In 2010, the Emerging Infections Program (EIP) conducted active population-based CDI surveillance in select counties in 8 US states: California, Colorado, Connecticut, Georgia, Minnesota, New York, Oregon, and Tennessee. In 2011, the surveillance expanded to Maryland and New Mexico. The population of children aged 1 to 17 years across the EIP sites in 2010 and 2011 was 1 940 194 and 2 462 433, respectively.¹⁰ The surveillance methods have been described elsewhere.¹¹ Briefly, surveillance staff at each EIP site identified all positive C difficile test results either by toxin or molecular assay from all laboratories serving surveillance area residents. A pediatric CDI case was defined as a C difficile–positive stool specimen in a surveillance area resident aged 1 to 17 years who did not have a positive assay in the previous 8 weeks. Infants <12 months of age were excluded from surveillance. For each CDI case, medical records were reviewed to determine if the infection was health care facility–onset (HCFO; ie, positive stool collected >3 calendar days after admission) or community-onset (all others).¹² Community-onset CDI cases were further classified into 2 mutually exclusive groups: (1) community-onset, health care facility–associated (CO-HCFA) if there was a recent (ie, within 12 weeks before stool collection date) overnight stay in a health care facility or (2) community-associated (CA) if no recent overnight stay in a health care facility was documented. Data on clinical presentation, disease severity, clinical outcomes, medication exposures in the 2 weeks before stool collection, and underlying medical conditions were obtained from the medical records for all CDI cases. A 2-week instead of a 12-week period was used for medication exposure during the medical record review for operational purposes. However, the highest risk period for CDI is reported to be within 2 weeks of antibiotic cessation.¹³ Information on other enteric pathogens tested on the same day as the positive C difficile specimen was collected. Stool collection and testing for C difficile or other enteric pathogens was based on provider discretion.

A convenience sample of CA CDI cases with stool collected from January 1, 2010, to December 31, 2011, were contacted for a telephone interview within 3 to 6 months after stool collection. Persons aged 13 to 17 years were interviewed directly, whereas a parent or legal guardian was interviewed for children 1 to 12 years of age. Interviewees were asked additional questions regarding the CDI case’s clinical symptoms, medical history, exposures to outpatient health care settings, medications in the 12 weeks before stool collection, indication for taking antibiotics, and household exposures.

A separate convenience sample of C difficile–positive stool specimens was cultured, and recovered isolates underwent pulsed-field gel electrophoresis. Pulsed-field gel electrophoresis patterns were analyzed by using Bio-Numerics version 5.10 (Applied Maths, Austin, TX) and grouped into pulsed-field types by using Dice/UPGMA clustering, and an 80% similarity threshold was used to assign NAP types.¹⁴

This project was approved by the institutional review boards at the Centers for Disease Control and Prevention and participating sites. Verbal consent or assent, when appropriate, was obtained from all persons interviewed.

The total 2010 and 2011 US population census of children aged 1 to 17 years from surveillance areas was used to calculate incidence rates per 100 000 children across the 2 calendar years. Cases were stratified into ages 1 year, 2 to 3 years, 4 to 9 years, and 10 to 17 years. Missing race data (37%) were statistically imputed on the basis of the distribution of known race by age, gender, and surveillance site.

The proportion of cases diagnosed by NAATwas estimated by using data from annual laboratory practices surveys conducted among clinical, reference, and commercial laboratories serving the surveillance areas.

Demographic, exposure, and clinical characteristics and type of C difficile–positive diagnostic assay were compared by using χ² or Fisher’s exact tests to detect any difference across the 4 age groups. The Wilcoxon rank sum test was used to compare continuous variables. All analyses were conducted by using SAS version 9.2 (SAS Institute, Cary, NC).

During January 1, 2010, to December 31, 2011, 944 cases of pediatric CDI were identified among 885 children. There was no difference in the incidence of CDI between boys and girls, but the incidence was highest among white children and those aged 1 year old (ie, 12–23 months old) (Table 1). The incidence decreased between ages 1 to 6 years from 66.3 to 13.8 per 100 000 children and increased between ages 13 to 17 years from 8.8 to 25.6 per 100 000 children (Fig 1). Of the 944 cases identified, 667 (71%) were CA, 163 (17%) were CO-HCFA, and 114 (12%) were HCFO. In every age group, >50% of cases were CA (Fig 2).

