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
Abstract 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 ill...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12879-024-10319-x |
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| author | Bieke Tack Daniel Vita Jules Mbuyamba Emmanuel Ntangu Hornela Vuvu Immaculée Kahindo Japhet Ngina Aimée Luyindula Naomie Nama Tito Mputu Justin Im Hyonjin Jeon Florian Marks Jaan Toelen Octavie Lunguya Jan Jacobs Ben Van Calster |
| author_facet | Bieke Tack Daniel Vita Jules Mbuyamba Emmanuel Ntangu Hornela Vuvu Immaculée Kahindo Japhet Ngina Aimée Luyindula Naomie Nama Tito Mputu Justin Im Hyonjin Jeon Florian Marks Jaan Toelen Octavie Lunguya Jan Jacobs Ben Van Calster |
| author_sort | Bieke Tack |
| collection | DOAJ |
| description | Abstract 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). |
| format | Article |
| id | doaj-art-0f81d4844daf442297e7902b5a900e5e |
| institution | Kabale University |
| issn | 1471-2334 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Infectious Diseases |
| spelling | doaj-art-0f81d4844daf442297e7902b5a900e5e2025-02-02T12:10:50ZengBMCBMC Infectious Diseases1471-23342025-01-0125111410.1186/s12879-024-10319-xDeveloping a clinical prediction model to modify empirical antibiotics for non-typhoidal Salmonella bloodstream infection in children under-five in the Democratic Republic of CongoBieke Tack0Daniel Vita1Jules Mbuyamba2Emmanuel Ntangu3Hornela Vuvu4Immaculée Kahindo5Japhet Ngina6Aimée Luyindula7Naomie Nama8Tito Mputu9Justin Im10Hyonjin Jeon11Florian Marks12Jaan Toelen13Octavie Lunguya14Jan Jacobs15Ben Van Calster16Department of Clinical Sciences, Institute of Tropical MedicineSaint Luc Hôpital Général de Référence KisantuDepartment of Microbiology, Institut National de Recherche BiomédicaleSaint Luc Hôpital Général de Référence KisantuSaint Luc Hôpital Général de Référence KisantuDepartment of Microbiology, Institut National de Recherche BiomédicaleSaint Luc Hôpital Général de Référence KisantuSaint Luc Hôpital Général de Référence KisantuSaint Luc Hôpital Général de Référence KisantuSaint Luc Hôpital Général de Référence KisantuInternational Vaccine InstituteInternational Vaccine InstituteInternational Vaccine InstituteDepartment of Pediatrics, University Hospitals LeuvenDepartment of Microbiology, Institut National de Recherche BiomédicaleDepartment of Clinical Sciences, Institute of Tropical MedicineDepartment of Development and Regeneration, KU LeuvenAbstract 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).https://doi.org/10.1186/s12879-024-10319-xNon-typhoidal SalmonellaBloodstream infectionChildren under-fiveClinical prediction modelEmpirical antibiotics |
| spellingShingle | Bieke Tack Daniel Vita Jules Mbuyamba Emmanuel Ntangu Hornela Vuvu Immaculée Kahindo Japhet Ngina Aimée Luyindula Naomie Nama Tito Mputu Justin Im Hyonjin Jeon Florian Marks Jaan Toelen Octavie Lunguya Jan Jacobs Ben Van Calster 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 BMC Infectious Diseases Non-typhoidal Salmonella Bloodstream infection Children under-five Clinical prediction model Empirical antibiotics |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Non-typhoidal Salmonella Bloodstream infection Children under-five Clinical prediction model Empirical antibiotics |
| url | https://doi.org/10.1186/s12879-024-10319-x |
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