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A pill for C. difficile works by increasing microbiome diversity
CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.
The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.
The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.
“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”
Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
Study details
The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.
“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”
After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.
The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).
After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).
Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).
Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.
Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.
Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
Understanding how it works
To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.
At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.
The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.
“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.
Based on these results, Finch plans to launch a phase 3 trial soon, she said.
The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.
But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.
“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.
Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.
Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.
The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.
The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.
“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”
Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
Study details
The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.
“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”
After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.
The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).
After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).
Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).
Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.
Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.
Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
Understanding how it works
To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.
At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.
The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.
“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.
Based on these results, Finch plans to launch a phase 3 trial soon, she said.
The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.
But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.
“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.
Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.
Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CP101, under development by Finch Therapeutics, proved more effective than a placebo in preventing recurrent infections for up to 24 weeks.
The CP101 capsules contain a powder of freeze-dried human stools from screened donors. They restore natural diversity that has been disrupted by antibiotics, said Jessica Allegretti, MD, MPH a gastroenterologist at Brigham and Women’s Hospital in Boston.
The treatment offers an alternative to fecal microbiota transplant, which can effectively treat antibiotic-resistant C. difficile infections but is difficult to standardize and administer – and doesn’t have full approval from the U.S. Food and Drug Administration, she added.
“I think this marks a moment in this space where we’re going to have better, safer, and more available options for patients,” she said in an interview. “It’s exciting.”
Dr. Allegretti is an author on three presentations of results from PRISM3, a phase 2 trial of CP101. They will be presented this week at the annual meeting of the American College of Gastroenterology. These results extend out to 24 weeks, whereas the 8-week results of this trial were presented a year ago at the same meeting.
Study details
The study enrolled 198 people who received antibiotics for recurrent C. difficile infections. Some patients had two or more recurrences, while others had only one recurrence but were 65 years of age or older.
“That was a unique aspect of this study, to see the effect of bringing a therapy like CP101 earlier in the treatment paradigm,” said Dr. Allegretti. “You can imagine for an older, frail, or more fragile patient that you would want to get rid of this [infection] earlier.”
After waiting 2-6 days for the antibiotics to wash out, the researchers randomly assigned 102 of these patients to take the CP101 pills orally and 96 to take placebo pills, both without bowel preparation.
The two groups were not significantly different in age, gender, comorbidities, the number of C. difficile recurrences, or the type of test used to diagnose the infection (PCR-based vs. toxin EIA-based).
After 8 weeks, 74.5% of those given the CP101 pills had not had a recurrence, compared with 61.5% of those given the placebo. The difference was just barely statistically significant (P = .0488).
Sixteen weeks later, the effect endured, with 73.5% of the CP101 group and 59.4% of the placebo group still free of recurrence. The statistical significance of the difference improved slightly (P = .0347).
Drug-related emergent adverse events were similar between the two groups: 16.3% for the CP101 group vs. 19.2% for the placebo group. These were mostly gastrointestinal symptoms, and none were serious.
Some of the patients received vancomycin as a first-line treatment for C. difficile infections, and the researchers wondered if the washout period was not sufficient to purge that antibiotic, leaving enough to interfere with the effectiveness of CP101.
Therefore, they separately analyzed 40 patients treated with fidaxomicin, which they expected to wash out more quickly. Among these patients, 81% who received CP101 were free of recurrences, at 8 weeks and 24 weeks. This compared with 42.1% of those who received the placebo, at both time points. This difference was more statistically significant (P = .0211).
Understanding how it works
To understand better how CP101 achieves its effects, the researchers collected stool samples from the patients and counted the number of different kinds organisms in each sample.
At baseline, the patients had about the same number, but after a week the diversity was greater in the patients treated with CP101, and that difference had increased at week 8. The researchers also found much less diversity of organisms in the stools of those patients who had recurrences of C. difficile infection.
The diversity of microbes in the successfully treated patients appeared to have been introduced by CP101. Dr. Allegretti and colleagues measured the number of organisms in the stool samples that came from CP101. They found that 96% of patients colonized by the CP101 organisms had avoided recurrence of the C. difficile infections, compared with 54.2% of those patients not colonized by these microbes.
“We now have some microbiome-based markers that show us as early as week 1 that the patient is going to be cured or not,” Dr. Allegretti said.
Based on these results, Finch plans to launch a phase 3 trial soon, she said.
The data on colonization is interesting because it has not been found with fecal microbiota transplants, said Purna Kashyap, MBBS, codirector of the Microbiome Program at the Mayo Clinic College of Medicine in Rochester, Minn., who was not involved in the study.
But to better interpret the data, it would be helpful to know more about how the placebo and CP101 groups compared at baseline with regard to medications, immunosuppression, and antibiotics used to treat the C. difficile infections, Dr. Kashyap said. He was struck by the lower cure rate in the portion of the placebo group treated with fidaxomicin.
“Overall, I think these are exciting observations based on the data but require careful review of the entire data to make sense of [them], which will happen when it goes through peer review,” he told this news organization in an email.
Several other standardized microbiota restoration products are under development, including at least two other capsules. In contrast to CP101, which is made up of whole stool, VE303 (Vedanta Biosciences) is a “rationally defined bacterial consortium,” and SER-109 (Seres Therapeutics) is a “consortium of highly purified Firmicutes spores.” VE303 has completed a phase 2 trial, and SER-109 has completed a phase 3 trial.
Dr. Allegretti is a consultant for Finch Therapeutics, which funded the trial. Dr. Kashyap has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2021
Women with recurrent UTIs express fear, frustration
Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.
“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.
Findings from the study were published online Sept. 1 in The Journal of Urology.
“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
Six focus groups
Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.
From a qualitative analysis of all focus group transcripts, two main themes emerged:
- The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
- Resentment of the medical profession for the way it managed rUTIs.
The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.
These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.
Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.
In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
Improved management strategies
Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.
It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.
Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.
If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.
Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).
For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.
“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.
“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
Further commentary
Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.
Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.
She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.
“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.
Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.
“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.
Findings from the study were published online Sept. 1 in The Journal of Urology.
“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
Six focus groups
Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.
From a qualitative analysis of all focus group transcripts, two main themes emerged:
- The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
- Resentment of the medical profession for the way it managed rUTIs.
The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.
These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.
Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.
In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
Improved management strategies
Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.
It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.
Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.
If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.
Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).
For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.
“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.
“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
Further commentary
Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.
Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.
She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.
“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.
Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Fear of antibiotic overuse and frustration with physicians who prescribe them too freely are key sentiments expressed by women with recurrent urinary tract infections (rUTIs), according to findings from a study involving six focus groups.
“Here in our female pelvic medicine reconstructive urology clinic at Cedars-Sinai and at UCLA, we see many women who are referred for evaluation of rUTIs who are very frustrated with their care,” Victoria Scott, MD, Cedars-Sinai Medical Center, Los Angeles, said in an interview.
“So with these focus groups, we saw an opportunity to explore why women are so frustrated and to try and improve the care delivered,” she added.
Findings from the study were published online Sept. 1 in The Journal of Urology.
“There is a need for physicians to modify management strategies ... and to devote more research efforts to improving nonantibiotic options for the prevention and treatment of recurrent urinary tract infections, as well as management strategies that better empower patients,” the authors wrote.
Six focus groups
Four or five participants were included in each of the six focus groups – a total of 29 women. All participants reported a history of symptomatic, culture-proven UTI episodes. They had experienced two or more infections in 6 months or three or more infections within 1 year. Women were predominantly White. Most were employed part- or full-time and held a college degree.
From a qualitative analysis of all focus group transcripts, two main themes emerged:
- The negative impact of taking antibiotics for the prevention and treatment of rUTIs.
- Resentment of the medical profession for the way it managed rUTIs.
The researchers found that participants had a good understanding of the deleterious effects from inappropriate antibiotic use, largely gleaned from media sources and the Internet. “Numerous women stated that they had reached such a level of concern about antibiotics that they would resist taking them for prevention or treatment of infections,” Dr. Scott and colleagues pointed out.
These concerns centered around the risk of developing resistance to antibiotics and the ill effects that antibiotics can have on the gastrointestinal and genitourinary microbiomes. Several women reported that they had developed Clostridium difficile infections after taking antibiotics; one of the patients required hospitalization for the infection.
Women also reported concerns that they had been given an antibiotic needlessly for symptoms that might have been caused by a genitourinary condition other than a UTI. They also reported feeling resentful toward practitioners, particularly if they felt the practitioner was overprescribing antibiotics. Some had resorted to consultations with alternative practitioners, such as herbalists. “A second concern discussed by participants was the feeling of being ignored by physicians,” the authors observed.
In this regard, the women felt that their physicians underestimated the burden that rUTIs had on their lives and the detrimental effect that repeated infections had on their relationships, work, and overall quality of life. “These perceptions led to a prevalent mistrust of physicians,” the investigators wrote. This prompted many women to insist that the medical community devote more effort to the development of nonantibiotic options for the prevention and treatment of UTIs.
Improved management strategies
Asked how physicians might improve their management of rUTIs, Dr. Scott shared a number of suggestions. Cardinal rule No. 1: Have the patient undergo a urinalysis to make sure she does have a UTI. “There is a subset of patients among women with rUTIs who come in with a diagnosis of an rUTI but who really have not had documentation of more than one positive urine culture,” Dr. Scott noted. Such a history suggests that they do not have an rUTI.
It’s imperative that physicians rule out commonly misdiagnosed disorders, such as overactive bladder, as a cause of the patient’s symptoms. Symptoms of overactive bladder and rUTIs often overlap. While waiting for results from the urinalysis to confirm or rule out a UTI, young and healthy women may be prescribed a nonsteroidal anti-inflammatory drug (NSAID), such as naproxen, which can help ameliorate symptoms.
