Antimicrobial-resistant infections

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

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

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

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

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

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

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.¹

Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.² A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.

PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV7^3,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.

Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B⁵ and we have been studying how 35B strains transitioned from commensal to otopathogen in children.⁶ Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.

The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.

Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Kaur R et al. Front Pediatr. 2021;9:722483.

2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44

3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.

4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..

5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.

6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.

Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.¹

Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.² A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.

PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV7^3,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.

Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B⁵ and we have been studying how 35B strains transitioned from commensal to otopathogen in children.⁶ Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.

The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.

Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Kaur R et al. Front Pediatr. 2021;9:722483.

2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44

3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.

4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..

5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.

6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.

Since the COVID-19 pandemic began, pediatricians have been seeing fewer cases of all respiratory illnesses, including acute otitis media (AOM). However, as I prepare this column, an uptick has commenced and likely will continue in an upward trajectory as we emerge from the pandemic into an endemic coronavirus era. Our group in Rochester, N.Y., has continued prospective studies of AOM throughout the pandemic. We found that nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus), Haemophilus influenzae, and Moraxella catarrhalis remained prevalent in our study cohort of children aged 6-36 months. However, with all the precautions of masking, social distancing, hand washing, and quick exclusion from day care when illness occurred, the frequency of detecting these common otopathogens decreased, as one might expect.¹

Leading up to the pandemic, we had an abundance of data to characterize AOM etiology and found that the cause of AOM continues to change following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13, Prevnar 13). Our most recent report on otopathogen distribution and antibiotic susceptibility covered the years 2015-2019.² A total of 589 children were enrolled prospectively and we collected 495 middle ear fluid samples (MEF) from 319 AOM cases using tympanocentesis. The frequency of isolates was H. influenzae (34%), pneumococcus (24%), and M. catarrhalis (15%). Beta-lactamase–positive H. influenzae strains were identified among 49% of the isolates, rendering them resistant to amoxicillin. PCV13 serotypes were infrequently isolated. However, we did isolate vaccine types (VTs) in some children from MEF, notably serotypes 19F, 19A, and 3. Non-PCV13 pneumococcus serotypes 35B, 23B, and 15B/C emerged as the most common serotypes. Amoxicillin resistance was identified among 25% of pneumococcal strains. Out of 16 antibiotics tested, 9 (56%) showed a significant increase in nonsusceptibility among pneumococcal isolates. 100% of M. catarrhalis isolates were beta-lactamase producers and therefore resistant to amoxicillin.

PCV13 has resulted in a decline in both invasive and noninvasive pneumococcal infections caused by strains expressing the 13 capsular serotypes included in the vaccine. However, the emergence of replacement serotypes occurred after introduction of PCV7^3,4 and continues to occur during the PCV13 era, as shown from the results presented here. Non-PCV13 serotypes accounted for more than 90% of MEF isolates during 2015-2019, with 35B, 21 and 23B being the most commonly isolated. Other emergent serotypes of potential importance were nonvaccine serotypes 15A, 15B, 15C, 23A and 11A. This is highly relevant because forthcoming higher-valency PCVs – PCV15 (manufactured by Merck) and PCV20 (manufactured by Pfizer) will not include many of the dominant capsular serotypes of pneumococcus strains causing AOM. Consequently, the impact of higher-valency PCVs on AOM will not be as great as was observed with the introduction of PCV7 or PCV13.

Of special interest, 22% of pneumococcus isolates from MEF were serotype 35B, making it the most prevalent. Recently we reported a significant rise in antibiotic nonsusceptibility in Spn isolates, contributed mainly by serotype 35B⁵ and we have been studying how 35B strains transitioned from commensal to otopathogen in children.⁶ Because serotype 35B strains are increasingly prevalent and often antibiotic resistant, absence of this serotype from PCV15 and PCV20 is cause for concern.

The frequency of isolation of H. influenzae and M. catarrhalis has remained stable across the PCV13 era as the No. 1 and No. 3 pathogens. Similarly, the production of beta-lactamase among strains causing AOM has remained stable at close to 50% and 100%, respectively. Use of amoxicillin, either high dose or standard dose, would not be expected to kill these bacteria.

Our study design has limitations. The population is derived from a predominantly middle-class, suburban population of children in upstate New York and may not be representative of other types of populations in the United States. The children are 6-36 months old, the age when most AOM occurs. MEF samples that were culture negative for bacteria were not further tested by polymerase chain reaction methods.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Kaur R et al. Front Pediatr. 2021;9:722483.

2. Kaur R et al. Euro J Clin Microbiol Infect Dis. 2021;41:37-44

3. Pelton SI et al. Pediatr Infect Disease J. 2004;23:1015-22.

4. Farrell DJ et al. Pediatr Infect Disease J. 2007;26:123-8..

5. Kaur R et al. Clin Infect Dis 2021;72(5):797-805.

6. Fuji N et al. Front Cell Infect Microbiol. 2021;11:744742.

Case

A 72-year-old woman with type 2 diabetes mellitus presents with acute dysuria, fever, and flank pain. She had a urinary tract infection (UTI) 3 months prior treated with nitrofurantoin. Temperature is 102° F, heart rate 112 beats per minute, and the remainder of vital signs are normal. She has left costovertebral angle tenderness. Urine microscopy shows 70 WBCs per high power field and bacteria. Is this urinary tract infection complicated?

