Developing a clinical prediction model to modify empirical antibiotics for non-typhoidal Salmonella bloodstream infection in children under-five in the Democratic Republic of Congo

BACKGROUND: Non-typhoidal Salmonella (NTS) frequently cause bloodstream infection in children under-five in sub-Saharan Africa, particularly in malaria-endemic areas. Due to increasing drug resistance, NTS are often not covered by standard-of-care empirical antibiotics for severe febrile illness. We developed a clinical prediction model to orient the choice of empirical antibiotics (standard-of-care versus alternative antibiotics) for children admitted to hospital in settings with high proportions of drug-resistant NTS.

METHODS: Data were collected during a prospective cohort study in children (> 28 days-< 5 years) admitted with severe febrile illness to Kisantu district hospital, DR Congo. The outcome variable was blood culture confirmed NTS bloodstream infection; the comparison group were children without NTS bloodstream infection. Predictors were selected a priori based on systematic literature review. The prediction model was developed with multivariable logistic regression; a simplified scoring system was derived. Internal validation to estimate optimism-corrected performance was performed using bootstrapping and net benefits were calculated to evaluate clinical usefulness.

RESULTS: NTS bloodstream infection was diagnosed in 12.7% (295/2327) of enrolled children. The area under the curve was 0.79 (95%CI: 0.76-0.82) for the prediction model, and 0.78 (0.85-0.80) for the scoring system. The estimated calibration slopes were 0.95 (model) and 0.91 (scoring system). At a decision threshold of 20% NTS risk, the prediction model and scoring system had 57% and 53% sensitivity, and 85% specificity. The net benefit for decisions thresholds < 30% ranged from 2.4 to 3.9 per 100 children.

CONCLUSION: The model predicts NTS bloodstream infection and can support the choice of empiric antibiotics to include coverage of drug-resistant NTS, in particular for decision thresholds < 30%. External validation studies are needed to investigate generalizability.

TRIAL REGISTRATION: DeNTS study, clinicaltrials.gov: NCT04473768 (registration 16/07/2020) and TreNTS study, clinicaltrials.gov: NCT04850677 (registration 20/04/2021).