involved in the study, explained that for patients with hip fracture, “the time frame in which colonization can be studied is too short using traditional methods. Prosthetic joint infections in this population have a devastating effect, with not negligible mortality and very important morbidity and health care costs.”

Referring to the significant reduction in the rate of S. aureus prosthetic joint infections in the postintervention period, Dr. Rodríguez Baño said in an interview, “The results are sound, and the important reduction in infection risk invites for the development of a multicenter, randomized trial to confirm these interesting results.

“The authors are commended for measuring the impact of applying a well-justified preventive protocol,” Dr. Rodríguez Baño added. However, the study has some limitations: “It was performed in one center, it was not randomized, and control for potential confounders is needed.”
 

Decolonization in an emergency femur fracture

This study addressed a particular need in residents of Spain’s long-term care facilities. In 2016, the prevalence of MRSA was high.

Roughly one-third of the general population carry S. aureus in their noses. In care homes, the rate of MRSA is higher than in the general population, at around 30% of those with S. aureus. In Spain, recommendations for patients undergoing elective total joint arthroplasty advise S. aureus decolonization – which can take 5 days – to prevent surgical site infections.

“The problem with the elderly population is not only have they a higher incidence of MRSA but that the surgical prophylaxis is inadequate for MRSA,” Dr. Benito pointed out.

Many patients in long-term care facilities are elderly and frail and are at greater risk of fracture. Unlike elective hip surgery, in which patients are asked to undergo decolonization over the 5 days prior to their operation, with emergent femur fractures, there is insufficient time for such preparation. “These patients with femur fractures need surgery as soon as possible,” said Dr. Benito.

No studies have been conducted to determine the best way to minimize infection risk from S. aureus and MRSA for patients undergoing emergency hip hemiarthroplasty surgery to treat femoral fractures.

In the current study, Dr. Benito and coauthors assessed whether a bundle of measures – including rapid detection of S. aureus nasal carriage by PCR upon arrival in the emergency setting, followed by decolonization of carriers using a topical treatment in the nose and a prescription of surgical antimicrobial prophylaxis (adapted antibiotic prophylaxis for MRSA) – reduces the incidence of prosthetic joint infections after surgery.

The quasi-experimental single-center study included patients admitted to the emergency department at Hospital de la Santa Creu i Sant Pau. The PCR was rapid, with a turnaround of just 1.5 hours. Decolonization of S. aureus carriers was carried out using nasal mupirocin and chlorhexidine gluconate bathing, which was started immediately. It was used for a 5 days and was usually continued throughout and after surgery.

Patients carrying MRSA received teicoplanin as optimal surgical antimicrobial prophylaxis instead of cefazolin. The intervention did not interfere with the timing of surgery. The study’s principal outcomes were overall incidence of prosthetic joint infections and the incidence of those specifically caused by S. aureus and MRSA.

The researchers compared findings regarding these outcomes over 5 consecutive years of the intervention to outcomes during 4 consecutive years prior to the intervention, which started in 2016.

During 2016-2020, from 22% to 31% of the overall number of patients requiring hip hemiarthroplasty were referred from long-term care facilities. From 25% to 29% of these patients tested positive for S. aureus on PCR, and of these, 33%-64% had MRSA.

There were 772 surgical procedures from 2012 to 2015 and 786 from 2017 to 2020.

Prior to the intervention, over the years 2012-2014, S. aureus caused 36%-50% of prosthetic joint infections; 25%-100% of the S. aureus infections were MRSA. This decreased significantly after the intervention.

During 2016-2020, there was an average of 14 prosthetic joint infections (1.5%), compared to 36 (4.7%) in 2012-2015 (P < .001). Similarly, the incidence of prosthetic joint infections due to S. aureus dropped to 0.3% from 1.8% (P < .002). The incidence of MRSA prosthetic joint infections was 0.3% for 2016-2020, versus 1.2% for 2012-2015 (P = .012).

The years 2018, 2020, and 2021 each saw one case of infection due to MRSA. They were most likely due to “the intervention not being performed properly in all cases,” said Dr. Benito.

A prosthetic joint infection is very serious for the patient. “It means reoperating, because antibiotics are not enough to clear the infection. The biofilm and pus of the infection need to be cleaned out, a new prosthesis is needed, after which more antibiotics are needed for around 2 months, which can be hard to tolerate, and even then, the infection might not be eradicated,” explained Dr. Benito. “Many of these people are old and frail, and mortality can be significant. Getting a prosthetic joint infection is catastrophic for these patients.”

Dr. Benito and Dr. Rodríguez-Baño have disclosed no relevant financial relationships.

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

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – Two-thirds of antibiotic prescriptions written for Black patients and more than half of antibiotic prescriptions for Hispanic/Latinx patients are inappropriate, according to data from a study of antibiotic prescribing habits in U.S. doctors’ offices, hospital clinics, and emergency departments.

Eric Young, PharmD, PhD, from the University of Texas at Austin, and UT Health, San Antonio, presented his work as a poster at the 32nd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022.

“We were really surprised mainly by the racial findings, because Black patients have the highest overall and the highest inappropriate prescribing of antibiotics,” he told this news organization. “There was also a difference seen for age [across all ethnicities].”

Pediatric patients were found to have high overall prescribing but, notably, the lowest inappropriate prescribing among all the patient groups, reported Dr. Young. “This is interesting because oftentimes we think the more antibiotics are prescribed, then surely the greater the inappropriate prescribing would be too, but pediatricians actually have one of the lowest rates of inappropriate antibiotic prescribing. They do a great job.”

The study included more than 7 billion patient visits, 11.3% of which involved an antibiotic prescription.