Background

The urinary tract is divided into the upper tract, which includes the kidneys and ureters, and the lower urinary tract, which includes the bladder, urethra, and prostate. Infection of the lower urinary tract is referred to as cystitis while infection of the upper urinary tract is pyelonephritis. A UTI is the colonization of pathogen(s) within the urinary system that causes an inflammatory response resulting in symptoms and requiring treatment. UTIs occur when there is reduced urine flow, an increase in colonization risk, and when there are factors that facilitate ascent such as catheterization or incontinence.

There are an estimated 150 million cases of UTIs worldwide per year, accounting for $6 billion in health care expenditures.¹ In the inpatient setting, about 40% of nosocomial infections are associated with urinary catheters. This equates to about 1 million catheter-associated UTIs per year in the United States, and up to 40% of hospital gram-negative bacteremia per year are caused by UTIs.¹

UTIs are often classified as either uncomplicated or complicated infections, which can influence the depth of management. UTIs have a wide spectrum of symptoms and can manifest anywhere from mild dysuria treated successfully with outpatient antibiotics to florid sepsis. Uncomplicated simple cystitis is often treated as an outpatient with oral nitrofurantoin or trimethoprim-sulfamethoxazole.² Complicated UTIs are treated with broader antimicrobial coverage, and depending on severity, could require intravenous antibiotics. Many factors affect how a UTI manifests and determining whether an infection is “uncomplicated” or “complicated” is an important first step in guiding management. Unfortunately, there are differing classifications of “complicated” UTIs, making it a complicated issue itself. We outline two common approaches.
 

Anatomic approach

A commonly recognized definition is from the American Urological Association, which states that complicated UTIs are symptomatic cases associated with the presence of “underlying, predisposing conditions and not necessarily clinical severity, invasiveness, or complications.”³ These factors include structural or functional urinary tract abnormalities or urinary instrumentation (see Table 1). These predisposing conditions can increase microbial colonization and decrease therapy efficacy, thus increasing the frequency of infection and relapse.

This population of patients is at high risk of infections with more resistant bacteria such as extended-spectrum beta-lactamase (ESBL) producing Escherichia coli since they often lack the natural genitourinary barriers to infection. In addition, these patients more often undergo multiple antibiotic courses for their frequent infections, which also contributes to their risk of ESBL infections. Genitourinary abnormalities interfere with normal voiding, resulting in impaired flushing of bacteria. For instance, obstruction inhibits complete urinary drainage and increases the persistence of bacteria in biofilms, especially if there are stones or indwelling devices present. Biofilms usually contain a high concentration of organisms including Proteus mirabilis, Morgenella morganii, and Providencia spp.⁴ Keep in mind that, if there is an obstruction, the urinalysis might be without pyuria or bacteriuria.

Instrumentation increases infection risks through the direct introduction of bacteria into the genitourinary tract. Despite the efforts in maintaining sterility in urinary catheter placement, catheters provide a nidus for infection. Catheter-associated UTI (CAUTI) is defined by the Infectious Disease Society of America as UTIs that occur in patients with an indwelling catheter or who had a catheter removed for less than 48 hours who develop urinary symptoms and cultures positive for uropathogenic bacteria.⁴ Studies show that in general, patients with indwelling catheters will develop bacteriuria over time, with 10%-25% eventually developing symptoms.
 

Severity approach

There are other schools of thought that categorize uncomplicated versus complicated UTIs based on the severity of presentation (see Table 2). An uncomplicated UTI would be classified as symptoms and signs of simple cystitis limited to dysuria, frequency, urgency, and suprapubic pain. Using a symptom severity approach, systemic findings such as fever, chills, emesis, flank pain, costovertebral angle tenderness, or other findings of sepsis would be classified as a complicated UTI. These systemic findings would suggest an extension of infection beyond the bladder.

The argument for a symptomatic-based approach of classification is that the severity of symptoms should dictate the degree of management. Not all UTIs in the anatomic approach are severe. In fact, populations that are considered at risk for complicated UTIs by the AUA guidelines in Table 1 often have mild symptomatic cystitis or asymptomatic bacteriuria. Asymptomatic bacteriuria is the colonization of organisms in the urinary tract without active infection. For instance, bacteriuria is present in almost 100% of people with chronic indwelling catheters, 30%-40% of neurogenic bladder requiring intermittent catheterization, and 50% of elderly nursing home residents.⁴ Not all bacteriuria triggers enough of an inflammatory response to cause symptoms that require treatment.
 

Ultimate clinical judgment

Although there are multiple different society recommendations in distinguishing uncomplicated versus complicated UTIs, considering both anatomical and severity risk factors can better aid in clinical decision-making rather than abiding by one classification method alone.

Uncomplicated UTIs from the AUA guidelines can cause severe infections that might require longer courses of broad-spectrum antibiotics. On the other hand, people with anatomic abnormalities can present with mild symptoms that can be treated with a narrow-spectrum antibiotic for a standard time course. Recognizing the severity of the infection and using clinical judgment aids in antibiotic stewardship.

Although the existence of algorithmic approaches can help guide clinical judgment, accounting for the spectrum of host and bacterial factors should ultimately determine the complexity of the disease and management.³ Using clinical suspicion to determine when a UTI should be treated as a complicated infection can ensure effective treatment and decrease the likelihood of sepsis, renal scarring, or end-stage disease.⁵

Back to the case

The case presents an elderly woman with diabetes presenting with sepsis from a UTI. Because of a normal urinary tract and no prior instrumentation, by the AUA definition, she would be classified as an uncomplicated UTI; however, we would classify her as a complicated UTI based on the severity of her presentation. She has a fever, tachycardia, flank pain, and costovertebral angle tenderness that are evidence of infection extending beyond the bladder. She has sepsis warranting inpatient management. Prior urine culture results could aid in determining empiric treatment while waiting for new cultures. In her case, an intravenous antibiotic with broad gram-negative coverage such as ceftriaxone would be appropriate.

