Clinical Prediction Rule to Guide Diagnostic Testing for Shigellosis and Improve Antibiotic Stewardship for Pediatric Diarrhea

BACKGROUND: Diarrheal diseases are a leading cause of death for children aged <5 years. Identification of etiology helps guide pathogen-specific therapy, but availability of diagnostic testing is often limited in low-resource settings. Our goal is to develop a clinical prediction rule (CPR) to guide clinicians in identifying when to use a point-of-care (POC) diagnostic for Shigella in children presenting with acute diarrhea. METHODS: We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) study to build predictive models for diarrhea of Shigella etiology in children aged ≤59 months presenting with moderate to severe diarrhea in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using cross-validation. We used the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study to externally validate our GEMS-derived CPR. RESULTS: Of the 5011 cases analyzed, 1332 (27%) had diarrhea of Shigella etiology. Our CPR had high predictive ability (area under the receiver operating characteristic curve = 0.80 [95% confidence interval, .79–.81]) using the top 2 predictive variables, age and caregiver-reported bloody diarrhea. We show that by using our CPR to triage who receives diagnostic testing, 3 times more Shigella diarrhea cases would have been identified compared to current symptom-based guidelines, with only 27% of cases receiving a POC diagnostic test. CONCLUSIONS: We demonstrate how a CPR can be used to guide use of a POC diagnostic test for diarrhea management. Using our CPR, available diagnostic capacity can be optimized to improve appropriate antibiotic use.