Because UTIs are frequently self-limiting, Dr. Scott and others have found that for young, otherwise healthy women, NSAIDs alone can often resolve symptoms of the UTI without use of an antibiotic. For relatively severe symptoms, a urinary analgesic, such as phenazopyridine (Pyridium), may soothe the lining of the urinary tract and relieve pain. Cystex is an over-the-counter urinary analgesic that women can procure themselves, Dr. Scott added.
If an antibiotic is indicated, those most commonly prescribed for a single episode of acute cystitis are nitrofurantoin and sulfamethoxazole plus trimethoprim (Bactrim). For recurrent UTIs, “patients are a bit more complicated,” Dr. Scott admitted. “I think the best practice is to look back at a woman’s prior urine culture and select an antibiotic that showed good sensitivity in the last positive urine test,” she said.
Prevention starts with behavioral strategies, such as voiding after sexual intercourse and wiping from front to back following urination to avoid introducing fecal bacteria into the urethra. Evidence suggests that premenopausal women who drink at least 1.5 L of water a day have significantly fewer UTI episodes, Dr. Scott noted. There is also “pretty good” evidence that cranberry supplements (not juice) can prevent rUTIs. Use of cranberry supplements is supported by the American Urological Association (conditional recommendation; evidence level of grade C).
For peri- and postmenopausal women, vaginal estrogen may be effective. It’s use for UTI prevention is well supported by the literature. Although not as well supported by evidence, some women find that a supplement such as D-mannose may prevent or treat UTIs by causing bacteria to bind to it rather than to the bladder wall. Probiotics are another possibility, she noted. Empathy can’t hurt, she added.
“A common theme among satisfied women was the sentiment that their physicians understood their problems and had a system in place to allow rapid diagnosis and treatment for UTI episodes,” the authors emphasized.
“[Such attitudes] highlight the need to investigate each patient’s experience and perceptions to allow for shared decision making regarding the management of rUTIs,” they wrote.
Further commentary
Asked to comment on the findings, editorialist Michelle Van Kuiken, MD, assistant professor of urology, University of California, San Francisco, acknowledged that there is not a lot of good evidence to support many of the strategies recommended by the American Urological Association to prevent and treat rUTIs, but she often follows these recommendations anyway. “The one statement in the guidelines that is the most supported by evidence is the use of cranberry supplements, and I do routinely recommended daily use of some form of concentrated cranberry supplements for all of my patients with rUTIs,” she said in an interview.
Dr. Van Kuiken said that vaginal estrogen is a very good option for all postmenopausal women who suffer from rUTIs and that there is growing acceptance of its use for this and other indications. There is some evidence to support D-mannose as well, although it’s not that robust, she acknowledged.
She said the evidence supporting the use of probiotics for this indication is very thin. She does not routinely recommend them for rUTIs, although they are not inherently harmful. “I think for a lot of women who have rUTIs, it can be pretty debilitating and upsetting for them – it can impact travel plans, work, and social events,” Dr. Van Kuiken said.
“Until we develop better diagnostic and therapeutic strategies, validating women’s experiences and concerns with rUTI while limiting unnecessary antibiotics remains our best option,” she wrote.
Dr. Scott and Dr. Van Kuiken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Time to positivity doesn’t predict mortality in bloodstream infections with enterococci
A short time to positivity (TTP), the period from incubation to blood culture positivity, may help predict mortality rates for patients with Enterococcus faecalis and vancomycin-sensitive E faecium (VSEfm) bloodstream infections (BSIs), but it is not an independent predictor of risk for death from bloodstream infections caused by enterococci, new research indicates.
Katharina Michelson, of the Institute of Microbiology, Jena University Hospital, Germany, and colleagues conducted a single-site study at Jena University Hospital that included 244 patients with monomicrobial BSIs to assess the value of TTP as a prognostic or diagnostic tool.
Death in the hospital was the primary endpoint considered in the study, which was conducted from January 2014 through December 2016. The shortest TTP of blood cultures was compared among groups.
Findings were published online in April in Diagnostic Microbiology and Infectious Disease.
Among the 244 patients with monomicrobial BSIs, 22.1% of cases were caused by E faecalis, 55.3% were caused by VSEfm, and 22.5% were caused by vancomycin-resistant E faecium (VREfm).
Average TTP of Enterococcus BSI (E-BSI) was 11.6 hours. The researchers found no significant association between risk for death and time to positivity with bloodstream infections with E faecalis, VSEfm, or VREfm, or its cutoffs.
The mortality rate of patients with bloodstream infections with E faecalis was 16.7%; for VSEfm, 26.7%; and for vancomycin-resistant E faecium, 38.2%. Cutoffs showed a significantly higher death rate when TTP was longer but were not risk factors in survival analysis.
The authors explain that “in literature, TTP has not always been proven to be a reliable parameter.”
Sam Aitken, PharmD, MPH, who is a pharmacy specialist for infectious diseases at Michigan Medicine, Ann Arbor, said in an interview that the main message from the article is that the TTP of E faecalis is quite different from that of E faecium and that “that’s in line with what we know about generally with how these organisms come about in patients.”
“This paper reinforces the differences that are sometimes underappreciated between these organisms because they are both enterococci,” he said.
The authors say appropriate antimicrobial therapy can lead to misinterpretation of TTP, so only patients who received inappropriate antimicrobial therapy on the day of positive blood culture were included in the study.
However, Dr. Aitken said that methodology doesn’t account for “immortal time bias.”
“They didn’t account for the fact that patients who tend to get active antibiotics are the ones who live longer. So unless you account for it, you’re not necessarily going to find that patients who get active antibiotics have improved survival,” he said.
The authors point out that finding new methods for quickly identifying patients with E-BSI is a high priority.
The mortality rates of E-BSI vary between 20% for E faecalis and 50% for E faecium.
Resistance to vancomycin is common in E faecium infections and is associated with high mortality, longer hospital stays, and increased costs. Vancomycin-resistant E faecium is part of a group of bacteria that is associated with multidrug resistance and nosocomial infections.
Dr. Aitken said that rather than TTP, “the best risk predictors are going to be in the microbiome studies we’re seeing. If there is a future for figuring out who’s going to get significant E faecium infections, at least, it’s going to be in the microbiome.”
Limitations of the study include its small size; the possibility of missing data, owing to the fact that the study was retrospective; potential delays to incubation; and the possibility of contamination of blood cultures.
The authors and Dr. Aitken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A short time to positivity (TTP), the period from incubation to blood culture positivity, may help predict mortality rates for patients with Enterococcus faecalis and vancomycin-sensitive E faecium (VSEfm) bloodstream infections (BSIs), but it is not an independent predictor of risk for death from bloodstream infections caused by enterococci, new research indicates.
Katharina Michelson, of the Institute of Microbiology, Jena University Hospital, Germany, and colleagues conducted a single-site study at Jena University Hospital that included 244 patients with monomicrobial BSIs to assess the value of TTP as a prognostic or diagnostic tool.
Death in the hospital was the primary endpoint considered in the study, which was conducted from January 2014 through December 2016. The shortest TTP of blood cultures was compared among groups.
Findings were published online in April in Diagnostic Microbiology and Infectious Disease.
Among the 244 patients with monomicrobial BSIs, 22.1% of cases were caused by E faecalis, 55.3% were caused by VSEfm, and 22.5% were caused by vancomycin-resistant E faecium (VREfm).
Average TTP of Enterococcus BSI (E-BSI) was 11.6 hours. The researchers found no significant association between risk for death and time to positivity with bloodstream infections with E faecalis, VSEfm, or VREfm, or its cutoffs.
The mortality rate of patients with bloodstream infections with E faecalis was 16.7%; for VSEfm, 26.7%; and for vancomycin-resistant E faecium, 38.2%. Cutoffs showed a significantly higher death rate when TTP was longer but were not risk factors in survival analysis.
The authors explain that “in literature, TTP has not always been proven to be a reliable parameter.”
Sam Aitken, PharmD, MPH, who is a pharmacy specialist for infectious diseases at Michigan Medicine, Ann Arbor, said in an interview that the main message from the article is that the TTP of E faecalis is quite different from that of E faecium and that “that’s in line with what we know about generally with how these organisms come about in patients.”
“This paper reinforces the differences that are sometimes underappreciated between these organisms because they are both enterococci,” he said.
The authors say appropriate antimicrobial therapy can lead to misinterpretation of TTP, so only patients who received inappropriate antimicrobial therapy on the day of positive blood culture were included in the study.
However, Dr. Aitken said that methodology doesn’t account for “immortal time bias.”
“They didn’t account for the fact that patients who tend to get active antibiotics are the ones who live longer. So unless you account for it, you’re not necessarily going to find that patients who get active antibiotics have improved survival,” he said.
The authors point out that finding new methods for quickly identifying patients with E-BSI is a high priority.
The mortality rates of E-BSI vary between 20% for E faecalis and 50% for E faecium.
Resistance to vancomycin is common in E faecium infections and is associated with high mortality, longer hospital stays, and increased costs. Vancomycin-resistant E faecium is part of a group of bacteria that is associated with multidrug resistance and nosocomial infections.
Dr. Aitken said that rather than TTP, “the best risk predictors are going to be in the microbiome studies we’re seeing. If there is a future for figuring out who’s going to get significant E faecium infections, at least, it’s going to be in the microbiome.”
Limitations of the study include its small size; the possibility of missing data, owing to the fact that the study was retrospective; potential delays to incubation; and the possibility of contamination of blood cultures.