Bottom line

There are multiple interpretations of complicated UTIs including both an anatomical and severity approach. Clinical judgment regarding infection severity should determine the depth of management.

Dr. Vu is a hospitalist at the University of Kentucky, Lexington. Dr. Gray is a hospitalist at the University of Kentucky and the Lexington Veterans Affairs Medical Center.

References

1. Folk CS. AUA Core Curriculum: Urinary Tract Infection (Adult). 2021 Mar 1. https://university.auanet.org/core_topic.cfm?coreid=92.

2. Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.

3. Johnson JR. Definition of Complicated Urinary Tract Infection. Clin Infect Dis. 2017 February 15;64(4):529. doi: 10.1093/cid/ciw751.

4. Nicolle LE, AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005;16(6):349-60. doi: 10.1155/2005/385768.

5. Melekos MD and Naber KG. Complicated urinary tract infections. Int J Antimicrob Agents. 2000;15(4):247-56. doi: 10.1016/s0924-8579(00)00168-0.
 

Key points

• The anatomical approach to defining complicated UTIs considers the presence of underlying, predisposing conditions such as structurally or functionally abnormal genitourinary tract or urinary instrumentation or foreign bodies.
• The severity approach to defining complicated UTIs considers the severity of presentation including the presence of systemic manifestations.
• Both approaches should consider populations that are at risk for recurrent or multidrug-resistant infections and infections that can lead to high morbidity.
• Either approach can be used as a guide, but neither should replace clinical suspicion and judgment in determining the depth of treatment.

Additional reading

Choe HS et al. Summary of the UAA‐AAUS guidelines for urinary tract infections. Int J Urol. 2018 Mar;25(3):175-85. doi:10.1111/iju.13493.

Nicolle LE et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005 Mar;40(5):643-54. doi: 10.1086/427507.

Wagenlehner FME et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020 Oct;17:586-600. doi:10.1038/s41585-020-0362-4.

Wallace DW et al. Urinalysis: A simple test with complicated interpretation. J Urgent Care Med. 2020 July-Aug;14(10):11-4.

Quiz

A 68-year-old woman with type 2 diabetes mellitus presents to the emergency department with acute fever, chills, dysuria, frequency, and suprapubic pain. She has associated nausea, malaise, and fatigue. She takes metformin and denies recent antibiotic use. Her temperature is 102.8° F, heart rate 118 beats per minute, blood pressure 118/71 mm Hg, and her respiratory rate is 24 breaths per minute. She is ill-appearing and has mild suprapubic tenderness. White blood cell count is 18 k/mcL. Urinalysis is positive for leukocyte esterase, nitrites, and bacteria. Urine microscopy has 120 white blood cells per high power field. What is the most appropriate treatment?

A. Azithromycin

B. Ceftriaxone

C. Cefepime and vancomycin

D. Nitrofurantoin

The answer is B. The patient presents with sepsis secondary to a urinary tract infection. Using the anatomic approach this would be classified as uncomplicated. Using the severity approach, this would be classified as a complicated urinary tract infection. With fever, chills, and signs of sepsis, it’s likely her infection extends beyond the bladder. Given the severity of her presentation, we’d favor treating her as a complicated urinary tract infection with intravenous ceftriaxone. There is no suggestion of resistance or additional MRSA risk factors requiring intravenous vancomycin or cefepime. Nitrofurantoin, although a first-line treatment for uncomplicated cystitis, would not be appropriate if there is suspicion infection extends beyond the bladder. Azithromycin is a first-line option for chlamydia trachomatis, but not a urinary tract infection.




 

Case

A 72-year-old woman with type 2 diabetes mellitus presents with acute dysuria, fever, and flank pain. She had a urinary tract infection (UTI) 3 months prior treated with nitrofurantoin. Temperature is 102° F, heart rate 112 beats per minute, and the remainder of vital signs are normal. She has left costovertebral angle tenderness. Urine microscopy shows 70 WBCs per high power field and bacteria. Is this urinary tract infection complicated?

Background

The urinary tract is divided into the upper tract, which includes the kidneys and ureters, and the lower urinary tract, which includes the bladder, urethra, and prostate. Infection of the lower urinary tract is referred to as cystitis while infection of the upper urinary tract is pyelonephritis. A UTI is the colonization of pathogen(s) within the urinary system that causes an inflammatory response resulting in symptoms and requiring treatment. UTIs occur when there is reduced urine flow, an increase in colonization risk, and when there are factors that facilitate ascent such as catheterization or incontinence.

There are an estimated 150 million cases of UTIs worldwide per year, accounting for $6 billion in health care expenditures.¹ In the inpatient setting, about 40% of nosocomial infections are associated with urinary catheters. This equates to about 1 million catheter-associated UTIs per year in the United States, and up to 40% of hospital gram-negative bacteremia per year are caused by UTIs.¹

UTIs are often classified as either uncomplicated or complicated infections, which can influence the depth of management. UTIs have a wide spectrum of symptoms and can manifest anywhere from mild dysuria treated successfully with outpatient antibiotics to florid sepsis. Uncomplicated simple cystitis is often treated as an outpatient with oral nitrofurantoin or trimethoprim-sulfamethoxazole.² Complicated UTIs are treated with broader antimicrobial coverage, and depending on severity, could require intravenous antibiotics. Many factors affect how a UTI manifests and determining whether an infection is “uncomplicated” or “complicated” is an important first step in guiding management. Unfortunately, there are differing classifications of “complicated” UTIs, making it a complicated issue itself. We outline two common approaches.
 