The rate of antibiotic prescribing was 122 per 1,000 visits in Black patients and 139 per 1,000 visits in Hispanic patients, while in White patients, the rate was 109 per 1,000 visits. The rate was 114 per 1,000 visits in patients younger than 18 years and 170 per 1,000 visits in females.

Dr. Young found that almost 64% of antibiotic prescriptions written for Black patients and 58% for Hispanic patients were inappropriate. For White patients, the rate of inappropriate antibiotic prescribing was 56%. Similarly, 74% of prescriptions dispensed to patients aged 65 years and older and 58% to males were deemed inappropriate.

Kajal Bhakta, PharmD, BCACP, ambulatory care clinical pharmacist, University Health System, UT Health Science Center San Antonio, who was not involved in the study, pointed out that antibiotics are frequently prescribed without confirmation of an infection, owing to the fact that the verification process may delay care, especially in the outpatient setting.

Dr. Bhakta said that overprescribing in the elderly population and in certain ethnic groups was “likely due to socioeconomic and cultural factors. These prescribing methods may lead to unnecessary drug side effects and/or antimicrobial resistance.”

Regarding the patient-doctor consultation process, she pointed out that “older patients may have trouble describing their symptoms, and when those symptoms remain unresolved, providers may be more inclined to prescribe antibiotics to help.”

Sometimes overprescribing can occur because of the logistics involved in getting to the doctor’s office in the outpatient setting. “Sometimes patients struggle with transportation, as two separate trips to the doctor and pharmacy may not be feasible. Additionally, these same patients may have limited access to health care and therefore may use an urgent care facility for their acute infection–like symptoms,” Dr. Bhakta explained.

Dr. Young, who is of Asian descent, first became interested in disparities in health care when he noticed that ethnic minority groups showed greater hesitancy toward COVID-19 vaccination. “I noticed that there weren’t many Asians involved in previous trials and realized at this point that disparities were rampant.”

Dr. Young had been involved in investigating the overall use and the inappropriate use of antibiotics across the whole U.S. population when his interest in health disparities prompted him to study these patterns in specific demographic groups.

“Most previous data are derived from inpatient studies where the physician is giving the antibiotics,” said Dr. Young, who looked specifically at outpatient prescribing.

Dr. Young used prescribing data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey, which covers more than 5.7 billion adult (aged 18 and older) and 1.3 billion child visits to outpatient practices between 2009 and 2016 across all 50 U.S. states and Washington, D.C.

He gathered patient data on ICD-9-CM and ICD-10 diagnostic codes for infections and for diagnoses that “appeared like infections.” All of the patients who were included had received at least one oral antibiotic. Antibiotic prescribing was defined as visits that included an antibiotic per 1,000 total patient visits.

On the basis of previous research, Dr. Young and his colleagues then determined whether each antibiotic prescription was appropriate, possibly appropriate, or inappropriate. Patient demographics included age (younger than 18 years, 18-64 years, and older than 64 years), sex (male or female), race, and ethnicity (White, Black, more than one race, Hispanic/Latinx, and other). These data were used to evaluate overall and inappropriate use.

“The health care community needs to be really careful with the judicious use of antibiotics,” Dr. Young said. “We have good guidelines on antimicrobial stewardship both in the inpatient and outpatient settings, but sometimes we overlook the disparities and cultural implications held by some patients.”

Typical examples of socioeconomic and cultural factors at play included patients not being able to afford the antibiotics, having limited access to care, or not returning for a follow-up visit for whatever reason.

“Patients of Black and Hispanic descent often don’t have the same degree of established care that many White patients have,” Dr. Young noted.

In the future, Dr. Young wants to conduct research into whether patients are actually taking their prescribed antibiotics, as well as their outcomes. For example, he would like to investigate whether rates of antibiotic resistance or Clostridioides difficile infection are higher among Black patients.

Dr. Young and Dr. Bhakta have disclosed no relevant financial relationships.

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

LISBON – During the pandemic, critical and acute care hospitals with medium and high rates of antimicrobial resistance (AMR) showed significant increases in antibiotic prescriptions and longer durations of antibiotic treatment among all hospital admissions, and also in those patients who were bacterial culture negative, according to a large U.S.-based study.

The analysis across 271 U.S. hospitals also showed that AMR rates were significantly higher for pathogens during the pandemic period, compared with the prepandemic period in patients who were tested for SARS-CoV-2, and highest in SARS-CoV-2–positive patients.

More than a third of SARS-CoV-2–positive patients who were prescribed antibiotics were bacterial culture negative.

Findings of the study were presented by Vikas Gupta, PharmD, director of medical affairs at medical technology firm Becton Dickinson, at this year’s European Congress of Clinical Microbiology & Infectious Diseases. He conducted the study jointly with Karri Bauer, PharmD, from Merck Sharp & Dohme, Kenilworth, N.J., and colleagues.

“There are differences in AMR that go beyond COVID-positive admissions,” Dr. Gupta told this news organization. “There is opportunity for improvement especially with those hospitalized patients who had a negative culture result, or no culture collected.”

“We found a higher percentage of COVID-positive admissions that were prescribed antibacterial therapy even in those having [tested negative for bacteria] or no culture result,” said Dr. Gupta. “Our data also shows that the percentage of admissions with duration of antibacterial therapy over 3 days was significantly higher in COVID-positive but culture-negative/no culture patients, compared to other groups evaluated.”

Of all admissions prescribed antibiotics during the pandemic, 57.8% of SARS-CoV-2–positive patients were prescribed antibiotics whereas 88.1% of SARS-CoV-2–positive admissions were bacterial culture negative/no culture. Overall, prepandemic, 35% of admissions were prescribed antibiotics.