The authors and Dr. Aitken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A short time to positivity (TTP), the period from incubation to blood culture positivity, may help predict mortality rates for patients with Enterococcus faecalis and vancomycin-sensitive E faecium (VSEfm) bloodstream infections (BSIs), but it is not an independent predictor of risk for death from bloodstream infections caused by enterococci, new research indicates.
Katharina Michelson, of the Institute of Microbiology, Jena University Hospital, Germany, and colleagues conducted a single-site study at Jena University Hospital that included 244 patients with monomicrobial BSIs to assess the value of TTP as a prognostic or diagnostic tool.
Death in the hospital was the primary endpoint considered in the study, which was conducted from January 2014 through December 2016. The shortest TTP of blood cultures was compared among groups.
Findings were published online in April in Diagnostic Microbiology and Infectious Disease.
Among the 244 patients with monomicrobial BSIs, 22.1% of cases were caused by E faecalis, 55.3% were caused by VSEfm, and 22.5% were caused by vancomycin-resistant E faecium (VREfm).
Average TTP of Enterococcus BSI (E-BSI) was 11.6 hours. The researchers found no significant association between risk for death and time to positivity with bloodstream infections with E faecalis, VSEfm, or VREfm, or its cutoffs.
The mortality rate of patients with bloodstream infections with E faecalis was 16.7%; for VSEfm, 26.7%; and for vancomycin-resistant E faecium, 38.2%. Cutoffs showed a significantly higher death rate when TTP was longer but were not risk factors in survival analysis.
The authors explain that “in literature, TTP has not always been proven to be a reliable parameter.”
Sam Aitken, PharmD, MPH, who is a pharmacy specialist for infectious diseases at Michigan Medicine, Ann Arbor, said in an interview that the main message from the article is that the TTP of E faecalis is quite different from that of E faecium and that “that’s in line with what we know about generally with how these organisms come about in patients.”
“This paper reinforces the differences that are sometimes underappreciated between these organisms because they are both enterococci,” he said.
The authors say appropriate antimicrobial therapy can lead to misinterpretation of TTP, so only patients who received inappropriate antimicrobial therapy on the day of positive blood culture were included in the study.
However, Dr. Aitken said that methodology doesn’t account for “immortal time bias.”
“They didn’t account for the fact that patients who tend to get active antibiotics are the ones who live longer. So unless you account for it, you’re not necessarily going to find that patients who get active antibiotics have improved survival,” he said.
The authors point out that finding new methods for quickly identifying patients with E-BSI is a high priority.
The mortality rates of E-BSI vary between 20% for E faecalis and 50% for E faecium.
Resistance to vancomycin is common in E faecium infections and is associated with high mortality, longer hospital stays, and increased costs. Vancomycin-resistant E faecium is part of a group of bacteria that is associated with multidrug resistance and nosocomial infections.
Dr. Aitken said that rather than TTP, “the best risk predictors are going to be in the microbiome studies we’re seeing. If there is a future for figuring out who’s going to get significant E faecium infections, at least, it’s going to be in the microbiome.”
Limitations of the study include its small size; the possibility of missing data, owing to the fact that the study was retrospective; potential delays to incubation; and the possibility of contamination of blood cultures.
The authors and Dr. Aitken have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Untreatable, drug-resistant fungus found in Texas and Washington, D.C.
The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.
In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.
In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.
These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.
Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.
In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.
C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.
Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.
“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.
Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.
COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.
They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”
Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.
Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”
Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.
In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.
Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”
There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.
Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.
In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.
In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.
These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.
Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.
In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.
C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.
Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.
“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.
Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.
COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.
They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”
Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.
Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”
Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.
In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.
Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”
There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.
Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.
In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.
In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.
These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.
Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.
In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.
C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.
Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.
“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.
Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.
COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.
They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”
Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.
Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”
Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.
In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.
Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”
There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.
Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Acid suppression therapy increases intestinal colonization of MDROs
Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.
Study design: Systematic review and meta-analysis.
Setting: Observational studies searched from database through July 2019.
Synopsis: A total of 26 observational studies published during 1996-2019 with 29,382 patients were included in this meta-analysis. Of those, 24 studies directly measured intestinal MDRO carriage and 2 used urinary tract infections (UTIs) as the outcome measure, since most UTIs are caused by bacteria that colonize the intestinal tract. Target MDROs included multidrug-resistant Enterobacteriaceae (MRD-E) and vancomycin-resistant enterococci (VRE). Meta-analysis demonstrated that acid suppression is associated with increased odds of intestinal MDRO colonization (MDR-E: odds ratio, 1.60; 95% confidence interval, 1.33-1.92; VRE: OR, 1.97; 95% CI, 1.49-2.60), in both community and health care settings. The risk was similar for colonization with MDR-E and VRE. Regarding the effect of acid suppression by drug class, results were mixed with some studies demonstrating increased risk of MDRO in PPI users only while others reported increased risk only with H2-receptor antagonists.
Bottom line: Acid suppression therapy is associated with increased odds of MDRO colonization. While observational studies cannot prove causation, it is wise to avoid excessive use of acid suppressants.
Citation: Willems RPJ et al. Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis. JAMA Intern Med. 2020 Feb 24;180(4):561-71.
Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.
Study design: Systematic review and meta-analysis.
Setting: Observational studies searched from database through July 2019.
Synopsis: A total of 26 observational studies published during 1996-2019 with 29,382 patients were included in this meta-analysis. Of those, 24 studies directly measured intestinal MDRO carriage and 2 used urinary tract infections (UTIs) as the outcome measure, since most UTIs are caused by bacteria that colonize the intestinal tract. Target MDROs included multidrug-resistant Enterobacteriaceae (MRD-E) and vancomycin-resistant enterococci (VRE). Meta-analysis demonstrated that acid suppression is associated with increased odds of intestinal MDRO colonization (MDR-E: odds ratio, 1.60; 95% confidence interval, 1.33-1.92; VRE: OR, 1.97; 95% CI, 1.49-2.60), in both community and health care settings. The risk was similar for colonization with MDR-E and VRE. Regarding the effect of acid suppression by drug class, results were mixed with some studies demonstrating increased risk of MDRO in PPI users only while others reported increased risk only with H2-receptor antagonists.
Bottom line: Acid suppression therapy is associated with increased odds of MDRO colonization. While observational studies cannot prove causation, it is wise to avoid excessive use of acid suppressants.
Citation: Willems RPJ et al. Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis. JAMA Intern Med. 2020 Feb 24;180(4):561-71.
Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.
Study design: Systematic review and meta-analysis.
Setting: Observational studies searched from database through July 2019.
Synopsis: A total of 26 observational studies published during 1996-2019 with 29,382 patients were included in this meta-analysis. Of those, 24 studies directly measured intestinal MDRO carriage and 2 used urinary tract infections (UTIs) as the outcome measure, since most UTIs are caused by bacteria that colonize the intestinal tract. Target MDROs included multidrug-resistant Enterobacteriaceae (MRD-E) and vancomycin-resistant enterococci (VRE). Meta-analysis demonstrated that acid suppression is associated with increased odds of intestinal MDRO colonization (MDR-E: odds ratio, 1.60; 95% confidence interval, 1.33-1.92; VRE: OR, 1.97; 95% CI, 1.49-2.60), in both community and health care settings. The risk was similar for colonization with MDR-E and VRE. Regarding the effect of acid suppression by drug class, results were mixed with some studies demonstrating increased risk of MDRO in PPI users only while others reported increased risk only with H2-receptor antagonists.
Bottom line: Acid suppression therapy is associated with increased odds of MDRO colonization. While observational studies cannot prove causation, it is wise to avoid excessive use of acid suppressants.
Citation: Willems RPJ et al. Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis. JAMA Intern Med. 2020 Feb 24;180(4):561-71.
Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.
Antimicrobial resistance threat continues during COVID-19
The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.
For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.
“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.
“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.
The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.
The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
A ‘terrifying’ personal experience
Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.
“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.
A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.
Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.
“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”
The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.
“Ultimately, I had eight surgeries in 2 weeks,” she said.
“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.
When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.
“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
Incentivizing new antimicrobial agents
A lack of new antimicrobials in development is not a new story.
“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”
One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.
Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.
Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.
“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.
Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
Everyone’s concern
AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.
“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.
Furthermore, consumers are partially to blame as well, Dr. Fowler noted.
“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.
“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
Reasons for optimism
Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.
“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.
For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.
Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.
Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.
When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
Patient outcomes
The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.
“But his life is forever changed,” he added.
Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.
“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”
A version of this article first appeared on WebMD.com.
The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.
For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.
“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.
“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.
The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.
The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
A ‘terrifying’ personal experience
Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.
“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.
A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.
Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.
“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”
The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.
“Ultimately, I had eight surgeries in 2 weeks,” she said.
“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.
When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.
“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
Incentivizing new antimicrobial agents
A lack of new antimicrobials in development is not a new story.
“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”
One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.
Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.
Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.
“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.
Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
Everyone’s concern
AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.
“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.
Furthermore, consumers are partially to blame as well, Dr. Fowler noted.
“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.
“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
Reasons for optimism
Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.
“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.
For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.
Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.
Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.
When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
Patient outcomes
The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.
“But his life is forever changed,” he added.
Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.
“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”
A version of this article first appeared on WebMD.com.
The stark realities of antimicrobial resistance – including rising rates of difficult-to-treat infections, lack of a robust pipeline of future antimicrobials, and COVID-19 treatments that leave people more vulnerable to infections – remain urgent priorities, experts say.
For some patients, the pandemic and antimicrobial resistance (AMR) are intertwined.