Anatomic approach

A commonly recognized definition is from the American Urological Association, which states that complicated UTIs are symptomatic cases associated with the presence of “underlying, predisposing conditions and not necessarily clinical severity, invasiveness, or complications.”³ These factors include structural or functional urinary tract abnormalities or urinary instrumentation (see Table 1). These predisposing conditions can increase microbial colonization and decrease therapy efficacy, thus increasing the frequency of infection and relapse.

This population of patients is at high risk of infections with more resistant bacteria such as extended-spectrum beta-lactamase (ESBL) producing Escherichia coli since they often lack the natural genitourinary barriers to infection. In addition, these patients more often undergo multiple antibiotic courses for their frequent infections, which also contributes to their risk of ESBL infections. Genitourinary abnormalities interfere with normal voiding, resulting in impaired flushing of bacteria. For instance, obstruction inhibits complete urinary drainage and increases the persistence of bacteria in biofilms, especially if there are stones or indwelling devices present. Biofilms usually contain a high concentration of organisms including Proteus mirabilis, Morgenella morganii, and Providencia spp.⁴ Keep in mind that, if there is an obstruction, the urinalysis might be without pyuria or bacteriuria.

Instrumentation increases infection risks through the direct introduction of bacteria into the genitourinary tract. Despite the efforts in maintaining sterility in urinary catheter placement, catheters provide a nidus for infection. Catheter-associated UTI (CAUTI) is defined by the Infectious Disease Society of America as UTIs that occur in patients with an indwelling catheter or who had a catheter removed for less than 48 hours who develop urinary symptoms and cultures positive for uropathogenic bacteria.⁴ Studies show that in general, patients with indwelling catheters will develop bacteriuria over time, with 10%-25% eventually developing symptoms.
 

Severity approach

There are other schools of thought that categorize uncomplicated versus complicated UTIs based on the severity of presentation (see Table 2). An uncomplicated UTI would be classified as symptoms and signs of simple cystitis limited to dysuria, frequency, urgency, and suprapubic pain. Using a symptom severity approach, systemic findings such as fever, chills, emesis, flank pain, costovertebral angle tenderness, or other findings of sepsis would be classified as a complicated UTI. These systemic findings would suggest an extension of infection beyond the bladder.

The argument for a symptomatic-based approach of classification is that the severity of symptoms should dictate the degree of management. Not all UTIs in the anatomic approach are severe. In fact, populations that are considered at risk for complicated UTIs by the AUA guidelines in Table 1 often have mild symptomatic cystitis or asymptomatic bacteriuria. Asymptomatic bacteriuria is the colonization of organisms in the urinary tract without active infection. For instance, bacteriuria is present in almost 100% of people with chronic indwelling catheters, 30%-40% of neurogenic bladder requiring intermittent catheterization, and 50% of elderly nursing home residents.⁴ Not all bacteriuria triggers enough of an inflammatory response to cause symptoms that require treatment.
 

Ultimate clinical judgment

Although there are multiple different society recommendations in distinguishing uncomplicated versus complicated UTIs, considering both anatomical and severity risk factors can better aid in clinical decision-making rather than abiding by one classification method alone.

Uncomplicated UTIs from the AUA guidelines can cause severe infections that might require longer courses of broad-spectrum antibiotics. On the other hand, people with anatomic abnormalities can present with mild symptoms that can be treated with a narrow-spectrum antibiotic for a standard time course. Recognizing the severity of the infection and using clinical judgment aids in antibiotic stewardship.

Although the existence of algorithmic approaches can help guide clinical judgment, accounting for the spectrum of host and bacterial factors should ultimately determine the complexity of the disease and management.³ Using clinical suspicion to determine when a UTI should be treated as a complicated infection can ensure effective treatment and decrease the likelihood of sepsis, renal scarring, or end-stage disease.⁵

Back to the case

The case presents an elderly woman with diabetes presenting with sepsis from a UTI. Because of a normal urinary tract and no prior instrumentation, by the AUA definition, she would be classified as an uncomplicated UTI; however, we would classify her as a complicated UTI based on the severity of her presentation. She has a fever, tachycardia, flank pain, and costovertebral angle tenderness that are evidence of infection extending beyond the bladder. She has sepsis warranting inpatient management. Prior urine culture results could aid in determining empiric treatment while waiting for new cultures. In her case, an intravenous antibiotic with broad gram-negative coverage such as ceftriaxone would be appropriate.

Bottom line

There are multiple interpretations of complicated UTIs including both an anatomical and severity approach. Clinical judgment regarding infection severity should determine the depth of management.

Dr. Vu is a hospitalist at the University of Kentucky, Lexington. Dr. Gray is a hospitalist at the University of Kentucky and the Lexington Veterans Affairs Medical Center.

References

1. Folk CS. AUA Core Curriculum: Urinary Tract Infection (Adult). 2021 Mar 1. https://university.auanet.org/core_topic.cfm?coreid=92.

2. Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.

3. Johnson JR. Definition of Complicated Urinary Tract Infection. Clin Infect Dis. 2017 February 15;64(4):529. doi: 10.1093/cid/ciw751.