Duration of antibiotic therapy in the prepandemic era was an average of 3.5 days, compared with an average of 3.8 days overall in the pandemic and 5.7 days in patients who tested positive for SARS-CoV-2. Similarly, the percentage of patients who were bacterial culture negative or had no culture and received antibiotic therapy for more than 72 hours was 17.6% in the prepandemic era, compared with 19.2% overall in the pandemic era, and 41.1% in patients who tested positive for COVID-19.  

Dr. Gupta and Dr. Bauer wanted to look at all patients admitted to hospitals segmented by SARS-CoV-2 positive, negative, and not tested, to get a sense of how much antibiotic use there was and how long patients were on antibiotics. “We ultimately want to optimize and not overuse antibiotics and prescribe them for right period of time,” said Dr. Gupta.

“To date, there has been no conclusive evidence about the suggestion that the pandemic has led to increased AMR rates, so we aimed to evaluate the pandemic’s impact on AMR and antibiotic use across U.S. hospitals,” he explained.

The multicenter, retrospective cohort analysis made use of BD’s infection surveillance platform (BD HealthSight Infection Advisor with MedMined Insights) and was conducted across 271 U.S. critical access/acute care facilities, representing approximately 10%-13% of U.S. hospital admissions. It included all hospitalized patients with more than 1 day of in-patient admission. Patients were considered SARS-CoV-2 positive by polymerase chain reaction test or antigen test either 7 days or less prior to or within 14 days of admission.

Patients were categorized as hospitalized during the “prepandemic” period (July 1, 2019 through February 29, 2020) and the “pandemic” period (March 1, 2020 through Oct. 30, 2021) and were stratified based on their SARS-CoV-2 result. 

Investigators included all hospital admissions with an AMR event (first positive culture for select gram-negative or gram-positive pathogens that were reported as nonsusceptible across blood, urine, respiratory, intra-abdominal, skin/wound, and other sources).

The investigators calculated AMR rates at the patient-admission level and defined per 100 admissions. Also, they further evaluated AMR rates based on community onset (defined as culture collected ≤2 days from admission) or hospital onset (>2 days from admission). Finally, AMR rates were determined according to whether they related to prepandemic or pandemic periods. 

Hospitals were also categorized according to their AMR rates as low (<25%), medium (25%-75%), and high (>75%). 

Overall AMR rates were lower in the pandemic period, compared with the prepandemic period. However, reported Dr.Gupta, for hospital-onset pathogens specifically, AMR rates were significantly higher overall in the pandemic period and mostly driven by admissions tested for SARS-CoV-2 (whether positive or negative).

Hospitals with high AMR rates also tended to have more SARS-CoV-2 positive admissions (6.1% in high-AMR hospitals vs. 3% in low-AMR hospitals). The highest antibiotic-prescribing rates and highest duration of antibiotic use was also seen in those hospitals with highest AMR rates. 

Of the SARS-CoV-2 patients who were bacterial culture negative/no culture and were prescribed antibiotics, 36.5% were in hospitals with a high AMR rate. “Roughly one-third of patients without culture evidence of a bacterial infection were prescribed antibiotics in hospitals with a high AMR rate,” said Dr. Gupta.

The researchers wanted to tease out whether hospitals with high, moderate, or low AMR rates look different with respect to antibiotic-prescribing patterns. During the pandemic period, they found that hospitals with high and medium AMR rates experienced significant increases in antibiotic prescriptions and longer durations. Prepandemic, the overall hospital-onset AMR rate was 0.8 per 100 admissions, whereas during the pandemic this rose to 1.4 per 100 admissions in high-AMR hospitals and dropped to 0.4 in low-AMR hospitals.

SARS-CoV-2–positive admission rates were higher in facilities with medium (5.6%) and high AMR (6.1%) rates than those with low (3%) AMR rates. “We found that those with medium and high AMR rates were more likely to have COVID-positive admissions than facilities with low AMR rates,” Dr. Gupta said. “It appears as if COVID is contributing to AMR in the facilities.”

Asked for independent comment, Jason C. Gallagher, PharmD, BCPS, clinical professor at Temple University School of Pharmacy in Philadelphia, said in an interview, “It is not surprising that there was more antimicrobial resistance in patients with COVID than those without. Even though antibiotics do not work for COVID, they are often prescribed, and antibiotic use is a major risk factor for antimicrobial resistance. This is likely because clinicians are sometimes concerned about coinfections with bacteria (which are rare) and because hospitalized patients with severe COVID can acquire other infections as they are treated.”
 

Antibiotic stewardship programs

Antibiotic stewardship programs have been highly stressed during the pandemic, so the researchers hope their data support the need for better antibiotic stewardship practices during pandemic surges when control is more challenging.

Dr. Gupta explained that they were seeing interesting associations that can inform antimicrobial stewardship programs and teams. “We are not trying to imply causality,” he stressed.

It is a common practice for stewardship teams to evaluate the need for continuation of antibiotic therapy at 3 days, especially in patients who are culture negative or did not have a culture collected.

“Antibiotic time-out at 3 days is a recommended practice to evaluate for continuing antibiotic therapy based on the patient’s condition and culture results,” he said. “This is what made our study unique because we wanted to look at what percentage of admissions were prescribed antibiotics beyond 3 days and compare to the prepandemic period.”

Session moderator Evangelos J. Giamarellos-Bourboulis, MD, PhD, an assistant professor of internal medicine and infectious diseases, University of Athens, Greece, thanked Dr. Gupta for his “eloquent presentation” and sought to clarify whether the data “refer to antimicrobial use that was empirical or whether use was in hospitals with high AMR rates, or whether the approach was driven through microbiology?”

Dr. Gupta replied that this was why they evaluated the negative-culture and no-culture patients. “We wanted to get a measure of antibacterial use in this population too,” he said. “Definitely, there is empirical therapy as well as definitive therapy, but I think the negative and no-culture group provide a reference point where we see similar signals and trends to that of the overall population.”