“One patient I’m seeing now in service really underscores how the two interact,” Vance Fowler, MD, said during a June 30 media briefing sponsored by the Infectious Diseases Society of America (IDSA). A man in his mid-40s, married with a small child, developed COVID-19 in early January 2021. He was intubated, spent about 1 month in the ICU, and managed to survive.
“But since then he has been struck with a series of progressively more drug resistant bacteria,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C., and chair of the IDSA Antimicrobial Resistance Committee.
The patient acquired Pseudomonas ventilator-associated pneumonia. Although the infection initially responded to standard antibiotics, he has experienced relapses over the past few months. Through these multiple infections the Pseudomonas grew increasingly pan-resistant to treatment.
The only remaining antimicrobial agent for this patient, Dr. Fowler said, is “a case study in what we are describing ... a drug that is used relatively infrequently, that is fairly expensive, but for that particular patient is absolutely vital.”
A ‘terrifying’ personal experience
Tori Kinamon, a Duke University medical student and Food and Drug Administration antibacterial drug resistance fellow, joined Dr. Fowler at the IDSA briefing. She shared her personal journey of surviving a methicillin-resistant Staphylococcus aureus (MRSA) infection, one that sparked her interest in becoming a physician.
“I had a very frightening and unexpected confrontation with antimicrobial resistance when I was a freshman in college,” Ms. Kinamon said.
A few days after competing in a Division One gymnastics championship, she felt a gradual onset of pain in her left hamstring. The pain grew acutely worse and, within days, her leg become red, swollen, and painful to the touch.
Ms. Kinamon was admitted to the hospital for suspected cellulitis and put on intravenous antibiotics.
“However, my clinical condition continued to decline,” she recalled. “Imaging studies revealed a 15-cm abscess deep in my hamstring.”
The limb- and life-threatening infection left her wondering if she would come out of surgery with both legs.
“Ultimately, I had eight surgeries in 2 weeks,” she said.
“As a 19-year-old collegiate athlete, that’s terrifying. And I never imagined that something like that would happen to me – until it did,” said Ms. Kinamon, who is an NCAA infection prevention advocate.
When Ms. Kinamon’s kidneys could no longer tolerate vancomycin, she was switched to daptomycin.
“I reflect quite frequently on how having that one extra drug in the stockpile had a significant impact on my outcome,” she said.
Incentivizing new antimicrobial agents
A lack of new antimicrobials in development is not a new story.
“There’s been a chill that’s been sustained on the antibiotic development field. Most large pharmaceutical companies have left the area of anti-infectants and the bulk of research and development is now in small pharmaceutical companies,” Dr. Fowler said. “And they’re struggling.”
One potential solution is the Pasteur Act, a bipartisan bill reintroduced in Congress and supported by IDSA. The bill encourages pharmaceutical companies to develop new antimicrobial agents with funding not linked to sales or use of the drugs.
Furthermore, the bill emphasizes appropriate use of these agents through effective stewardship programs.
Although some institutions shifted resources away from AMR out of necessity when COVID-19 struck, “I can say certainly from our experience at Duke that at least stewardship was alive and well. It was not relegated to the side,” Dr. Fowler said.
“In fact,” he added, “if anything, COVID really emphasized the importance of stewardship” by helping clinicians with guidance on the use of remdesivir and other antivirals during the pandemic.
Also, in some instances, treatments used to keep people with COVID-19 alive can paradoxically place them at higher risk for other infections, Dr. Fowler said, citing corticosteroids as an example.
Everyone’s concern
AMR isn’t just an issue in hospital settings, either. Ms. Kinamon reiterated that she picked up the infection in an athletic environment.
“Antimicrobial resistance is not just a problem for ICU patients in the hospital. I was the healthiest I had ever been and just very nearly escaped death due to one of these infections,” she said. ”As rates of resistance rise as these pathogens become more virulent, AMR is becoming more and more of a community threat,” she added.
Furthermore, consumers are partially to blame as well, Dr. Fowler noted.
“It’s interesting when you look at the surveys of the numbers of patients that have used someone else’s antibiotics” or leftover antimicrobial agents from a prior infection.
“It’s really startling ... that’s the sort of antibiotic overuse that directly contributes to antibacterial resistance,” he said.
Reasons for optimism
Promising advances in diagnostics, treatment, and prevention of AMRs are underway, Dr. Fowler said.
“It always gets me really excited to talk about it. It’s amazing what technology and scientific discovery can bring to this discussion and to this threat,” he said.
For example, there is a “silent revolution” in diagnostics with the aim to rapidly provide life-saving actionable data on a real patient in nearly real time.
Traditionally, “you start off by treating what should be there” while awaiting results of tests to narrow down therapy, Dr. Fowler said. However, a whole host of new platforms are in development to reduce the time to susceptibility results. This kind of technology has “the potential to transform our ability to take care of patients, giving them the right drug at the right time and no more,” he said.
Another promising avenue of research involves bacteriophages. Dr. Fowler is principal investigator on a clinical trial underway to evaluate bacteriophages as adjunct therapy for MRSA bacteremia.
When it comes to prevention on AMR infections in the future, “I continue to be optimistic about the possibility of vaccines to prevent many of these infections,” Dr. Fowler said, adding that companies are working on vaccines against these kinds of infections caused by MRSA or Escherichia coli, for example.
Patient outcomes
The man in his 40s with the multidrug resistant Pseudomonas infections “is now to the point where he’s walking in the halls and I think he’ll get out of the hospital eventually,” Dr. Fowler said.
“But his life is forever changed,” he added.
Ms. Kinamon’s recovery from MRSA included time in the ICU, 1 month in a regular hospital setting, and 5 months at home.
“It sparked my interest in antibiotic research and development because I see myself as a direct beneficiary of the stockpile of antibiotics that were available to treat my infection,” Ms. Kinamon said. “Now as a medical student working with patients who have similar infections, I feel a deep empathy and connectedness to them because they ask the same questions that I did.”
A version of this article first appeared on WebMD.com.
Ear tubes no better than antibiotics for otitis media in young kids
The debate over tympanostomy tubes versus antibiotics for recurrent acute otitis media (AOM) in young children is long-standing. Now, results of a randomized controlled trial show that tubes do not significantly lower the rate of episodes, compared with antibiotics, and medical management doesn’t increase antibiotic resistance.
“We found no evidence of microbial resistance from treating with antibiotics. If there’s not an impact on resistance, why take unnecessary chances on complications of surgery?” lead author Alejandro Hoberman, MD, from Children’s Hospital of Pittsburgh, said in an interview.
The study by Dr. Hoberman and colleagues was published May 13 in the New England Journal of Medicine.
AOM is the most frequent condition diagnosed in children in the United States after the common cold, affecting five of six children younger than 3 years. It is the leading indication for antimicrobial treatment, and tympanostomy tube insertion is the most frequently performed pediatric operation after the newborn period.
Randomized controlled clinical trials were conducted in the 1980s, but by the 1990s, questions of overuse arose. The American Academy of Otolaryngology–Head and Neck Surgery Foundation published the first clinical practice guidelines in 2013.
Parents must weigh the pros and cons. The use of tubes may avoid or delay the next round of drugs, but tubes cost more and introduce small risks (anesthesia, refractory otorrhea, tube blockage, premature dislocation or extrusion, and mild conductive hearing loss).
“We addressed issues that plagued older studies – a longer-term follow-up of 2 years, validated diagnoses of infection to determine eligibility – and used rating scales to measure quality of life,” Dr. Hoberman said.
The researchers randomly assigned children to receive antibiotics or tubes. To be eligible, children had to be 6-35 months of age and have had at least three episodes of AOM within 6 months or at least four episodes within 12 months, including at least one within the preceding 6 months.
The primary outcome was the mean number of episodes of AOM per child-year. Children were assessed at 8-week intervals and within 48 hours of developing symptoms of ear infection. The medically treated children received oral amoxicillin or, if that was ineffective, intramuscular ceftriaxone.
Criteria for determining treatment failure included persistent otorrhea, tympanic membrane perforation, antibiotic-associated diarrhea, reaction to anesthesia, and recurrence of AOM at a frequency equal to the frequency before antibiotic treatment.
In comparing tympanostomy tubes with antibiotics, Dr. Hoberman said, “We were unable to show benefit in the rate of ear infections per child per year over a 2-year period.” As expected, the infection rate fell by about half from the first year to the second in all children.
Overall, the investigators found “no substantial differences between treatment groups” with regard to AOM frequency, percentage of severe episodes, extent of antimicrobial resistance, quality of life for the children, and parental stress.
In an intention-to-treat analysis, the rate of AOM episodes per child-year during the study was 1.48 ± 0.08 for tubes and 1.56 ± 0.08 for antibiotics (P = .66).
However, randomization was not maintained in the intention-to-treat arm. Ten percent (13 of 129) of the children slated to receive tubes didn’t get them because of parental request. Conversely, 16% (54 of 121) of children in the antibiotic group received tubes, 35 (29%) of them in accordance with the trial protocol because of frequent recurrences, and 19 (16%) at parental request.
In a per-protocol analysis, rates of AOM episodes per child-year were 1.47 ± 0.08 for tubes and 1.72 ± 0.11 for antibiotics.
Tubes were associated with longer time until the first ear infection post placement, at a median of 4.34 months, compared with 2.33 months for children who received antibiotics. A smaller percentage of children in the tube group had treatment failure than in the antibiotic group (45% vs. 62%). Children who received tubes also had fewer days per year with symptoms in comparison with the children in the antibiotic group (mean, 2.00 ± 0.29 days vs. 8.33 ± 0.59 days).
