Development of a prognostic risk score to aid antibiotic decision-making for children aged 2-59 months with World Health Organization fast breathing pneumonia in Malawi

An Innovative Treatments in Pneumonia (ITIP) secondary analysis

Eric McCollum, Siobhan P. Brown, Evangelyn Nkwopara, Tisungane Mvalo, Susanne May, Amy Sarah Ginsburg

Research output: Contribution to journalArticle

Abstract

Background Due to increasing antimicrobial resistance in low-resource settings, strategies to rationalize antibiotic treatment of children unlikely to have a bacterial infection are needed. This study’s objective was to utilize a database of placebo treated Malawian children with World Health Organization (WHO) fast breathing pneumonia to develop a prognostic risk score that could aid antibiotic decision making. Methods We conducted a secondary analysis of children randomized to the placebo group of the Innovative Treatments in Pneumonia (ITIP) fast breathing randomized, controlled, noninferiority trial. Participants were low-risk HIV-uninfected children 2–59 months old with WHO fast breathing pneumonia in Lilongwe, Malawi. Study endpoints were treatment failure, defined as either disease progression at any time on or before Day 4 of treatment or disease persistence on Day 4, or relapse, considered as the recurrence of pneumonia or severe disease among previously cured children between Days 5 and 14. We utilized multivariable linear regression and stepwise model selection to develop a model to predict the probability of treatment failure or relapse. Results Treatment failure or relapse occurred in 11.5% (61/526) of children included in this analysis. The final model incorporated the following predictors: heart rate terms, mid-upper arm circumference, malaria status, water source, family income, and whether or not a sibling or other child in the household received childcare outside the home. The model’s area under the receiver operating characteristic score was 0.712 (95% confidence interval 0.66, 0.78) and it explained 6.1% of the variability in predicting treatment failure or relapse (R2, 0.061). For the model to categorize all children with treatment failure or relapse correctly, 77% of children without treatment failure or relapse would require antibiotics. Conclusion The model had inadequate discrimination to be appropriate for clinical application. Different strategies will likely be required for models to perform accurately among similar pediatric populations.

Original languageEnglish (US)
Article numbere0214583
JournalPloS one
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2019

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Malawi
World Health Organization
pneumonia
breathing
decision making
Pneumonia
Decision Making
Respiration
Decision making
antibiotics
relapse
Health
Anti-Bacterial Agents
Treatment Failure
Recurrence
Therapeutics
placebos
Pediatrics
Placebos
child care

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Development of a prognostic risk score to aid antibiotic decision-making for children aged 2-59 months with World Health Organization fast breathing pneumonia in Malawi : An Innovative Treatments in Pneumonia (ITIP) secondary analysis. / McCollum, Eric; Brown, Siobhan P.; Nkwopara, Evangelyn; Mvalo, Tisungane; May, Susanne; Ginsburg, Amy Sarah.

In: PloS one, Vol. 14, No. 6, e0214583, 01.06.2019.

Research output: Contribution to journalArticle

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abstract = "Background Due to increasing antimicrobial resistance in low-resource settings, strategies to rationalize antibiotic treatment of children unlikely to have a bacterial infection are needed. This study’s objective was to utilize a database of placebo treated Malawian children with World Health Organization (WHO) fast breathing pneumonia to develop a prognostic risk score that could aid antibiotic decision making. Methods We conducted a secondary analysis of children randomized to the placebo group of the Innovative Treatments in Pneumonia (ITIP) fast breathing randomized, controlled, noninferiority trial. Participants were low-risk HIV-uninfected children 2–59 months old with WHO fast breathing pneumonia in Lilongwe, Malawi. Study endpoints were treatment failure, defined as either disease progression at any time on or before Day 4 of treatment or disease persistence on Day 4, or relapse, considered as the recurrence of pneumonia or severe disease among previously cured children between Days 5 and 14. We utilized multivariable linear regression and stepwise model selection to develop a model to predict the probability of treatment failure or relapse. Results Treatment failure or relapse occurred in 11.5{\%} (61/526) of children included in this analysis. The final model incorporated the following predictors: heart rate terms, mid-upper arm circumference, malaria status, water source, family income, and whether or not a sibling or other child in the household received childcare outside the home. The model’s area under the receiver operating characteristic score was 0.712 (95{\%} confidence interval 0.66, 0.78) and it explained 6.1{\%} of the variability in predicting treatment failure or relapse (R2, 0.061). For the model to categorize all children with treatment failure or relapse correctly, 77{\%} of children without treatment failure or relapse would require antibiotics. Conclusion The model had inadequate discrimination to be appropriate for clinical application. Different strategies will likely be required for models to perform accurately among similar pediatric populations.",
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