An audience member also addressed a question to Dr. Gupta: “Did you look at the patient population, because in many cases, during COVID, these patients may have been more severe than in the prepandemic period?”

Dr. Gupta replied: “In our manuscript we’ve done an analysis where we adjusted for patient-level facility and regional-level factors. There are definitely differences in the patient populations but overall, these are pretty sick patients when we look at the level of severity overall.”

Dr. Gupta is an employee of and a shareholder in Becton Dickinson. Dr. Bauer is an employee of and a shareholder in Merck. Dr. Gallagher consults for many pharmaceutical companies including Merck.

Dr. Giamarellos-Bourboulis disclosed honoraria (paid to the University of Athens) from Abbott CH, Brahms Thermo Fisher GMBH Germany, GlaxoSmithKline, and Sobi; serving as a consultant for Abbott CH, Fab’nTech, InflaRx GmbH, UCB, Sobi, and Xbiotech; research grants (paid to the Hellenic Institute for the Study of Sepsis) from Abbott CH, BioMerieux France, Johnson & Johnson, MSD, Sobi, Thermo Fisher Brahms GmbH; and EU research funding: Horizon 2020 ITN European Sepsis Academy (granted to the University of Athens); Horizon 2020 ImmunoSep and RISinCOVID (granted to the Hellenic Institute for the Study of Sepsis); Horizon Health EPIC-CROWN-2 (granted to the Hellenic Institute for the Study of Sepsis).

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Black and senior patients are more likely to be overprescribed antibiotics, according to a new study of 7 billion trips to health care centers – findings that doctors say warrant a further look into unequal prescription practices.

Researchers at the University of Texas Health Science Center found that 64% of antibiotic prescriptions to Black patients and 74% of antibiotic prescriptions to patients aged 65 years and older were deemed inappropriate. White patients, meanwhile, received prescriptions that were deemed inappropriate 56% of the time.

Most of those prescriptions were written for conditions like nonbacterial skin problems, viral respiratory tract infections, and bronchitis – none of which can be treated with antibiotics.

The study – which used data from visits to U.S. doctors’ offices, hospitals, and EDs – will be presented at the 2022 European Congress of Clinical Microbiology & Infectious Diseases in Lisbon.

Researchers also found that 58% of antibiotic prescriptions to patients with a Hispanic or Latin American background were also not appropriate for use.

“Our results suggest that Black and [Hispanic/Latino] patients may be not be properly treated and are receiving antibiotic prescriptions even when not indicated,” researcher Eric Young, PharmD, said in a news release.

Doctors typically will prescribe an antibiotic if they fear a patient’s symptoms may lead to an infection, Dr. Young said. This is particularly true if the doctor believes a patient is unlikely to return for a follow-up, which, he says, “more frequently happens in minority populations.”

The Centers for Disease Control and Prevention estimates that at least 30% of outpatient antibiotic prescriptions are not needed, and up to 50% of antibiotics prescribed are either unnecessary or the wrong type and/or dosage.

Overprescribing of antibiotics has long plagued the medical field. In 2015, the administration of then-President Barack Obama released a National Action Plan for Combating Antibiotic-Resistant Bacteria, with a goal to cut unneeded outpatient antibiotic use by at least half by 2020.

When antibiotics are overused, bacteria that infect us evolve to become stronger and defeat the drugs meant to save us.

Though the findings still need more study, at first glance they provide a concerning but unsurprising look at health inequities, said Rachel Villanueva, MD, president of the National Medical Association, the leading organization representing doctors and patients of African descent.

“We do know that these kind of inequities have existed for a long time in our society,” said Dr. Villanueva, a clinical assistant professor at the New York University. “They’re not new and have been well documented for many, many years. But this deserves further research and further evaluation.”

“This is just the first step – we need to do some more evaluation on how different communities are treated in the health care system. Why is this occurring?”

For patients 65 and older, it may be less about bias and more about having a hard time diagnosing certain conditions within that population, said Preeti Malani, MD, a professor of infectious diseases at the University of Michigan, Ann Arbor, and director of the National Poll on Healthy Aging.

For example, she said, some older patients may have a harder time describing their symptoms. In some cases, doctors may give these patients a prescription to fill in case the issue does not clear up, because it could be harder for them to get back into the office.

“Sometimes it’s hard to know exactly what’s going on,” Dr. Malani said. “Something I’ve done in my own practice in the past is say, ‘I’m giving you a prescription, but I don’t want you to fill it yet.’”

Dr. Malani said inappropriately prescribing antibiotics can be especially dangerous for people 65 and older because of drug interactions and complications like Achilles tendon rupture and a Clostridioides difficile infection, which can arise after antibiotic use.

“We need more information on what drives this in older adults,” she said.

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

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

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

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

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

Antibiotics are among the most commonly prescribed medications in both outpatient and hospital settings. Global efforts at curbing antibiotic-resistant strains have prompted clinicians to pursue better stewardship, whereby they limit their prescribing of such medications to those who truly need them.

Yet there’s another possible means of addressing antibiotic resistance – using dietary interventions to reduce the gastrointestinal complaints that so often accompany the use of antibiotics: vomiting, nausea, diarrhea, bloating/indigestion, abdominal pain, and loss of appetite. Far from being a mere nuisance, these complications can have major ramifications.

“Often [these side effects] will result in people stopping an antibiotic they need or taking a second- or third-generation one, which potentially causes even more problems with resistance,” explained Daniel J. Merenstein, MD, a professor of family medicine at Georgetown University, Washington, who has conducted multiple trials on antibiotic stewardship and probiotics.

And it’s not just clinicians who would like to find a way around these common complaints. On lifestyle blogs such as Livestrong and Goop, medical news websites, and via academic institutions, patients can learn how the right probiotic supplement or certain fermented or high-fiber foods, for example, might spare them the upset stomach that often accompanies a course of antibiotics.

