Clostridium difficile: Not just for adults

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].

The true prevalence and meaning of Clostridium difficile detection in children remains an issue despite a known high prevalence of asymptomatic colonization in children during the first 3 years of life. Distinguishing C. difficile disease from colonization is difficult. Endoscopy can identify some severe C. difficile disease, but what about mild to moderate C. difficile infection?

A passive Centers for Disease Control and Prevention surveillance study (Pediatrics 2014;133:651-8) helps in understanding C. difficile prevalence by documenting the relatively high prevalence of community-acquired C. difficile often associated with use of common oral antibiotics and possibly because of the emergence of the NAP1 strain, which is also emerging in adults. But distinguishing infection from colonization remains an issue. The data have implications for everyday pediatric care.

Methods

Children aged 1-17 years from 10 U.S. states were studied during 2011-2012. C. difficile "cases" were defined via a positive toxin or a molecular test ordered as part of standard care. Standard of care testing for other selected gastrointestinal pathogens and data from medical records were collected. Within 3-6 months of the C. difficile–positive test, a convenience sample of families (about 9%) underwent a telephone interview.

Factors in C. difficile detection

C. difficile was detected in 944 stools from 885 children with no gender difference. The highest rates per 100,000 by race were in whites (23.9) vs. nonwhites (17.4), and in 12- to 23-month-olds (66.3). Overall, 71% of detections were categorized from charted data as community acquired. Only 17% were associated with outpatient health care and 12% with inpatient care.

Antibiotic use in the 14 days before a C. difficile–positive stool was 33% among all cases with no age group differences. Cephalosporins (41%) and amoxicillin/clavulanate (28%) were most common. Among 84 cases also later interviewed by phone, antibiotic use was more frequent (73%); penicillins (39%) and cephalosporins (44%) were the antibiotics most commonly used in this subset of patients. Indications were most often otitis, sinusitis, or upper respiratory infection. In the phone interviews, outpatient office visits were a more frequent (97%) health care exposure than in the overall case population.

Signs and symptoms were mild and similar in all age groups. Diarrhea was not present in 28%. Coinfection with another enteric pathogen was identified in 3% of 535 tested samples: bacterial (n = 12), protozoal (n = 4), and viral (n = 1) – and more common in 2- to 9-year-olds (P = .03). Peripheral WBC counts were abnormal (greater than 15, 000/mm³) in only 7%. There was radiographic evidence of ileus in three and pseudomembranous colitis developed in five cases. Cases were defined as severe in 8% with no age preponderance. There were no deaths.

Infection vs. colonization?

The authors reason that similar clinical presentations and symptom severity at all ages means that detection of C. difficile "likely represents infection" but not colonization. They explain that they expect milder symptoms in the youngest cases if they were only colonized. Is this reasonable?

One could counterargue that in the absence of testing for the most common diarrheagenic pathogen in the United States (norovirus), that diarrhea in at least some of these C. difficile–positive children was likely caused by undetected norovirus. That could partially explain why symptoms were not significantly different by age. One viral coinfection in nearly 500 diarrhea stools (even preselected by C. difficile positivity) seems low. Even if norovirus is not the wildcard here, the similar "disease" at all ages could suggest that something other than C. difficile is the cause. Norovirus and other viral agents testing of samples that were cultured for C. difficile could increase understanding of coinfection rates. Another issue is that 28% of C. difficile children did not have diarrhea, raising concern that these were colonized children.

The authors state that high antibiotic use (73% in phone interviewees) might have contributed to the high C. difficile detection rates. This seems logical, but the phone-derived data came from only about 8% of the total population. The original charted data from the entire population showed 33% antibiotic use. The charted data may have been more reliable because it was collected at the time of the C. difficile–positive stool, not 3-6 months later. Nevertheless, it seems apparent that common outpatient antibiotics could be a factor. If the data were compared with antibiotic use rates for C. difficile–negative children of the same ages, the conclusion would be more powerful.

Children less than 1year of age were not included because up to 73% (Eur. J. Clin. Microbiol. Infect. Dis. 1989;8:390-3) of infants have been reported as asymptomatically colonized. In similar studies, colonized infants were frequent (25% between 6 days and 6 months) up to about 3 years of age when rates dropped off to less than 3%, similar to adults. Inclusion of children in the second and third year of life likely means that not all detections were infections. But there is no way to definitively distinguish infection from colonization in this study.

A further step in filling the knowledge gap on C. difficile would be prospective surveillance with improved definitions of infection vs. colonization and a more complete search for potential concurrent causes of diarrhea. Undoubtedly, many of these C. difficile–positive children had true infection, but it also seems likely that some were colonized, particularly in the second and third year of life. It would be interesting to compare results from healthy controls vs. those with diarrhea using new multiplex molecular assays to gain a better understanding of what proportion of all children have detectable C. difficile with and without other pathogens.

Bottom line

NAP1 C. difficile is emerging in children. C. difficile detection, whether infected or colonized, in this many children is new. These data suggest that our best contributions to reducing the spread of C. difficile are the use of amoxicillin without clavulanate as first line – if antibiotics are needed for acute otitis media and for acute sinusitis – while we refrain from antibiotics for viral upper respiratory infections. As the old knight told Indiana Jones, "Choose wisely."

Factors associated with C. difficile detection in children

1. White race. Question more frequent health care and antibiotic exposure.

2. Age 12 to 23 months. Question whether the population is mix of colonized and infected children. This needs more study.

3. Amoxicillin/clavulanate or oral cephalosporin use for common outpatient infection. Is narrower spectrum, amoxicillin alone better?

4. A recent outpatient health care visit may be a cofactor with #1 and #3.

Dr. Harrison is professor of pediatrics and pediatric infectious diseases at Children’s Mercy Hospitals and Clinics, Kansas City, Mo. Dr. Harrison said he has no relevant financial disclosures. E-mail him at [email protected].