The frequency distribution of AOM episodes, the percentage of severe episodes, and antimicrobial resistance detected in respiratory specimens were the same for both groups.
“Hoberman and colleagues add to our knowledge of managing children with recurrent ear infections with a large and rigorous clinical trial showing comparable efficacy of tympanostomy tube insertion, with antibiotic eardrops for new infections versus watchful waiting, with intermittent oral antibiotics, if further ear infections occur,” said Richard M. Rosenfeld, MD, MPH, MBA, distinguished professor and chairman, department of otolaryngology, SUNY Downstate Medical Center, New York.
However, in an accompanying editorial, Ellen R. Wald, MD, from the University of Wisconsin, Madison, pointed out that the sample size was smaller than desired, owing to participants switching groups.
In addition, Dr. Rosenfeld, who was the lead author of the 2013 guidelines, said the study likely underestimates the impact of tubes “because about two-thirds of the children who received them did not have persistent middle-ear fluid at baseline and would not have been candidates for tubes based on the current national guideline on tube indications.”
“Both tubes and intermittent antibiotic therapy are effective for managing recurrent AOM, and parents of children with persistent middle-ear effusion should engage in shared decision-making with their physician to decide on the best management option,” said Dr. Rosenfeld. “When in doubt, watchful waiting is appropriate because many children with recurrent AOM do better over time.”
Dr. Hoberman owns stock in Kaizen Bioscience and holds patents on devices to diagnose and treat AOM. One coauthor consults for Merck. Dr. Wald and Dr. Rosenfeld report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate over tympanostomy tubes versus antibiotics for recurrent acute otitis media (AOM) in young children is long-standing. Now, results of a randomized controlled trial show that tubes do not significantly lower the rate of episodes, compared with antibiotics, and medical management doesn’t increase antibiotic resistance.
“We found no evidence of microbial resistance from treating with antibiotics. If there’s not an impact on resistance, why take unnecessary chances on complications of surgery?” lead author Alejandro Hoberman, MD, from Children’s Hospital of Pittsburgh, said in an interview.
The study by Dr. Hoberman and colleagues was published May 13 in the New England Journal of Medicine.
AOM is the most frequent condition diagnosed in children in the United States after the common cold, affecting five of six children younger than 3 years. It is the leading indication for antimicrobial treatment, and tympanostomy tube insertion is the most frequently performed pediatric operation after the newborn period.
Randomized controlled clinical trials were conducted in the 1980s, but by the 1990s, questions of overuse arose. The American Academy of Otolaryngology–Head and Neck Surgery Foundation published the first clinical practice guidelines in 2013.
Parents must weigh the pros and cons. The use of tubes may avoid or delay the next round of drugs, but tubes cost more and introduce small risks (anesthesia, refractory otorrhea, tube blockage, premature dislocation or extrusion, and mild conductive hearing loss).
“We addressed issues that plagued older studies – a longer-term follow-up of 2 years, validated diagnoses of infection to determine eligibility – and used rating scales to measure quality of life,” Dr. Hoberman said.
The researchers randomly assigned children to receive antibiotics or tubes. To be eligible, children had to be 6-35 months of age and have had at least three episodes of AOM within 6 months or at least four episodes within 12 months, including at least one within the preceding 6 months.
The primary outcome was the mean number of episodes of AOM per child-year. Children were assessed at 8-week intervals and within 48 hours of developing symptoms of ear infection. The medically treated children received oral amoxicillin or, if that was ineffective, intramuscular ceftriaxone.
Criteria for determining treatment failure included persistent otorrhea, tympanic membrane perforation, antibiotic-associated diarrhea, reaction to anesthesia, and recurrence of AOM at a frequency equal to the frequency before antibiotic treatment.
In comparing tympanostomy tubes with antibiotics, Dr. Hoberman said, “We were unable to show benefit in the rate of ear infections per child per year over a 2-year period.” As expected, the infection rate fell by about half from the first year to the second in all children.
Overall, the investigators found “no substantial differences between treatment groups” with regard to AOM frequency, percentage of severe episodes, extent of antimicrobial resistance, quality of life for the children, and parental stress.
In an intention-to-treat analysis, the rate of AOM episodes per child-year during the study was 1.48 ± 0.08 for tubes and 1.56 ± 0.08 for antibiotics (P = .66).
However, randomization was not maintained in the intention-to-treat arm. Ten percent (13 of 129) of the children slated to receive tubes didn’t get them because of parental request. Conversely, 16% (54 of 121) of children in the antibiotic group received tubes, 35 (29%) of them in accordance with the trial protocol because of frequent recurrences, and 19 (16%) at parental request.
In a per-protocol analysis, rates of AOM episodes per child-year were 1.47 ± 0.08 for tubes and 1.72 ± 0.11 for antibiotics.
Tubes were associated with longer time until the first ear infection post placement, at a median of 4.34 months, compared with 2.33 months for children who received antibiotics. A smaller percentage of children in the tube group had treatment failure than in the antibiotic group (45% vs. 62%). Children who received tubes also had fewer days per year with symptoms in comparison with the children in the antibiotic group (mean, 2.00 ± 0.29 days vs. 8.33 ± 0.59 days).
The frequency distribution of AOM episodes, the percentage of severe episodes, and antimicrobial resistance detected in respiratory specimens were the same for both groups.
“Hoberman and colleagues add to our knowledge of managing children with recurrent ear infections with a large and rigorous clinical trial showing comparable efficacy of tympanostomy tube insertion, with antibiotic eardrops for new infections versus watchful waiting, with intermittent oral antibiotics, if further ear infections occur,” said Richard M. Rosenfeld, MD, MPH, MBA, distinguished professor and chairman, department of otolaryngology, SUNY Downstate Medical Center, New York.
However, in an accompanying editorial, Ellen R. Wald, MD, from the University of Wisconsin, Madison, pointed out that the sample size was smaller than desired, owing to participants switching groups.
In addition, Dr. Rosenfeld, who was the lead author of the 2013 guidelines, said the study likely underestimates the impact of tubes “because about two-thirds of the children who received them did not have persistent middle-ear fluid at baseline and would not have been candidates for tubes based on the current national guideline on tube indications.”
“Both tubes and intermittent antibiotic therapy are effective for managing recurrent AOM, and parents of children with persistent middle-ear effusion should engage in shared decision-making with their physician to decide on the best management option,” said Dr. Rosenfeld. “When in doubt, watchful waiting is appropriate because many children with recurrent AOM do better over time.”
Dr. Hoberman owns stock in Kaizen Bioscience and holds patents on devices to diagnose and treat AOM. One coauthor consults for Merck. Dr. Wald and Dr. Rosenfeld report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The debate over tympanostomy tubes versus antibiotics for recurrent acute otitis media (AOM) in young children is long-standing. Now, results of a randomized controlled trial show that tubes do not significantly lower the rate of episodes, compared with antibiotics, and medical management doesn’t increase antibiotic resistance.
“We found no evidence of microbial resistance from treating with antibiotics. If there’s not an impact on resistance, why take unnecessary chances on complications of surgery?” lead author Alejandro Hoberman, MD, from Children’s Hospital of Pittsburgh, said in an interview.
The study by Dr. Hoberman and colleagues was published May 13 in the New England Journal of Medicine.
AOM is the most frequent condition diagnosed in children in the United States after the common cold, affecting five of six children younger than 3 years. It is the leading indication for antimicrobial treatment, and tympanostomy tube insertion is the most frequently performed pediatric operation after the newborn period.
Randomized controlled clinical trials were conducted in the 1980s, but by the 1990s, questions of overuse arose. The American Academy of Otolaryngology–Head and Neck Surgery Foundation published the first clinical practice guidelines in 2013.
Parents must weigh the pros and cons. The use of tubes may avoid or delay the next round of drugs, but tubes cost more and introduce small risks (anesthesia, refractory otorrhea, tube blockage, premature dislocation or extrusion, and mild conductive hearing loss).
“We addressed issues that plagued older studies – a longer-term follow-up of 2 years, validated diagnoses of infection to determine eligibility – and used rating scales to measure quality of life,” Dr. Hoberman said.
The researchers randomly assigned children to receive antibiotics or tubes. To be eligible, children had to be 6-35 months of age and have had at least three episodes of AOM within 6 months or at least four episodes within 12 months, including at least one within the preceding 6 months.
The primary outcome was the mean number of episodes of AOM per child-year. Children were assessed at 8-week intervals and within 48 hours of developing symptoms of ear infection. The medically treated children received oral amoxicillin or, if that was ineffective, intramuscular ceftriaxone.
Criteria for determining treatment failure included persistent otorrhea, tympanic membrane perforation, antibiotic-associated diarrhea, reaction to anesthesia, and recurrence of AOM at a frequency equal to the frequency before antibiotic treatment.
In comparing tympanostomy tubes with antibiotics, Dr. Hoberman said, “We were unable to show benefit in the rate of ear infections per child per year over a 2-year period.” As expected, the infection rate fell by about half from the first year to the second in all children.
Overall, the investigators found “no substantial differences between treatment groups” with regard to AOM frequency, percentage of severe episodes, extent of antimicrobial resistance, quality of life for the children, and parental stress.
In an intention-to-treat analysis, the rate of AOM episodes per child-year during the study was 1.48 ± 0.08 for tubes and 1.56 ± 0.08 for antibiotics (P = .66).
However, randomization was not maintained in the intention-to-treat arm. Ten percent (13 of 129) of the children slated to receive tubes didn’t get them because of parental request. Conversely, 16% (54 of 121) of children in the antibiotic group received tubes, 35 (29%) of them in accordance with the trial protocol because of frequent recurrences, and 19 (16%) at parental request.