Yet according to experts in the field, there are notable questions to be answered about whether there’s evidence to support this approach.

The cost of GI discomfort

Pinpointing the exact manner by which antibiotics upend GI tracts is a complex task, according to Gail Cresci, PhD, RD, a microbiome researcher in the department of pediatric gastroenterology, hepatology, and nutrition and director of nutrition research at the Cleveland Clinic.

“A lot of different mechanisms can go awry,” Dr. Cresci said. “But normally, the good microbes are there to help keep the balance, so when that balance is gone, the pathogens can take over and lead to this disruption.”

According to Lynne V. McFarland, PhD, a recently retired infectious disease epidemiologist who now serves as a private consultant, such complications can have substantial ramifications for patients and health care systems.

“If you’re an inpatient and develop antibiotic-associated diarrhea, it usually increases the length of stay from 8 to 20 days. It also increases the cost of care. And small children who have this can get severely dehydrated, which can become life threatening.”

Proponents of probiotics

Several of the researchers who were interviewed believe there’s convincing evidence supporting probiotics for the treatment of common antibiotic-related GI complaints. In many instances, they were involved in the studies themselves.

During Dr. McFarland’s 4-decade career in probiotics research, she has participated in early animal studies with strains such as Saccharomyces boulardii and was involved in meta-analyses of their role in Clostridioides difficile infection and associated diarrhea and even as a potential GI intervention for COVID-19 patients (Antibiotics (Basel). 2021 Apr 9;10(4):408).

In mouse model studies from 2013 and 2018, Dr. Cresci and colleagues showed that the probiotic strains Lactobacillus GG and Faecalibacterium prausnitzii reduced the structural gut changes that lead to antibiotic-associated diarrhea and minimized the risk of C. difficile infection.

In a 2021 randomized controlled trial led by Merenstein, healthy participants were given a trial of amoxicillin/clavulanate (days 1-7) in conjunction with either yogurt containing the probiotic Bifidobacterium animalis subsp lactis BB-12 or control yogurt (days 1-14). After assessing feces samples over a 30-day period, they found that those who received the probiotic yogurt had a significantly smaller decrease in short-chain fatty acid levels and a more stable taxonomic microbiota profile than control persons.

Dr. Merenstein said that, on the basis of results such as these and others, he’s comfortable being relatively definitive about the value of probiotics.

“I believe it’s close to standard of care that if you’re prescribing antibiotics, especially for more than 7 days, you really need to put people on probiotics that have been studied, simply because the evidence is robust enough now,” he said.

Even for proponents, there are caveats

However, all the researchers recommending the use of probiotics did so with caveats. First and foremost, they advise clinicians that the term “probiotics” is an imprecise catchall and is essentially meaningless.

“A lot of products label themselves as probiotic. It’s a great marketing scheme, but many of the products out there aren’t really probiotics; they’re not proven with randomized control trials and don’t have the scientific background,” said Dr. McFarland. “We’ve found that the efficacy is extremely strain specific and disease specific. A strain may work for one disease and not work for another.”

In 2018, Dr. McFarland coauthored an evidence-based practical guide to help clinicians and patients identify the specific strain that works in certain indications. Dr. Cresci recommends that clinicians consult websites such as Probiotics.org or the National Institutes of Health’s database to find the strains that have been proven to work in well-designed clinical trials.

There was also agreement that, to date, the most robust data support probiotics for the treatment of antibiotic-associated diarrhea.

Although the optimal timing of probiotics is a subject of debate, most proponents agreed that the general rule is “the sooner the better.”

Dr. McFarland recommended incorporating probiotics within 24 hours of starting an antibiotic “because the damage done to your GI tract microbiome is pretty quick, and the probiotics work best if they’re established before major disruption occurs.” She added that patients should continue taking probiotics for 2-8 weeks after stopping antibiotics.

“It takes a long time for your normal flora to get restored,” she said. “It’s best to cover your bases.”

For others, the evidence is not definitive

Opinions on the value of probiotics to combat antibiotic-related GI side effects are divergent, though.

“I would not recommend the routine use of probiotics, and certainly not in the prevention of C. difficile or antibiotic-related diarrhea,” said David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School, Norfolk. “I think the evidence does not support that, and I stand strongly on that recommendation.”

Dr. Johnson cited the 2020 guidelines from the American Gastroenterological Association, which offer only a conditional recommendation for the use of specific probiotics and only in preventing antibiotic-associated C. difficile infection.

Geoffrey A. Preidis, MD, PhD, an assistant professor of pediatrics in the section of gastroenterology, hepatology, and nutrition at Baylor College of Medicine, Houston, served as a coauthor of the AGA’s guidelines. He noted that after reviewing 39 published trials of approximately 10,000 patients given probiotics while receiving antibiotics, the authors “did find some evidence that specific probiotics might decrease the risk of C. difficile diarrhea, but the quality of that evidence was low.”

Dr. Preidis attributed this to the lack of well-designed multicenter trials that can isolate the effects of certain strains and determine their benefit in this application.

“The majority of published trials have not reported safety data as rigorously as these data are reported in pharmaceutical trials, so the risk of side effects could be higher than we think,” said Dr. Preidis. “As living microbes, probiotics can move from the intestines into the bloodstream, causing sepsis. Contamination in the manufacturing process has been reported. There might be other long-term effects that we are not yet aware of.”

When asked to characterize the available data on probiotics, Dr. Johnson replied, “I’d generally label it, ‘caveat emptor.’ ”

Dr. McFarland agreed that the field would benefit from better-designed studies and called out meta-analyses that pool outcomes with various strains for particular criticism.