4. Nicolle LE, AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005;16(6):349-60. doi: 10.1155/2005/385768.

5. Melekos MD and Naber KG. Complicated urinary tract infections. Int J Antimicrob Agents. 2000;15(4):247-56. doi: 10.1016/s0924-8579(00)00168-0.
 

Key points

• The anatomical approach to defining complicated UTIs considers the presence of underlying, predisposing conditions such as structurally or functionally abnormal genitourinary tract or urinary instrumentation or foreign bodies.
• The severity approach to defining complicated UTIs considers the severity of presentation including the presence of systemic manifestations.
• Both approaches should consider populations that are at risk for recurrent or multidrug-resistant infections and infections that can lead to high morbidity.
• Either approach can be used as a guide, but neither should replace clinical suspicion and judgment in determining the depth of treatment.

Additional reading

Choe HS et al. Summary of the UAA‐AAUS guidelines for urinary tract infections. Int J Urol. 2018 Mar;25(3):175-85. doi:10.1111/iju.13493.

Nicolle LE et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005 Mar;40(5):643-54. doi: 10.1086/427507.

Wagenlehner FME et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020 Oct;17:586-600. doi:10.1038/s41585-020-0362-4.

Wallace DW et al. Urinalysis: A simple test with complicated interpretation. J Urgent Care Med. 2020 July-Aug;14(10):11-4.

Quiz

A 68-year-old woman with type 2 diabetes mellitus presents to the emergency department with acute fever, chills, dysuria, frequency, and suprapubic pain. She has associated nausea, malaise, and fatigue. She takes metformin and denies recent antibiotic use. Her temperature is 102.8° F, heart rate 118 beats per minute, blood pressure 118/71 mm Hg, and her respiratory rate is 24 breaths per minute. She is ill-appearing and has mild suprapubic tenderness. White blood cell count is 18 k/mcL. Urinalysis is positive for leukocyte esterase, nitrites, and bacteria. Urine microscopy has 120 white blood cells per high power field. What is the most appropriate treatment?

A. Azithromycin

B. Ceftriaxone

C. Cefepime and vancomycin

D. Nitrofurantoin

The answer is B. The patient presents with sepsis secondary to a urinary tract infection. Using the anatomic approach this would be classified as uncomplicated. Using the severity approach, this would be classified as a complicated urinary tract infection. With fever, chills, and signs of sepsis, it’s likely her infection extends beyond the bladder. Given the severity of her presentation, we’d favor treating her as a complicated urinary tract infection with intravenous ceftriaxone. There is no suggestion of resistance or additional MRSA risk factors requiring intravenous vancomycin or cefepime. Nitrofurantoin, although a first-line treatment for uncomplicated cystitis, would not be appropriate if there is suspicion infection extends beyond the bladder. Azithromycin is a first-line option for chlamydia trachomatis, but not a urinary tract infection.




 

Case

A 72-year-old woman with type 2 diabetes mellitus presents with acute dysuria, fever, and flank pain. She had a urinary tract infection (UTI) 3 months prior treated with nitrofurantoin. Temperature is 102° F, heart rate 112 beats per minute, and the remainder of vital signs are normal. She has left costovertebral angle tenderness. Urine microscopy shows 70 WBCs per high power field and bacteria. Is this urinary tract infection complicated?

Background

The urinary tract is divided into the upper tract, which includes the kidneys and ureters, and the lower urinary tract, which includes the bladder, urethra, and prostate. Infection of the lower urinary tract is referred to as cystitis while infection of the upper urinary tract is pyelonephritis. A UTI is the colonization of pathogen(s) within the urinary system that causes an inflammatory response resulting in symptoms and requiring treatment. UTIs occur when there is reduced urine flow, an increase in colonization risk, and when there are factors that facilitate ascent such as catheterization or incontinence.

There are an estimated 150 million cases of UTIs worldwide per year, accounting for $6 billion in health care expenditures.¹ In the inpatient setting, about 40% of nosocomial infections are associated with urinary catheters. This equates to about 1 million catheter-associated UTIs per year in the United States, and up to 40% of hospital gram-negative bacteremia per year are caused by UTIs.¹

UTIs are often classified as either uncomplicated or complicated infections, which can influence the depth of management. UTIs have a wide spectrum of symptoms and can manifest anywhere from mild dysuria treated successfully with outpatient antibiotics to florid sepsis. Uncomplicated simple cystitis is often treated as an outpatient with oral nitrofurantoin or trimethoprim-sulfamethoxazole.² Complicated UTIs are treated with broader antimicrobial coverage, and depending on severity, could require intravenous antibiotics. Many factors affect how a UTI manifests and determining whether an infection is “uncomplicated” or “complicated” is an important first step in guiding management. Unfortunately, there are differing classifications of “complicated” UTIs, making it a complicated issue itself. We outline two common approaches.
 

Anatomic approach

A commonly recognized definition is from the American Urological Association, which states that complicated UTIs are symptomatic cases associated with the presence of “underlying, predisposing conditions and not necessarily clinical severity, invasiveness, or complications.”³ These factors include structural or functional urinary tract abnormalities or urinary instrumentation (see Table 1). These predisposing conditions can increase microbial colonization and decrease therapy efficacy, thus increasing the frequency of infection and relapse.