In a per-protocol analysis, rates of AOM episodes per child-year were 1.47 ± 0.08 for tubes and 1.72 ± 0.11 for antibiotics.
Tubes were associated with longer time until the first ear infection post placement, at a median of 4.34 months, compared with 2.33 months for children who received antibiotics. A smaller percentage of children in the tube group had treatment failure than in the antibiotic group (45% vs. 62%). Children who received tubes also had fewer days per year with symptoms in comparison with the children in the antibiotic group (mean, 2.00 ± 0.29 days vs. 8.33 ± 0.59 days).
The frequency distribution of AOM episodes, the percentage of severe episodes, and antimicrobial resistance detected in respiratory specimens were the same for both groups.
“Hoberman and colleagues add to our knowledge of managing children with recurrent ear infections with a large and rigorous clinical trial showing comparable efficacy of tympanostomy tube insertion, with antibiotic eardrops for new infections versus watchful waiting, with intermittent oral antibiotics, if further ear infections occur,” said Richard M. Rosenfeld, MD, MPH, MBA, distinguished professor and chairman, department of otolaryngology, SUNY Downstate Medical Center, New York.
However, in an accompanying editorial, Ellen R. Wald, MD, from the University of Wisconsin, Madison, pointed out that the sample size was smaller than desired, owing to participants switching groups.
In addition, Dr. Rosenfeld, who was the lead author of the 2013 guidelines, said the study likely underestimates the impact of tubes “because about two-thirds of the children who received them did not have persistent middle-ear fluid at baseline and would not have been candidates for tubes based on the current national guideline on tube indications.”
“Both tubes and intermittent antibiotic therapy are effective for managing recurrent AOM, and parents of children with persistent middle-ear effusion should engage in shared decision-making with their physician to decide on the best management option,” said Dr. Rosenfeld. “When in doubt, watchful waiting is appropriate because many children with recurrent AOM do better over time.”
Dr. Hoberman owns stock in Kaizen Bioscience and holds patents on devices to diagnose and treat AOM. One coauthor consults for Merck. Dr. Wald and Dr. Rosenfeld report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Low-risk preterm infants may not need antibiotics
Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.
Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.
However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.
Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.
To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.
The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).
Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.
However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
Further risk factor identification could curb antibiotic use
In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.
Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.
However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.
Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.
To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.
The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).
Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.
However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
Further risk factor identification could curb antibiotic use
In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
Selective use of antibiotics based on birth circumstances may reduce unnecessary antibiotic exposure for preterm infants at risk of early-onset sepsis, based on data from 340 preterm infants at a single center.
Preterm infants born because of preterm labor, premature rupture of membranes, and/or intraamniotic infection (IAI) are considered at increased risk for early-onset sepsis, and current management strategies include a blood culture and initiation of empirical antibiotics, said Kirtan Patel, MD, of Texas A&M University, Dallas, and colleagues in a poster (# 1720) presented at the Pediatric Academic Societies annual meeting.
However, this blanket approach “may increase the unnecessary early antibiotic exposure in preterm infants possibly leading to future adverse health outcomes,” and physicians are advised to review the risks and benefits, Dr. Patel said.
Data from previous studies suggest that preterm infants born as a result of preterm labor and/or premature rupture of membranes with adequate Group B Streptococcus (GBS) intrapartum antibiotic prophylaxis and no indication of IAI may be managed without empiric antibiotics because the early-onset sepsis risk in these infants is much lower than the ones born through IAI and inadequate GBS intrapartum antibiotic prophylaxis.
To better identify preterm birth circumstances in which antibiotics might be avoided, the researchers conducted a retrospective cohort study of preterm infants born at 28-34 weeks’ gestation during the period from Jan. 1, 2015, to Dec. 31, 2018. These infants were in the low-risk category of preterm birth because of preterm labor or premature rupture of membranes, with no IAI and adequate GBS intrapartum antibiotic prophylaxis, and no signs of cardiovascular or respiratory instability after birth. Of these, 157 (46.2%) received empiric antibiotics soon after birth and 183 infants (53.8%) did not receive empiric antibiotics.
The mean gestational age and birth weight were significantly lower in the empiric antibiotic group, but after correcting for these variables, the factors with the greatest influence on the initiation of antibiotics were maternal intrapartum antibiotic prophylaxis (odds ratio, 3.13); premature rupture of membranes (OR, 3.75); use of continuous positive airway pressure (CPAP) in the delivery room (OR, 1.84); CPAP on admission to the neonatal intensive care unit (OR, 1.94); drawing a blood culture (OR, 13.72); and a complete blood count with immature to total neutrophil ratio greater than 0.2 (OR, 3.84).
Three infants (2%) in the antibiotics group had culture-positive early-onset sepsis with Escherichia coli, compared with no infants in the no-antibiotics group. No differences in short-term hospital outcomes appeared between the two groups. The study was limited in part by the retrospective design and sample size, the researchers noted.
However, the results support a selective approach to antibiotics for preterm infants, taking various birth circumstances into account, they said.
Further risk factor identification could curb antibiotic use
In this study, empiric antibiotics were cast as a wide net to avoid missing serious infections in a few patients, said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“It is interesting in this retrospective review of 340 preterm infants that the three newborns that did have serious bacterial infection were correctly given empiric antibiotics from the start,” Dr. Joos noted. “The authors were very effective at elucidating the possible factors that go into starting or not starting empiric antibiotics, although there may be other factors in the clinician’s judgment that are being missed. … More studies are needed on this topic,” Dr. Joos said. “Further research examining how the septic newborns differ from the nonseptic ones could help to even further narrow the use of empiric antibiotics,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
FROM PAS 2021
Smart prescribing strategies improve antibiotic stewardship
“Antibiotic stewardship is never easy, and sometimes it is very difficult to differentiate what is going on with a patient in the clinical setting,” said Valerie M. Vaughn, MD, of the University of Utah, Salt Lake City, at SHM Converge, the annual conference of the Society of Hospital Medicine.
“We know from studies that 20% of hospitalized patients who receive an antibiotic have an adverse drug event from that antibiotic within 30 days,” said Dr. Vaughn.
Dr. Vaughn identified several practical ways in which hospitalists can reduce antibiotic overuse, including in the management of patients hospitalized with COVID-19.
Identify asymptomatic bacteriuria
One key area in which hospitalists can improve antibiotic stewardship is in recognizing asymptomatic bacteriuria and the harms associated with treatment, Dr. Vaughn said. For example, a common scenario for hospitalists might involve and 80-year-old woman with dementia, who can provide little in the way of history, and whose chest x-ray can’t rule out an underlying infection. This patient might have a positive urine culture, but no other signs of a urinary tract infection. “We know that asymptomatic bacteriuria is very common in hospitalized patients,” especially elderly women living in nursing home settings, she noted.
In cases of asymptomatic bacteriuria, data show that antibiotic treatment does not improve outcomes, and in fact may increase the risk of subsequent UTI, said Dr. Vaughn. Elderly patients also are at increased risk for developing antibiotic-related adverse events, especially Clostridioides difficile. Asymptomatic bacteriuria is any bacteria in the urine in the absence of signs or symptoms of a UTI, even if lab tests show pyuria, nitrates, and resistant bacteria. These lab results are often associated with inappropriate antibiotic use. “The laboratory tests can’t distinguish between asymptomatic bacteriuria and a UTI, only the symptoms can,” she emphasized.
Contain treatment of community-acquired pneumonia
Another practical point for reducing antibiotics in the hospital setting is to limit treatment of community-acquired pneumonia (CAP) to 5 days when possible. Duration matters because for many diseases, shorter durations of antibiotic treatments are just as effective as longer durations based on the latest evidence. “This is a change in dogma,” from previous thinking that patients must complete a full course, and that anything less might promote antibiotic resistance, she said.
“In fact, longer antibiotic durations kill off more healthy, normal flora, select for resistant pathogens, increase the risk of C. difficile, and increase the risk of side effects,” she said.
Ultimately, the right treatment duration for pneumonia depends on several factors including patient factors, disease, clinical stability, and rate of improvement. However, a good rule of thumb is that approximately 89% of CAP patients need only 5 days of antibiotics as long as they are afebrile for 48 hours and have 1 or fewer vital sign abnormalities by day 5 of treatment. “We do need to prescribe longer durations for patients with complications,” she emphasized.
Revisit need for antibiotics at discharge
Hospitalists also can practice antibiotic stewardship by considering four points at patient discharge, said Dr. Vaughn.
First, consider whether antibiotics can be stopped. For example, antibiotics are not needed on discharge if infection is no longer the most likely diagnosis, or if the course of antibiotics has been completed, as is often the case for patients hospitalized with CAP, she noted.
Second, if the antibiotics can’t be stopped at the time of discharge, consider whether the preferred agent is being used. Third, be sure the patient is receiving the minimum duration of antibiotics, and fourth, be sure that the dose, indication, and total planned duration with start and stop dates is written in the discharge summary, said Dr. Vaughn. “This helps with communication to our outpatient providers as well as with education to the patients themselves.”
Bacterial coinfections rare in COVID-19
Dr. Vaughn concluded the session with data from a study she conducted with colleagues on the use of empiric antibacterial therapy and community-onset bacterial coinfection in hospitalized COVID-19 patients. The study included 1,667 patients at 32 hospitals in Michigan. The number of patients treated with antibiotics varied widely among hospitals, from 30% to as much as 90%, Dr. Vaughn said.