The estimated proportion of cases detected by NAAT was not different across the age groups (Table 2). Presenting signs and symptoms were mild and similar across the age groups. Within 1 day of stool collection, diarrhea and a white blood cell (WBC) count of ≥ 15 000 cells per mm³ was documented in 680 (72%) and 68 (7%) of cases, respectively; 3 cases had radiographic evidence of ileus and 5 cases developed pseudomembranous colitis within 5 days of stool collection. Recurrence, defined as C difficile–positive stool within 2 to 8 weeks after previously positive stool, was documented in 100 (11%) cases overall, but it was less frequent among cases aged 10 to 17 years (P = .04) than in cases in other age groups.

The proportion of cases with severe disease, defined by abnormal radiographic finding (ileus or toxic megacolon), WBC count of ≥ 15 000 cells per mm³, pseudomembranous colitis, or ICU admission, was low (76; 8%) and similar across the age groups (P = .08) (Table 2). Underlying medical conditions were more frequently documented for cases aged 10 to 17 years (P < .001), particularly inflammatory bowel disease (P = .004). In most cases (830; 88%), C difficile–positive stool was collected as an outpatient, but the proportion of C difficile–positive stool collected as outpatient was significantly lower among cases aged 10 to 17 years compared with cases in other age groups (P = .005); cases aged 10 to 17 years were also more likely to be hospitalized within 7 days of stool collection (P = .004). Six cases overall required ICU admission, 1 case required colectomy, and there were no deaths.

Antibiotic use during the 14 days before C difficile–positive stool collection was documented in 33% of cases and did not differ across the age groups (P = .23). Among cases that used antibiotics, cephalosporins (131; 41%) and β-lactam agents with increased activity (98; 31%) were most commonly documented; a combination of amoxicillin and clavulanate (92; 94%) was the most common β-lactam with increased activity. The use of gastric acid suppressors, systemic steroids, chemotherapy, or other immunosuppressive therapies was not common and did not differ across the age groups.

Coinfection with another enteric pathogen was identified in 17 (3%) of 535 cases. The identified copathogens were bacterial (n = 12), protozoal (n = 4), and viral (n = 1) (Table 2). Evidence of coinfection was more common among children aged 2 to 9 years than among children in other age groups (P = .03). Compared with 518 cases who did not have coinfection identified, the coinfected cases were similar with respect to hospitalization (19% vs 29%; P = .34) and disease severity (9% vs 18%; P = .19).

C difficile was recovered from 132 (78%) of 169 positive specimens cultured; age distribution did not differ between culture-positive and culture-negative cases (P = .4). The 2 HCFO cases with C difficile isolates available were combined with the 29 CO-HCFA cases to assess differences in strain distribution between health care–associated and CA cases. NAP1 was the most common strain (30; 23%) followed by NAP11 (17; 13%) and NAP4 (15; 11%) (Table 3). There was no difference in the proportion of CA and health care–associated cases that were NAP1 (22% vs 26%; P = .63). Four cases were NAP7 or NAP8, and all were CA.

Of 667 CA CDI cases, 123 (18%) were contacted for health interviews; 95 (77%) completed interviews, 15 (12%) could not be contacted, and 13 (11%) declined participation. Among 95 patients interviewed, 84 (88%) reported diarrhea on the day of stool collection and were included in the analyses. The 84 included cases were similar to the CACDI cases not interviewed with regard to age and gender, but interviewed cases were more likely to be white (93% vs 64%; P<.0001).

Of the 84 cases included, 61 (73%) reported antibiotic use during the 12 weeks before diarrhea onset, and the most commonly reported reason for antimicrobial therapy was for ear, sinus, or upper respiratory tract infection (51; 84%) (Table 4). Penicillins (27; 44%) were the most commonly reported antibiotics used, followed by cephalosporins (24; 39%) and β-lactams with increased activity (16; 26%). The use of gastric acid suppressors (proton pump inhibitors or histamine₂-receptor blockers) was not common (8; 9%). Among 73 (87%) cases who reported any outpatient health care exposures during the 12 weeks before diarrhea onset, a doctor’s office visit was the most common (71; 97%), followed by a dental office visit (23; 32%). Only 7 (8%) cases had neither outpatient health care nor antibiotic exposure.

Among 19 (23%) cases exposed to household members with diarrhea, 3 reported exposure to a household member with confirmed CDI. Fourteen (17%) and 12 (14%) cases reported exposure to household members who worked in health care facilities and to infants, respectively.