This population of patients is at high risk of infections with more resistant bacteria such as extended-spectrum beta-lactamase (ESBL) producing Escherichia coli since they often lack the natural genitourinary barriers to infection. In addition, these patients more often undergo multiple antibiotic courses for their frequent infections, which also contributes to their risk of ESBL infections. Genitourinary abnormalities interfere with normal voiding, resulting in impaired flushing of bacteria. For instance, obstruction inhibits complete urinary drainage and increases the persistence of bacteria in biofilms, especially if there are stones or indwelling devices present. Biofilms usually contain a high concentration of organisms including Proteus mirabilis, Morgenella morganii, and Providencia spp.⁴ Keep in mind that, if there is an obstruction, the urinalysis might be without pyuria or bacteriuria.

Instrumentation increases infection risks through the direct introduction of bacteria into the genitourinary tract. Despite the efforts in maintaining sterility in urinary catheter placement, catheters provide a nidus for infection. Catheter-associated UTI (CAUTI) is defined by the Infectious Disease Society of America as UTIs that occur in patients with an indwelling catheter or who had a catheter removed for less than 48 hours who develop urinary symptoms and cultures positive for uropathogenic bacteria.⁴ Studies show that in general, patients with indwelling catheters will develop bacteriuria over time, with 10%-25% eventually developing symptoms.
 

Severity approach

There are other schools of thought that categorize uncomplicated versus complicated UTIs based on the severity of presentation (see Table 2). An uncomplicated UTI would be classified as symptoms and signs of simple cystitis limited to dysuria, frequency, urgency, and suprapubic pain. Using a symptom severity approach, systemic findings such as fever, chills, emesis, flank pain, costovertebral angle tenderness, or other findings of sepsis would be classified as a complicated UTI. These systemic findings would suggest an extension of infection beyond the bladder.

The argument for a symptomatic-based approach of classification is that the severity of symptoms should dictate the degree of management. Not all UTIs in the anatomic approach are severe. In fact, populations that are considered at risk for complicated UTIs by the AUA guidelines in Table 1 often have mild symptomatic cystitis or asymptomatic bacteriuria. Asymptomatic bacteriuria is the colonization of organisms in the urinary tract without active infection. For instance, bacteriuria is present in almost 100% of people with chronic indwelling catheters, 30%-40% of neurogenic bladder requiring intermittent catheterization, and 50% of elderly nursing home residents.⁴ Not all bacteriuria triggers enough of an inflammatory response to cause symptoms that require treatment.
 

Ultimate clinical judgment

Although there are multiple different society recommendations in distinguishing uncomplicated versus complicated UTIs, considering both anatomical and severity risk factors can better aid in clinical decision-making rather than abiding by one classification method alone.

Uncomplicated UTIs from the AUA guidelines can cause severe infections that might require longer courses of broad-spectrum antibiotics. On the other hand, people with anatomic abnormalities can present with mild symptoms that can be treated with a narrow-spectrum antibiotic for a standard time course. Recognizing the severity of the infection and using clinical judgment aids in antibiotic stewardship.

Although the existence of algorithmic approaches can help guide clinical judgment, accounting for the spectrum of host and bacterial factors should ultimately determine the complexity of the disease and management.³ Using clinical suspicion to determine when a UTI should be treated as a complicated infection can ensure effective treatment and decrease the likelihood of sepsis, renal scarring, or end-stage disease.⁵

Back to the case

The case presents an elderly woman with diabetes presenting with sepsis from a UTI. Because of a normal urinary tract and no prior instrumentation, by the AUA definition, she would be classified as an uncomplicated UTI; however, we would classify her as a complicated UTI based on the severity of her presentation. She has a fever, tachycardia, flank pain, and costovertebral angle tenderness that are evidence of infection extending beyond the bladder. She has sepsis warranting inpatient management. Prior urine culture results could aid in determining empiric treatment while waiting for new cultures. In her case, an intravenous antibiotic with broad gram-negative coverage such as ceftriaxone would be appropriate.

Bottom line

There are multiple interpretations of complicated UTIs including both an anatomical and severity approach. Clinical judgment regarding infection severity should determine the depth of management.

Dr. Vu is a hospitalist at the University of Kentucky, Lexington. Dr. Gray is a hospitalist at the University of Kentucky and the Lexington Veterans Affairs Medical Center.

References

1. Folk CS. AUA Core Curriculum: Urinary Tract Infection (Adult). 2021 Mar 1. https://university.auanet.org/core_topic.cfm?coreid=92.

2. Gupta K et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20. doi: 10.1093/cid/ciq257.

3. Johnson JR. Definition of Complicated Urinary Tract Infection. Clin Infect Dis. 2017 February 15;64(4):529. doi: 10.1093/cid/ciw751.

4. Nicolle LE, AMMI Canada Guidelines Committee. Complicated urinary tract infection in adults. Can J Infect Dis Med Microbiol. 2005;16(6):349-60. doi: 10.1155/2005/385768.

5. Melekos MD and Naber KG. Complicated urinary tract infections. Int J Antimicrob Agents. 2000;15(4):247-56. doi: 10.1016/s0924-8579(00)00168-0.
 

Key points

• The anatomical approach to defining complicated UTIs considers the presence of underlying, predisposing conditions such as structurally or functionally abnormal genitourinary tract or urinary instrumentation or foreign bodies.
• The severity approach to defining complicated UTIs considers the severity of presentation including the presence of systemic manifestations.
• Both approaches should consider populations that are at risk for recurrent or multidrug-resistant infections and infections that can lead to high morbidity.
• Either approach can be used as a guide, but neither should replace clinical suspicion and judgment in determining the depth of treatment.