“What we found was that more than half of hospitalized patients with COVID (57%) received empiric antibiotic therapy in the first few days of hospitalization,” she said.
However, “despite all the antibiotic use, community-onset bacterial coinfections were rare,” and occurred in only 3.5% of the patients, meaning that the number needed to treat with antibiotics to prevent a single case was about 20.
Predictors of community-onset co-infections in the patients included older age, more severe disease, patients coming from nursing homes, and those with lower BMI or kidney disease, said Dr. Vaughn. She and her team also found that procalcitonin’s positive predictive value was 9.3%, but the negative predictive value was 98.3%, so these patients were extremely likely to have no coinfection.
Dr. Vaughn said that in her practice she might order procalcitonin when considering stopping antibiotics in a patient with COVID-19 and make a decision based on the negative predictive value, but she emphasized that she does not use it in the converse situation to rely on a positive value when deciding whether to start antibiotics in these patients.
Dr. Vaughn had no financial conflicts to disclose.
“Antibiotic stewardship is never easy, and sometimes it is very difficult to differentiate what is going on with a patient in the clinical setting,” said Valerie M. Vaughn, MD, of the University of Utah, Salt Lake City, at SHM Converge, the annual conference of the Society of Hospital Medicine.
“We know from studies that 20% of hospitalized patients who receive an antibiotic have an adverse drug event from that antibiotic within 30 days,” said Dr. Vaughn.
Dr. Vaughn identified several practical ways in which hospitalists can reduce antibiotic overuse, including in the management of patients hospitalized with COVID-19.
Identify asymptomatic bacteriuria
One key area in which hospitalists can improve antibiotic stewardship is in recognizing asymptomatic bacteriuria and the harms associated with treatment, Dr. Vaughn said. For example, a common scenario for hospitalists might involve and 80-year-old woman with dementia, who can provide little in the way of history, and whose chest x-ray can’t rule out an underlying infection. This patient might have a positive urine culture, but no other signs of a urinary tract infection. “We know that asymptomatic bacteriuria is very common in hospitalized patients,” especially elderly women living in nursing home settings, she noted.
In cases of asymptomatic bacteriuria, data show that antibiotic treatment does not improve outcomes, and in fact may increase the risk of subsequent UTI, said Dr. Vaughn. Elderly patients also are at increased risk for developing antibiotic-related adverse events, especially Clostridioides difficile. Asymptomatic bacteriuria is any bacteria in the urine in the absence of signs or symptoms of a UTI, even if lab tests show pyuria, nitrates, and resistant bacteria. These lab results are often associated with inappropriate antibiotic use. “The laboratory tests can’t distinguish between asymptomatic bacteriuria and a UTI, only the symptoms can,” she emphasized.
Contain treatment of community-acquired pneumonia
Another practical point for reducing antibiotics in the hospital setting is to limit treatment of community-acquired pneumonia (CAP) to 5 days when possible. Duration matters because for many diseases, shorter durations of antibiotic treatments are just as effective as longer durations based on the latest evidence. “This is a change in dogma,” from previous thinking that patients must complete a full course, and that anything less might promote antibiotic resistance, she said.
“In fact, longer antibiotic durations kill off more healthy, normal flora, select for resistant pathogens, increase the risk of C. difficile, and increase the risk of side effects,” she said.
Ultimately, the right treatment duration for pneumonia depends on several factors including patient factors, disease, clinical stability, and rate of improvement. However, a good rule of thumb is that approximately 89% of CAP patients need only 5 days of antibiotics as long as they are afebrile for 48 hours and have 1 or fewer vital sign abnormalities by day 5 of treatment. “We do need to prescribe longer durations for patients with complications,” she emphasized.
Revisit need for antibiotics at discharge
Hospitalists also can practice antibiotic stewardship by considering four points at patient discharge, said Dr. Vaughn.
First, consider whether antibiotics can be stopped. For example, antibiotics are not needed on discharge if infection is no longer the most likely diagnosis, or if the course of antibiotics has been completed, as is often the case for patients hospitalized with CAP, she noted.
Second, if the antibiotics can’t be stopped at the time of discharge, consider whether the preferred agent is being used. Third, be sure the patient is receiving the minimum duration of antibiotics, and fourth, be sure that the dose, indication, and total planned duration with start and stop dates is written in the discharge summary, said Dr. Vaughn. “This helps with communication to our outpatient providers as well as with education to the patients themselves.”
Bacterial coinfections rare in COVID-19
Dr. Vaughn concluded the session with data from a study she conducted with colleagues on the use of empiric antibacterial therapy and community-onset bacterial coinfection in hospitalized COVID-19 patients. The study included 1,667 patients at 32 hospitals in Michigan. The number of patients treated with antibiotics varied widely among hospitals, from 30% to as much as 90%, Dr. Vaughn said.
“What we found was that more than half of hospitalized patients with COVID (57%) received empiric antibiotic therapy in the first few days of hospitalization,” she said.
However, “despite all the antibiotic use, community-onset bacterial coinfections were rare,” and occurred in only 3.5% of the patients, meaning that the number needed to treat with antibiotics to prevent a single case was about 20.
Predictors of community-onset co-infections in the patients included older age, more severe disease, patients coming from nursing homes, and those with lower BMI or kidney disease, said Dr. Vaughn. She and her team also found that procalcitonin’s positive predictive value was 9.3%, but the negative predictive value was 98.3%, so these patients were extremely likely to have no coinfection.
Dr. Vaughn said that in her practice she might order procalcitonin when considering stopping antibiotics in a patient with COVID-19 and make a decision based on the negative predictive value, but she emphasized that she does not use it in the converse situation to rely on a positive value when deciding whether to start antibiotics in these patients.
Dr. Vaughn had no financial conflicts to disclose.
“Antibiotic stewardship is never easy, and sometimes it is very difficult to differentiate what is going on with a patient in the clinical setting,” said Valerie M. Vaughn, MD, of the University of Utah, Salt Lake City, at SHM Converge, the annual conference of the Society of Hospital Medicine.
“We know from studies that 20% of hospitalized patients who receive an antibiotic have an adverse drug event from that antibiotic within 30 days,” said Dr. Vaughn.
Dr. Vaughn identified several practical ways in which hospitalists can reduce antibiotic overuse, including in the management of patients hospitalized with COVID-19.
Identify asymptomatic bacteriuria
One key area in which hospitalists can improve antibiotic stewardship is in recognizing asymptomatic bacteriuria and the harms associated with treatment, Dr. Vaughn said. For example, a common scenario for hospitalists might involve and 80-year-old woman with dementia, who can provide little in the way of history, and whose chest x-ray can’t rule out an underlying infection. This patient might have a positive urine culture, but no other signs of a urinary tract infection. “We know that asymptomatic bacteriuria is very common in hospitalized patients,” especially elderly women living in nursing home settings, she noted.
In cases of asymptomatic bacteriuria, data show that antibiotic treatment does not improve outcomes, and in fact may increase the risk of subsequent UTI, said Dr. Vaughn. Elderly patients also are at increased risk for developing antibiotic-related adverse events, especially Clostridioides difficile. Asymptomatic bacteriuria is any bacteria in the urine in the absence of signs or symptoms of a UTI, even if lab tests show pyuria, nitrates, and resistant bacteria. These lab results are often associated with inappropriate antibiotic use. “The laboratory tests can’t distinguish between asymptomatic bacteriuria and a UTI, only the symptoms can,” she emphasized.
Contain treatment of community-acquired pneumonia
Another practical point for reducing antibiotics in the hospital setting is to limit treatment of community-acquired pneumonia (CAP) to 5 days when possible. Duration matters because for many diseases, shorter durations of antibiotic treatments are just as effective as longer durations based on the latest evidence. “This is a change in dogma,” from previous thinking that patients must complete a full course, and that anything less might promote antibiotic resistance, she said.
“In fact, longer antibiotic durations kill off more healthy, normal flora, select for resistant pathogens, increase the risk of C. difficile, and increase the risk of side effects,” she said.
Ultimately, the right treatment duration for pneumonia depends on several factors including patient factors, disease, clinical stability, and rate of improvement. However, a good rule of thumb is that approximately 89% of CAP patients need only 5 days of antibiotics as long as they are afebrile for 48 hours and have 1 or fewer vital sign abnormalities by day 5 of treatment. “We do need to prescribe longer durations for patients with complications,” she emphasized.
Revisit need for antibiotics at discharge
Hospitalists also can practice antibiotic stewardship by considering four points at patient discharge, said Dr. Vaughn.
First, consider whether antibiotics can be stopped. For example, antibiotics are not needed on discharge if infection is no longer the most likely diagnosis, or if the course of antibiotics has been completed, as is often the case for patients hospitalized with CAP, she noted.
Second, if the antibiotics can’t be stopped at the time of discharge, consider whether the preferred agent is being used. Third, be sure the patient is receiving the minimum duration of antibiotics, and fourth, be sure that the dose, indication, and total planned duration with start and stop dates is written in the discharge summary, said Dr. Vaughn. “This helps with communication to our outpatient providers as well as with education to the patients themselves.”
Bacterial coinfections rare in COVID-19
Dr. Vaughn concluded the session with data from a study she conducted with colleagues on the use of empiric antibacterial therapy and community-onset bacterial coinfection in hospitalized COVID-19 patients. The study included 1,667 patients at 32 hospitals in Michigan. The number of patients treated with antibiotics varied widely among hospitals, from 30% to as much as 90%, Dr. Vaughn said.
“What we found was that more than half of hospitalized patients with COVID (57%) received empiric antibiotic therapy in the first few days of hospitalization,” she said.
