Discussion

Updated clinical practice guidelines for CDI were recently endorsed by the IDSA and the Society for Healthcare Epidemiology of America (SHEA).Reference McDonald, Gerding and Johnson⁴ Compared to the previous 2010 guideline, the updated document included clinical practice guidance for pediatric populations. Although the guideline authors acknowledged the benefits and drawbacks of both toxin EIAs and NAATs, a single test was not wholly endorsed. NAATs (alone or as part of a multistep algorithm) were recommended only if the hospital had pre-agreed criteria for submitting stool specimens for C. difficile testing. The purpose of these prearranged criteria is to limit C. difficile testing in patients with low likelihood of CDI and avoid detection of asymptomatic carriage. In institutions without pre-agreed criteria for submitting stool specimens for C. difficile testing, stool toxin testing as part of a multistep algorithm was recommended. These survey data, gathered shortly before publication of the updated IDSA/SHEA guidelines,Reference McDonald, Gerding and Johnson⁴ provide information about the prevalence of CDI diagnostic practices in the United States as it relates to limiting detection of asymptomatic carriage in children. Thus, these data inform opportunities for improving C. difficile diagnostic stewardship, particularly among institutions utilizing NAATs for C. difficile diagnosis, in accordance with the recently updated guidelines. Because adoption of diagnostic stewardship practices is not associated with various hospital characteristics (eg, freestanding children’s hospital, hospital size or university affiliation), our data suggest that need for diagnostic stewardship practices is a relatively pervasive issue.

These data suggest that many PID physicians have an opportunity to advocate for institutional changes to C. difficile diagnostic testing practices that may reduce the misdiagnosis of CDI in asymptomatic carriers. Although routine testing for asymptomatic carriage is exceedingly uncommon, certain diagnostic stewardship practices, particularly IDSA/SHEA-endorsed age-based restrictions of testing, were reported by only half of respondents, irrespective of whether or not toxin or NAAT testing was being used in their institution. In addition, roughly one-third of respondents reported the use of a multiplex PCR to diagnose CDI, and nearly three-quarters reported that results were provided even if they were not requested by the clinician. Thus, these data suggest that asymptomatic carriage is likely commonly detected, particularly in patients in whom toxin testing is not performed.

Because antibiotics are not generally indicated for asymptomatic carriage, misdiagnosis of carriage as CDI leads to unnecessary antibiotic exposure. The antibiotic stewardship implications of judicious use of C. difficile testing are highlighted in this survey by responses regarding management of NICU patients tested for C. difficile. Despite strong evidence that C. difficile does not cause infection in neonatesReference Tamma and Sandora⁵ and American Academy of PediatricsReference Schutze and Willoughby⁶ (AAP) guidelines discouraging testing in this age group, roughly half of respondents who reported testing NICU patients for C. difficile provide treatment for CDI. The AAP-endorsed age-based restrictions of C. difficile testing were adopted by the updated IDSA/SHEA guideline.Reference McDonald, Gerding and Johnson⁴ Age-based testing restrictions, the uptake of which may be improved with electronic order entry messaging,Reference Kociolek, Bovee and Carter^7, Reference Nicholson, Freswick and Di Pentima⁸ may improve testing decisions and reduce unnecessary antibiotic therapy for C. difficile carriage, leading to reduced healthcare costs.Reference Kociolek, Bovee and Carter^7, Reference Truong, Gombar and Wilson⁹ However, reducing unnecessary testing in older children may be more challenging. Although the vast majority of respondents report that C. difficile testing is restricted for formed stools submitted to the laboratory, this does not prevent testing in children with clinically insignificant diarrhea (ie, 2 or fewer unformed stools in 24 hours) or diarrhea in patients who are unlikely to have CDI. In these cases, pediatric healthcare provider educationReference Kociolek, Bovee and Carter⁷ and/or leveraging the electronic health recordReference Truong, Gombar and Wilson⁹ to monitor frequency of diarrhea and recent laxative use may be effective. Notably, although this definition of clinically significant diarrhea has not been validated in children, this definition is recommended in the AAP CDI clinical care guidelines.Reference McDonald, Gerding and Johnson⁴

In addition to the antibiotic stewardship implications of CDI misdiagnosis, there are also other consequences. For example, misattribution of diarrheal symptoms to C. difficile may delay identification of the true diarrheal etiology, potentially leading to worse outcomes. We have observed diarrheal symptoms caused by conditions such as typhlitis, ulcerative colitis, and toxic shock syndrome initially mistakenly attributed to CDI because of positive tcdB PCR in these patients. Furthermore, CDI misdiagnosis leads to overestimation of hospital CDI rates, impairing accurate institutional CDI surveillance and limiting reliable interfacility comparisons of CDI rates. Healthcare-associated infection rates are an important hospital quality metric, and implementation and monitoring the impact of CDI prevention initiatives require accurate surveillance. The impact of overestimation of CDI rates may be even higher in populations at high risk for C. difficile carriage, such as hospitalized childrenReference Leibowitz, Soma, Rosen, Ginocchio and Rubin¹⁰ and children with cancer.Reference Dominguez, Dolan and West¹¹ Furthermore, with the potential for hospital nonreimbursement for healthcare-associated infections such as CDI, hospitals have a financial incentive for accurately measuring and avoiding overestimation of CDI rates.Reference Fong, Fatica and Hall¹² These consequences highlight the importance of developing diagnostic testing methods that reliably distinguish carriage and CDI, which has been a difficult task.Reference Kociolek² Until that happens, diagnostic stewardship will remain an important strategy for optimizing utilization of C. difficile diagnostic testing.

Our study has some limitations. Although our 57% physician response rate was relatively high, and respondents are similar to nonrespondents regarding all practice variables examined, a response bias may still exist. Testing practices may have differed between respondents and non-respondents. Physicians elect to join the EIN, and this convenience sample may not be generalizable to all pediatric infectious diseases physicians. In addition, although respondents reported the prevalence of policies, hospital and provider compliance with these strategies could not be determined.

In summary, these data suggest that there are pervasive opportunities to improve CDI diagnostic stewardship practices in children and to develop institutional policies to align with recently updated IDSA/SHEA guidance, particularly in hospitals using NAATs alone for CDI diagnosis in children. However, even with implementation of these IDSA/SHEA-endorsed practices, provider education remains an essential component of diagnostic stewardship to assist providers in appropriately selecting patients for C. difficile testing. Future work should identify cost-effective, scalable, and sustainable strategies for CDI diagnostic stewardship.