Additional reading

Choe HS et al. Summary of the UAA‐AAUS guidelines for urinary tract infections. Int J Urol. 2018 Mar;25(3):175-85. doi:10.1111/iju.13493.

Nicolle LE et al. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005 Mar;40(5):643-54. doi: 10.1086/427507.

Wagenlehner FME et al. Epidemiology, definition and treatment of complicated urinary tract infections. Nat Rev Urol. 2020 Oct;17:586-600. doi:10.1038/s41585-020-0362-4.

Wallace DW et al. Urinalysis: A simple test with complicated interpretation. J Urgent Care Med. 2020 July-Aug;14(10):11-4.

Quiz

A 68-year-old woman with type 2 diabetes mellitus presents to the emergency department with acute fever, chills, dysuria, frequency, and suprapubic pain. She has associated nausea, malaise, and fatigue. She takes metformin and denies recent antibiotic use. Her temperature is 102.8° F, heart rate 118 beats per minute, blood pressure 118/71 mm Hg, and her respiratory rate is 24 breaths per minute. She is ill-appearing and has mild suprapubic tenderness. White blood cell count is 18 k/mcL. Urinalysis is positive for leukocyte esterase, nitrites, and bacteria. Urine microscopy has 120 white blood cells per high power field. What is the most appropriate treatment?

A. Azithromycin

B. Ceftriaxone

C. Cefepime and vancomycin

D. Nitrofurantoin

The answer is B. The patient presents with sepsis secondary to a urinary tract infection. Using the anatomic approach this would be classified as uncomplicated. Using the severity approach, this would be classified as a complicated urinary tract infection. With fever, chills, and signs of sepsis, it’s likely her infection extends beyond the bladder. Given the severity of her presentation, we’d favor treating her as a complicated urinary tract infection with intravenous ceftriaxone. There is no suggestion of resistance or additional MRSA risk factors requiring intravenous vancomycin or cefepime. Nitrofurantoin, although a first-line treatment for uncomplicated cystitis, would not be appropriate if there is suspicion infection extends beyond the bladder. Azithromycin is a first-line option for chlamydia trachomatis, but not a urinary tract infection.




 

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

Clinicians are prescribing clarithromycin at high rates for Helicobacter pylori infections, despite increasing resistance to this antibiotic, researchers say.

In an analysis of 1 million U.S. prescriptions for H. pylori infections, 80% contained clarithromycin, said Carol Rockett, PharmD, associate vice president of RedHill Biopharma in Raleigh, N.C.

Dr. Rockett presented the findings at the annual meeting of the American College of Gastroenterology.

“Multiple talks [at the meeting] have suggested that the use of clarithromycin in H. pylori is obsolete,” she told this news organization. “Clarithromycin is particularly ineffective in people with a genetic variant that causes rapid metabolism.”

According to the 2017 ACG clinical guideline for treating H. pylori, patients diagnosed with this infection should be asked about their previous antibiotic exposure prior to treatment.

Additionally, clinicians should prescribe clarithromycin triple therapy with a proton pump inhibitor (PPI) and amoxicillin or metronidazole as a first-line treatment only in “regions where H. pylori clarithromycin resistance is known to be less than 15%” and in patients with no previous history of macrolide exposure.

The guideline puts bismuth quadruple therapy, consisting of a PPI, bismuth, tetracycline, and a nitroimidazole, at the top of its list of six alternative first-line therapies. However, three of the six alternatives include clarithromycin.
 

ERADICATE Hp and ERADICATE Hp2

To understand how U.S. physicians are treating patients with H. pylori, Dr. Rockett’s colleagues analyzed data from two phase 3 clinical trials of RedHill’s RHB-105 (Talicia): ERADICATE Hp and ERADICATE Hp2.

RHB-105 is an all-in‐one combination of omeprazole (40 mg), amoxicillin (1,000 mg), and rifabutin (50 mg) that the Food and Drug Administration approved for treatment of H pylori in 2019.

The researchers followed 38 subjects from ERADICATE Hp who remained positive for H. pylori after the study’s completion. A total of 33 had received a placebo in that trial, while the other 5 had received RHB-105.

The researchers obtained data on 31 of these patients. The overall cure rate was 61.3%. Of the 31 patients, 27 received a regimen including clarithromycin. Their cure rate was 59.3%.

Turning to ERADICATE Hp2, the researchers obtained data on 94 patients whose H. pylori infections persisted after the trial. Of those, 67 had received an active comparator (amoxicillin 250 mg and omeprazole 10 mg) and 27 had received RHB-105.

The overall cure rate was 56.2%. For the 48 subjects who received therapies including clarithromycin, the cure rate was 60.4%. For the 22 subjects who received a bismuth-based quadruple regimen, the cure rate was 45.4%.

In another analysis, the researchers crunched 12 months of numbers from IQVIA PharMetrics Plus medical and prescription claim database of over 1 million prescriptions for H. pylori. They found that 80% of the prescriptions made by gastroenterologists were for regimens containing clarithromycin. That proportion increased to 84% for physician assistants and internists, 85% for nurse practitioners, 86% for family practitioners, and 89% for general practitioners.

Finally, the researchers also analyzed patients for CYP2C19 gene status. They tested 65 subjects who received RHB-105 in ERADICATE Hp and all 445 subjects in ERADICATE Hp2. They found that 58.5% in ERADICATE Hp and 48.6% in ERADICATE Hp2 were normal metabolizers.

