It Takes Two to Tango: Impact of a Reverse Two-Step Algorithm for Clostridioides difficile Infection Diagnosis in Pediatric Oncology and Hematopoietic Cell Transplant Populations

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ID: 327350
2026
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Abstract
Abstract Background Implementation of a reverse two-step algorithm (RTSA) for diagnosing C. difficile infection (CDI) in the adult population has improved diagnostic accuracy and reduced CDI-directed antibiotic exposure. The impact of the RTSA in pediatric CDI is unknown. This study aimed to evaluate the impact of RTSA implementation on CDI rates, anti-C. difficile antibiotic exposure, and clinical outcomes among hospitalized pediatric oncology and hematopoietic stem cell transplantation (HCT) patients. Methods In June 2024, our institution implemented a RTSA, which included a nucleic acid amplification test (NAAT) followed by a reflex enzyme immunoassay (EIA) for CDI diagnosis. We conducted a retrospective chart review comparing the pre-implementation (1/2023 – 5/2024) and post-implementation (6/2024 – 9/2025) periods (Figure 1). We included hospitalized patients (2-18 years of age) receiving chemotherapy or HCT in oncology inpatient units who developed diarrhea on or after admission and tested positive for C. difficile by Biofire® Filmarray® Gastrointestinal Panel (GIP) or nucleic acid amplification test (NAAT). Cases were identified through institutional epidemiology surveillance and classified as CDI or non-CDI according to the National Healthcare Safety Network (NHSN) definitions. Demographic data, laboratory findings, including CDI testing results, anti-C. difficile therapy, and clinical outcomes at 8 weeks were collected. P-values < 0.05 were considered statistically significant. Results Among 104 C. difficile-positive stools (by either GIP or NAAT) from 70 patients, 82 (78.8%) episodes met CDI criteria per NHSN. The median age was 9.7 years (IQR, 5.2-14.7), with a male predominance (56%), and most had hematological malignancies (54%). The percentage of tests yielding a CDI diagnosis decreased from 96% in the pre-implementation period to 46% in the post-implementation period (Figure 1, p < 0.0001), with a corresponding decline in overall CDI rates from 4.4 to 1.1 cases per 1,000 patient-days. Healthcare-onset CDI (HO-CDI) demonstrated a similar decrease in rate in post-implementation period (1.9 to 0.6 cases per 1,000 patient-days). Concordantly, anti-C. difficile antibiotic exposure decreased following RTSA implementation (45.2 days to 15.5 days of therapy per 1,000 patient-days). No CDI-related deaths occurred during either period. Among patients with NAAT-positive/EIA-negative results who were not treated, no adverse outcomes, including recurrence, progression to severe CDI, or CDI-related mortality, were observed within 8 weeks. Conclusion Among hospitalized pediatric oncology and HCT patients, implementation of the RTSA significantly reduced overall inpatient CDI rates and antibiotic utilization without evidence of adverse clinical outcomes.
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Authors
Journal journal of the pediatric infectious diseases society
Year 2026
DOI
10.1093/jpids/piag070/piag070.070
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