“When researchers do that, it’s no longer valid and shouldn’t have been published, in my opinion,” she told this news organization.

‘Antibiotic diets’ as a possible approach

A compromise between the two sides may be the so-called antibiotic diet. The theory behind such diets is that foods and beverages with biome-boosting properties may be a risk-free intervention that patients can adopt to alleviate antibiotic-related side effects.

“You want your diet to include more soluble fibers to help support the good bacteria, particularly when you’re taking antibiotics,” said Dr. Cresci. “You can get this through eating fresh fruits and vegetables, whole grains, and foods that have more prebiotic, like potatoes. You can also eat fermented food, such as kefir, kombucha, kimchi, and yogurt, so you’re adding more beneficial bacteria into your intestinal tract.”

There is ample published evidence that such foods can boost microbiome diversity and decrease inflammation, including a July 2021 study in Cell. However, the protection this may confer while taking antibiotics isn’t known. Establishing a clear role for the efficacy of such interventions is made additionally difficult by the well-established limitations of conducting dietary clinical trials.

Dr. Merenstein said that there is no compelling evidence that antibiotic-related complications can be offset by changing what goes onto our dinner plates. He joked: “We can’t say, ‘Here’s amoxicillin for your ear infection, now make sure you increase your fermented food, fiber, and water.’ ”

Dr. Johnson said he’s intrigued by studies of prebiotics – fibers that boost beneficial bacteria in the GI system.

“I would love to have more findings about prebiotic identification; that is, things we could do in a healthy way to keep the gut balanced while it’s subject to a change with antibiotics,” he said. “We’re just not there yet.”

Dr. Johnson added that he generally recommends that patients taking antibiotics eat “a bland diet, avoiding things that may have been provocative in the past.”

If patients are already enjoying foods with microbiome-boosting reputations, Dr. Johnson sees “very little downside to continuing that [while on antibiotics].” However, he noted that the period in which you’re taking antibiotics isn’t ideal for trying new foods, given the lack of experience with how the gut bacteria will react.

There are data about foods to avoid while taking antibiotics, which generally fall in line with common dietary knowledge. Many patients may know not to drink grapefruit juice with certain medications, but it’s worth a reminder. Certain antibiotics may also require delaying or avoiding dairy products, although this does not apply to yogurt.

A fiber-deficient diet can aggravate microbiota collapse following antibiotics. In a 2020 study, researchers showed that people on a high-fat diet who were using antibiotics were 8.6 times more likely to have preinflammatory bowel disease than those eating low-fat foods and who had no recent history of antibiotic use. Mouse model data from the same study indicated that poor diet and antibiotics may have worked in conjunction to reduce oxygen in the gut.

Dr. McFarland noted that building a healthy microbiome is a lifelong pursuit and that several factors (for example, environmental or genetic) are out of individuals’ hands. The general public might want a quick fix – ironically, one of the main drivers behind their requesting and receiving antibiotics when they’re not indicated – but it’s likely not available to them.

“You can’t eat one salad and suddenly have a healthy gut, unfortunately.”

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

Third-party vendor physicians appear to be more much more likely than their system-employed counterparts to prescribe antibiotics during acute care telehealth visits for acute respiratory infection (ARI), according to a study in the Journal of Telemedicine and Telecare.

As health systems expand their direct-to-consumer (DTC) virtual care, the quality of that care seems to vary, write the authors. Patients with ARI symptoms make up about one-third of virtual visits. Prescribing practice is a commonly cited measure of care quality for ARI, which is usually viral and rarely benefits from antibiotics.

“When providing care through telehealth, hospital-affiliated emergency physicians practiced better antibiotic stewardship than vendor-supplied, non–hospital-affiliated physicians,” lead study author Kathleen Li, MD, MS, a clinical lecturer in the department of emergency medicine at the University of Michigan, Ann Arbor, told this news organization.

“We had a sense that a difference existed, but the magnitude of the difference was larger than expected,” she said.

Dr. Li and her colleagues retrospectively analyzed on-demand telehealth visits available to health system employees and dependents of a large urban academic health system from March 2018, when the service began, through July 2019.

All 16 affiliated physicians providing ARI care were board-certified in emergency medicine, compared with 2 (8%) of the 25 unaffiliated (vendor-employed) physicians. Most unaffiliated physicians were known to be board-certified in family medicine, internal medicine, or pediatrics.

Unaffiliated physicians were not given access to the health system’s electronic medical record. Instead, all their patient histories, exams, assessments, plans, impressions, and discharge instructions were scanned into the electronic medical record system by other staff the next day.
 

Unaffiliated doctors were more than twice as likely to prescribe antibiotics

The researchers extracted data on all 257 virtual ARI visits from the electronic health record system, including prescriptions and medication therapeutic class. They performed multivariable logistic regression, adjusting for patient age and time of visit (weekday vs. weekend; day vs. overnight).

Antibiotic prescription rates were similar between weekday and weekend visits, and between day and night visits. Regardless of provider status, older patients were more likely to be prescribed antibiotics (P = .01). 

Overall, affiliated physicians prescribed antibiotics during 18% of visits, whereas vendor physicians prescribed antibiotics during 37% of visits. After adjustments, the odds were 2.3 times higher that a patient in a telehealth visit with a vendor provider would be prescribed antibiotics (95% confidence interval, 1.1-4.5).

The predicted antibiotic prescribing rate for ARI was 19% (95% confidence interval, 13%-25%) for affiliated providers vs. 35% (95% CI, 22%-47%) for unaffiliated providers, an average marginal effect of 15% (95% CI, 2%-29%). The difference was even greater (average marginal effect 20%, 95% CI, 4%-35%) when children and patients over 65 were excluded.
 

Consistent, high-quality care and antibiotic stewardship are needed in all settings

Three experts who were not involved in the study commented on the study.