However, “despite all the antibiotic use, community-onset bacterial coinfections were rare,” and occurred in only 3.5% of the patients, meaning that the number needed to treat with antibiotics to prevent a single case was about 20.
Predictors of community-onset co-infections in the patients included older age, more severe disease, patients coming from nursing homes, and those with lower BMI or kidney disease, said Dr. Vaughn. She and her team also found that procalcitonin’s positive predictive value was 9.3%, but the negative predictive value was 98.3%, so these patients were extremely likely to have no coinfection.
Dr. Vaughn said that in her practice she might order procalcitonin when considering stopping antibiotics in a patient with COVID-19 and make a decision based on the negative predictive value, but she emphasized that she does not use it in the converse situation to rely on a positive value when deciding whether to start antibiotics in these patients.
Dr. Vaughn had no financial conflicts to disclose.
FROM SHM CONVERGE 2021
Keep antibiotics unchanged in breakthrough UTIs
Changing the continuous antibiotic prophylactic agent had no significant effect on the risk of a second infection in children with breakthrough urinary tract infections (UTIs), based on data from 62 children treated at a single center.
Continuous antibiotic prophylaxis (CAP) is often used for UTI prevention in children with febrile UTIs or anomalies that predispose them to UTIs, such as vesicoureteral reflux (VUR) or bladder and bowel dysfunction, said Lane M. Shish, MPH, of the University of Washington, Bothell, and colleagues in a poster (#1245) presented at the Pediatric Academic Societies annual meeting.
CAP, once initiated, is used until a planned endpoint or a breakthrough UTI, at which point alternative treatments usually include surgical intervention or a CAP agent change, the researchers said. However, changing the CAP agent is based on consensus without evidence of benefit, they noted.
To evaluate the potential effect of switching or maintaining CAP in cases of breakthrough UTIs, the researchers conducted a retrospective cohort study of all patients younger than 18 years on CAP for UTI prevention enrolled in a pediatric urology registry between January 2013 and August 2020.
All patients experienced a breakthrough UTI while on CAP; CAP was changed for 24 patients and left unchanged for 38 patients.
The primary outcome of second-breakthrough infections occurred in 12 of the changed CAP group and 22 of the unchanged group, with a relative risk of 0.86. The percentage of second breakthrough UTIs resistant to the current CAP was not significantly different between the changed and unchanged CAP groups (75% vs. 77%; P = 0.88).
The researchers also identified a rate ratio of 0.67 for a second breakthrough UTI in the changed CAP group, and found that approximately one-third of these patients (33.3%) developed antibiotic resistance to their initial antibiotic agent and the changed antibiotic agent.
The study findings were limited by several factors, including the retrospective design and small sample size, the researchers noted.
However, the results suggest that changing the CAP after an initial breakthrough UTI in children did not increase the risk of a second breakthrough UTI, and that CAP changing did introduce a risk of developing a second UTI with increased CAP resistance, the researchers noted. The results support leaving a child’s CAP unchanged after an initial breakthrough UTI, although additional research is needed to verify the findings, including studies involving a larger cohort with a multi-institutional prospective evaluation, they concluded.
Manage UTIs to reduce recurrence and resistance
“As we know, avoiding recurrent UTIs is important in preserving renal function in pediatric patients,” said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Avoiding recurrent UTIs is also important to avoid the development and spread of multidrug-resistant organisms,” he said.
Dr. Joos said he was surprised by some of the study findings. “I was surprised that, over the course of this 7-year retrospective review, overall only approximately 50% of patients with a first breakthrough UTI on CAP developed a second breakthrough UTI,” he noted. “Also, the relative risk of a second UTI was not significantly affected by whether the CAP antibiotic was changed after the first infection,” he said. “It would be interesting to see whether these results hold up in a randomized, prospective study,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
Changing the continuous antibiotic prophylactic agent had no significant effect on the risk of a second infection in children with breakthrough urinary tract infections (UTIs), based on data from 62 children treated at a single center.
Continuous antibiotic prophylaxis (CAP) is often used for UTI prevention in children with febrile UTIs or anomalies that predispose them to UTIs, such as vesicoureteral reflux (VUR) or bladder and bowel dysfunction, said Lane M. Shish, MPH, of the University of Washington, Bothell, and colleagues in a poster (#1245) presented at the Pediatric Academic Societies annual meeting.
CAP, once initiated, is used until a planned endpoint or a breakthrough UTI, at which point alternative treatments usually include surgical intervention or a CAP agent change, the researchers said. However, changing the CAP agent is based on consensus without evidence of benefit, they noted.
To evaluate the potential effect of switching or maintaining CAP in cases of breakthrough UTIs, the researchers conducted a retrospective cohort study of all patients younger than 18 years on CAP for UTI prevention enrolled in a pediatric urology registry between January 2013 and August 2020.
All patients experienced a breakthrough UTI while on CAP; CAP was changed for 24 patients and left unchanged for 38 patients.
The primary outcome of second-breakthrough infections occurred in 12 of the changed CAP group and 22 of the unchanged group, with a relative risk of 0.86. The percentage of second breakthrough UTIs resistant to the current CAP was not significantly different between the changed and unchanged CAP groups (75% vs. 77%; P = 0.88).
The researchers also identified a rate ratio of 0.67 for a second breakthrough UTI in the changed CAP group, and found that approximately one-third of these patients (33.3%) developed antibiotic resistance to their initial antibiotic agent and the changed antibiotic agent.
The study findings were limited by several factors, including the retrospective design and small sample size, the researchers noted.
However, the results suggest that changing the CAP after an initial breakthrough UTI in children did not increase the risk of a second breakthrough UTI, and that CAP changing did introduce a risk of developing a second UTI with increased CAP resistance, the researchers noted. The results support leaving a child’s CAP unchanged after an initial breakthrough UTI, although additional research is needed to verify the findings, including studies involving a larger cohort with a multi-institutional prospective evaluation, they concluded.
Manage UTIs to reduce recurrence and resistance
“As we know, avoiding recurrent UTIs is important in preserving renal function in pediatric patients,” said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Avoiding recurrent UTIs is also important to avoid the development and spread of multidrug-resistant organisms,” he said.
Dr. Joos said he was surprised by some of the study findings. “I was surprised that, over the course of this 7-year retrospective review, overall only approximately 50% of patients with a first breakthrough UTI on CAP developed a second breakthrough UTI,” he noted. “Also, the relative risk of a second UTI was not significantly affected by whether the CAP antibiotic was changed after the first infection,” he said. “It would be interesting to see whether these results hold up in a randomized, prospective study,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
Changing the continuous antibiotic prophylactic agent had no significant effect on the risk of a second infection in children with breakthrough urinary tract infections (UTIs), based on data from 62 children treated at a single center.
Continuous antibiotic prophylaxis (CAP) is often used for UTI prevention in children with febrile UTIs or anomalies that predispose them to UTIs, such as vesicoureteral reflux (VUR) or bladder and bowel dysfunction, said Lane M. Shish, MPH, of the University of Washington, Bothell, and colleagues in a poster (#1245) presented at the Pediatric Academic Societies annual meeting.
CAP, once initiated, is used until a planned endpoint or a breakthrough UTI, at which point alternative treatments usually include surgical intervention or a CAP agent change, the researchers said. However, changing the CAP agent is based on consensus without evidence of benefit, they noted.
To evaluate the potential effect of switching or maintaining CAP in cases of breakthrough UTIs, the researchers conducted a retrospective cohort study of all patients younger than 18 years on CAP for UTI prevention enrolled in a pediatric urology registry between January 2013 and August 2020.
All patients experienced a breakthrough UTI while on CAP; CAP was changed for 24 patients and left unchanged for 38 patients.
The primary outcome of second-breakthrough infections occurred in 12 of the changed CAP group and 22 of the unchanged group, with a relative risk of 0.86. The percentage of second breakthrough UTIs resistant to the current CAP was not significantly different between the changed and unchanged CAP groups (75% vs. 77%; P = 0.88).
The researchers also identified a rate ratio of 0.67 for a second breakthrough UTI in the changed CAP group, and found that approximately one-third of these patients (33.3%) developed antibiotic resistance to their initial antibiotic agent and the changed antibiotic agent.
The study findings were limited by several factors, including the retrospective design and small sample size, the researchers noted.
However, the results suggest that changing the CAP after an initial breakthrough UTI in children did not increase the risk of a second breakthrough UTI, and that CAP changing did introduce a risk of developing a second UTI with increased CAP resistance, the researchers noted. The results support leaving a child’s CAP unchanged after an initial breakthrough UTI, although additional research is needed to verify the findings, including studies involving a larger cohort with a multi-institutional prospective evaluation, they concluded.
Manage UTIs to reduce recurrence and resistance
“As we know, avoiding recurrent UTIs is important in preserving renal function in pediatric patients,” said Tim Joos, MD, a Seattle-based clinician with a combination internal medicine/pediatrics practice, in an interview.
“Avoiding recurrent UTIs is also important to avoid the development and spread of multidrug-resistant organisms,” he said.
Dr. Joos said he was surprised by some of the study findings. “I was surprised that, over the course of this 7-year retrospective review, overall only approximately 50% of patients with a first breakthrough UTI on CAP developed a second breakthrough UTI,” he noted. “Also, the relative risk of a second UTI was not significantly affected by whether the CAP antibiotic was changed after the first infection,” he said. “It would be interesting to see whether these results hold up in a randomized, prospective study,” he added.
The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Joos had no financial conflicts to disclose, but serves as a member of the Pediatric News Editorial Advisory Board.
FROM PAS 2021