Journal Article

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

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

2019

Overview

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. 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Anti-Bacterial Agents - therapeutic use / Antibiotics / Antimicrobial resistance / Arm circumference / Bacterial diseases / Bacterial infections / Biology and Life Sciences / Breathing / Care and treatment / Caregivers / Child health / Child, Preschool / Children / Children & youth / Clinical Decision-Making / Clinical trials / Confidence intervals / Decision analysis / Decision making / Diagnosis / Discrimination / Disease Progression / Double-Blind Method / Drug resistance / Enrollments / Failure / Family / Female / Health risks / Health services / Heart rate / HIV / Hospitals / Human immunodeficiency virus / Humans / Infant / Infection / Linear Models / Malaria / Malawi / Male / Medical prognosis / Medical research / Medical treatment / Medicine and Health Sciences / Microbial drug resistance / Models, Theoretical / Mortality / Multivariate Analysis / Pediatrics / Pneumonia / Pneumonia - drug therapy / Practice guidelines (Medicine) / Prospective Studies / Public health / Randomization / Recurrence (Disease) / Regression analysis / Regression models / Respiration / Risk / Risk Assessment / Risk factors / Secondary analysis / Statistical analysis / Streptococcus infections / Treatment Failure / Vaccines / Vector-borne diseases / World Health Organization