In 20 normal metabolizers who received clarithromycin, the drug eradicated the infection in 16 (80%). Out of 11 rapid metabolizers, clarithromycin eradicated the bacterium in 2 (18.2%). The difference was statistically significant (P = .0017).

“With clarithromycin, you can see that the efficacy is reduced in those patients who are rapid metabolizers,” Dr. Rockett said. “We didn’t see that with rifabutin [one of the drugs in RHB-105].”

Jared Magee, DO, MPH, a gastroenterology fellow at the Walter Reed National Military Medical Center in Bethesda, Md., said in treating H. pylori infections, he checks the patients’ medical records to see what antibiotics they have received in the past and generally begins treatment with the bismuth quadruple therapy.

“There is education needed to get the data out there that clarithromycin-based therapies may not be the right choice for patients,” he said. “There is a subset who will do well with it, but I think where we’re at now, with the frequency of macrolide prescriptions for other conditions, that clarithromycin is going to be a difficult therapy for a lot of people.”

Clinicians who are not gastroenterologists may not be aware of the guideline promulgated by the ACG, he pointed out.

Dr. Rockett is an employee of RedHill Biopharma. Dr. Magee has disclosed no relevant financial relationships. The study was funded by RedHill Biopharma.

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

Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

Most children with simple febrile seizures (SFSs) can be safely managed without lumbar puncture or other diagnostic tests without risking delayed diagnosis of bacterial meningitis, new data gathered from a 15-year span suggest.

Vidya R. Raghavan, MD, with the division of emergency medicine at Boston Children’s Hospital and Harvard Medical School, also in Boston, published their findings in Pediatrics.

In 2011, researchers published the American Academy of Pediatrics simple febrile seizure guideline, which recommends limiting lumbar puncture to non–low-risk patients. The guidelines also specified that neuroimaging and hematologic testing are not routinely recommended.

Dr. Raghavan and coauthors studied evaluation and management trends of the patients before and after the guidelines. They identified 142,121 children diagnosed with SFS who presented to 1 of 49 pediatric tertiary EDs and met other study criteria. Changes in management of SFS had started years before the guideline and positive effects continued after the guideline publication.

Researchers found a significant 95% decline in rates of lumbar puncture between 2005 and 2019 from 11.6% (95% confidence interval, 10.8%-12.4%) of children in 2005 to 0.6% (95% CI, 0.5%-0.8%; P < .001) in 2019. The most significant declines were among infants 6 months to 1 year.

“We found similar declines in rates of diagnostic laboratory and radiologic testing, intravenous antibiotic administration, hospitalization, and costs,” the authors wrote.

“Importantly,” they wrote, “the decrease in testing was not associated with a concurrent increase in delayed diagnoses of bacterial meningitis.”

The number of hospital admissions and total costs also dropped significantly over the 15-year span of the study. After adjusting for inflation, the authors wrote, costs dropped from an average $1,523 in 2005 to $605 (P < .001) in 2019.

Among first-time presentations for SFSs, 19.2% (95% CI, 18.3%-20.2%) resulted in admission in 2005. That rate dropped to 5.2% (95% CI, 4.8%-5.6%) in 2019 (P < .001), although the authors noted that trend largely plateaued after the guideline was published.

“Our findings are consistent with smaller studies published before 2011 in which researchers found declining rates of LP [lumbar puncture] in children presenting to the ED with their first SFS,” the authors wrote.

Mercedes Blackstone, MD, an emergency physician at the Children’s Hospital of Philadelphia, said in an interview that the paper offers reassurance for changed practice over the last decade.

She said there was substantial relief in pediatrics when the 2011 guidelines recognized formally that protocols were outdated, especially as bacterial meningitis had become increasingly rare with widespread use of pneumococcal and Haemophilus influenzae vaccines. Practitioners had already started to limit the spinal taps on their own.

“We were not really complying with the prior recommendation to do a spinal tap in all those children because it often felt like doing a pretty invasive procedure with a very low yield in what was often a very well child in front of you,” she said.

In 2007, the authors noted, a few years before the guidelines, rates of bacterial meningitis had decreased to 7 per 100,000 in children aged between 2 and 23 months and 0.56 per 100,000 in children aged between 2 and 10 years.

However, Dr. Blackstone said, there was still a worry among some practitioners that there could be missed cases of bacterial meningitis.

“It’s very helpful to see that in all those years, the guidelines have been very validated and there were really no missed cases,” said Dr. Blackstone, author of CHOP’s febrile seizures clinical pathway.

It was good to see the number of CT scans drop as well, she said. Dr. Raghavan’s team found they decreased from 10.6% to 1.6%; P < .001, over the study period.

“Earlier work had shown that there was still a fair amount of head CTs happening and that’s radiation to the young brain,” Dr. Blackstone noted. “This is great news.”

Dr. Blackstone said it was great to see so many children from so many children’s hospitals included in the study.

The paper confirmed that “we’ve reduced a lot of unnecessary testing, saved a lot of cost, and had no increased risk to the patients,” she said.

Dr. Blackstone pointed out that the authors include a limitation that many children are seen in nonpediatric centers in community adult ED and she said those settings tend to have more testing.

“Hopefully, these guidelines have penetrated into the whole community,” she said. “With this paper they should feel reassured that they can spare children some of these tests and procedures.”

Dr. Raghavan and Dr. Blackstone declared no relevant financial relationships.

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

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.

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

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.

LAS VEGAS – An oral treatment with freeze-dried human stool can successfully treat Clostridioides difficile infections by increasing the diversity of microorganisms in the colon, researchers say.

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.

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.

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.

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.