Joshua W. Elder, MD, MPH, MHS, medical director of Telehealth Express Care (direct-to-consumer telemedicine) at UC Davis Health in Sacramento, Calif., said, “An important unanswered question is how factors such as communication (policy and procedures, practice guidelines), connection (electronic health records), and reimbursement and incentives that health system and vendor-based providers received impacted this outcome.

“As the volume of virtual practices grows, most health systems will need to create a hybrid between health-system-employed and vendor-and/or-payer-supplied physicians,” he added. “Finding ways to create similar quality and outcomes will be essential in the evolving digital health infrastructure being developed.”

Charles Teixeira, DO, an infectious disease specialist at the Medical University of South Carolina in Charleston, said that this study highlighted the need to consistently provide high-quality, evidence-based care regardless of the encounter setting.

“It was important to compare the prescribing practices for commonly used medications, especially those as important as antibiotics,” he added. “Overprescribing antibiotics can have a progressive, long-term effect on a community and increase the risk for patients to develop multidrug-resistant bacteria.”

Jeffrey A. Linder, MD, MPH, the chief of general internal medicine and geriatrics in the department of medicine at Northwestern University in Chicago, commended the authors for investigating the quality of telehealth.

“The major limitation,” he found, “is that the investigators lumped all ARI visits – including those that are potentially antibiotic appropriate (e.g., otitis media, pharyngitis, sinusitis), those that are non–antibiotic appropriate (e.g., bronchitis, influenza, laryngitis, URI, viral syndrome), and those that are nonspecific symptoms (e.g., cough, congestion, fever, sore throat) – into the same category.”

No clinical information was collected or presented that would enable the reader to tell if these two groups of physicians were evaluating different patient populations or even if they just diagnosed patients differently,” he added.

“Our study did not delve into why we saw the difference,” Dr. Li explained. “Exploring potential reasons further will have important implications for how to optimally deliver care via telehealth.”

All authors and independent experts have disclosed no relevant financial relationships. The study received no financial support.

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

Third-party vendor physicians appear to be more much more likely than their system-employed counterparts to prescribe antibiotics during acute care telehealth visits for acute respiratory infection (ARI), according to a study in the Journal of Telemedicine and Telecare.

As health systems expand their direct-to-consumer (DTC) virtual care, the quality of that care seems to vary, write the authors. Patients with ARI symptoms make up about one-third of virtual visits. Prescribing practice is a commonly cited measure of care quality for ARI, which is usually viral and rarely benefits from antibiotics.

“When providing care through telehealth, hospital-affiliated emergency physicians practiced better antibiotic stewardship than vendor-supplied, non–hospital-affiliated physicians,” lead study author Kathleen Li, MD, MS, a clinical lecturer in the department of emergency medicine at the University of Michigan, Ann Arbor, told this news organization.

“We had a sense that a difference existed, but the magnitude of the difference was larger than expected,” she said.

Dr. Li and her colleagues retrospectively analyzed on-demand telehealth visits available to health system employees and dependents of a large urban academic health system from March 2018, when the service began, through July 2019.

All 16 affiliated physicians providing ARI care were board-certified in emergency medicine, compared with 2 (8%) of the 25 unaffiliated (vendor-employed) physicians. Most unaffiliated physicians were known to be board-certified in family medicine, internal medicine, or pediatrics.

Unaffiliated physicians were not given access to the health system’s electronic medical record. Instead, all their patient histories, exams, assessments, plans, impressions, and discharge instructions were scanned into the electronic medical record system by other staff the next day.
 

Unaffiliated doctors were more than twice as likely to prescribe antibiotics

The researchers extracted data on all 257 virtual ARI visits from the electronic health record system, including prescriptions and medication therapeutic class. They performed multivariable logistic regression, adjusting for patient age and time of visit (weekday vs. weekend; day vs. overnight).

Antibiotic prescription rates were similar between weekday and weekend visits, and between day and night visits. Regardless of provider status, older patients were more likely to be prescribed antibiotics (P = .01). 

Overall, affiliated physicians prescribed antibiotics during 18% of visits, whereas vendor physicians prescribed antibiotics during 37% of visits. After adjustments, the odds were 2.3 times higher that a patient in a telehealth visit with a vendor provider would be prescribed antibiotics (95% confidence interval, 1.1-4.5).

The predicted antibiotic prescribing rate for ARI was 19% (95% confidence interval, 13%-25%) for affiliated providers vs. 35% (95% CI, 22%-47%) for unaffiliated providers, an average marginal effect of 15% (95% CI, 2%-29%). The difference was even greater (average marginal effect 20%, 95% CI, 4%-35%) when children and patients over 65 were excluded.
 

Consistent, high-quality care and antibiotic stewardship are needed in all settings

Three experts who were not involved in the study commented on the study.

Joshua W. Elder, MD, MPH, MHS, medical director of Telehealth Express Care (direct-to-consumer telemedicine) at UC Davis Health in Sacramento, Calif., said, “An important unanswered question is how factors such as communication (policy and procedures, practice guidelines), connection (electronic health records), and reimbursement and incentives that health system and vendor-based providers received impacted this outcome.

“As the volume of virtual practices grows, most health systems will need to create a hybrid between health-system-employed and vendor-and/or-payer-supplied physicians,” he added. “Finding ways to create similar quality and outcomes will be essential in the evolving digital health infrastructure being developed.”

Charles Teixeira, DO, an infectious disease specialist at the Medical University of South Carolina in Charleston, said that this study highlighted the need to consistently provide high-quality, evidence-based care regardless of the encounter setting.

“It was important to compare the prescribing practices for commonly used medications, especially those as important as antibiotics,” he added. “Overprescribing antibiotics can have a progressive, long-term effect on a community and increase the risk for patients to develop multidrug-resistant bacteria.”

Jeffrey A. Linder, MD, MPH, the chief of general internal medicine and geriatrics in the department of medicine at Northwestern University in Chicago, commended the authors for investigating the quality of telehealth.

“The major limitation,” he found, “is that the investigators lumped all ARI visits – including those that are potentially antibiotic appropriate (e.g., otitis media, pharyngitis, sinusitis), those that are non–antibiotic appropriate (e.g., bronchitis, influenza, laryngitis, URI, viral syndrome), and those that are nonspecific symptoms (e.g., cough, congestion, fever, sore throat) – into the same category.”

No clinical information was collected or presented that would enable the reader to tell if these two groups of physicians were evaluating different patient populations or even if they just diagnosed patients differently,” he added.

“Our study did not delve into why we saw the difference,” Dr. Li explained. “Exploring potential reasons further will have important implications for how to optimally deliver care via telehealth.”

All authors and independent experts have disclosed no relevant financial relationships. The study received no financial support.

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

Third-party vendor physicians appear to be more much more likely than their system-employed counterparts to prescribe antibiotics during acute care telehealth visits for acute respiratory infection (ARI), according to a study in the Journal of Telemedicine and Telecare.

As health systems expand their direct-to-consumer (DTC) virtual care, the quality of that care seems to vary, write the authors. Patients with ARI symptoms make up about one-third of virtual visits. Prescribing practice is a commonly cited measure of care quality for ARI, which is usually viral and rarely benefits from antibiotics.

“When providing care through telehealth, hospital-affiliated emergency physicians practiced better antibiotic stewardship than vendor-supplied, non–hospital-affiliated physicians,” lead study author Kathleen Li, MD, MS, a clinical lecturer in the department of emergency medicine at the University of Michigan, Ann Arbor, told this news organization.

“We had a sense that a difference existed, but the magnitude of the difference was larger than expected,” she said.

Dr. Li and her colleagues retrospectively analyzed on-demand telehealth visits available to health system employees and dependents of a large urban academic health system from March 2018, when the service began, through July 2019.

All 16 affiliated physicians providing ARI care were board-certified in emergency medicine, compared with 2 (8%) of the 25 unaffiliated (vendor-employed) physicians. Most unaffiliated physicians were known to be board-certified in family medicine, internal medicine, or pediatrics.

Unaffiliated physicians were not given access to the health system’s electronic medical record. Instead, all their patient histories, exams, assessments, plans, impressions, and discharge instructions were scanned into the electronic medical record system by other staff the next day.
 

Unaffiliated doctors were more than twice as likely to prescribe antibiotics

The researchers extracted data on all 257 virtual ARI visits from the electronic health record system, including prescriptions and medication therapeutic class. They performed multivariable logistic regression, adjusting for patient age and time of visit (weekday vs. weekend; day vs. overnight).

Antibiotic prescription rates were similar between weekday and weekend visits, and between day and night visits. Regardless of provider status, older patients were more likely to be prescribed antibiotics (P = .01). 

Overall, affiliated physicians prescribed antibiotics during 18% of visits, whereas vendor physicians prescribed antibiotics during 37% of visits. After adjustments, the odds were 2.3 times higher that a patient in a telehealth visit with a vendor provider would be prescribed antibiotics (95% confidence interval, 1.1-4.5).

The predicted antibiotic prescribing rate for ARI was 19% (95% confidence interval, 13%-25%) for affiliated providers vs. 35% (95% CI, 22%-47%) for unaffiliated providers, an average marginal effect of 15% (95% CI, 2%-29%). The difference was even greater (average marginal effect 20%, 95% CI, 4%-35%) when children and patients over 65 were excluded.
 

Consistent, high-quality care and antibiotic stewardship are needed in all settings

Three experts who were not involved in the study commented on the study.

Joshua W. Elder, MD, MPH, MHS, medical director of Telehealth Express Care (direct-to-consumer telemedicine) at UC Davis Health in Sacramento, Calif., said, “An important unanswered question is how factors such as communication (policy and procedures, practice guidelines), connection (electronic health records), and reimbursement and incentives that health system and vendor-based providers received impacted this outcome.

“As the volume of virtual practices grows, most health systems will need to create a hybrid between health-system-employed and vendor-and/or-payer-supplied physicians,” he added. “Finding ways to create similar quality and outcomes will be essential in the evolving digital health infrastructure being developed.”

Charles Teixeira, DO, an infectious disease specialist at the Medical University of South Carolina in Charleston, said that this study highlighted the need to consistently provide high-quality, evidence-based care regardless of the encounter setting.

“It was important to compare the prescribing practices for commonly used medications, especially those as important as antibiotics,” he added. “Overprescribing antibiotics can have a progressive, long-term effect on a community and increase the risk for patients to develop multidrug-resistant bacteria.”

Jeffrey A. Linder, MD, MPH, the chief of general internal medicine and geriatrics in the department of medicine at Northwestern University in Chicago, commended the authors for investigating the quality of telehealth.

“The major limitation,” he found, “is that the investigators lumped all ARI visits – including those that are potentially antibiotic appropriate (e.g., otitis media, pharyngitis, sinusitis), those that are non–antibiotic appropriate (e.g., bronchitis, influenza, laryngitis, URI, viral syndrome), and those that are nonspecific symptoms (e.g., cough, congestion, fever, sore throat) – into the same category.”

No clinical information was collected or presented that would enable the reader to tell if these two groups of physicians were evaluating different patient populations or even if they just diagnosed patients differently,” he added.

“Our study did not delve into why we saw the difference,” Dr. Li explained. “Exploring potential reasons further will have important implications for how to optimally deliver care via telehealth.”

All authors and independent experts have disclosed no relevant financial relationships. The study received no financial support.

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