Background Pneumonia causes significant morbidity and mortality in children worldwide, especially in resource-poor settings. Accurate identification of bacterial etiology leads to timely antibiotic initiation, minimizing overuse, and development of resistance. Host biomarkers may improve diagnostic sensitivity and specificity. We assessed the ability of biomarkers to correctly identify bacterial pneumonia in children who present with respiratory distress. Methods A librarian-directed search was conducted of MEDLINE, EMBASE, CENTRAL, Global Health, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to May 2020 with no language restriction. Included studies compared a diagnostic biomarker in children with bacterial pneumonia to those with nonbacterial respiratory distress. Results There were 31 observational studies of 23 different biomarkers. C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were the biomarkers with sufficient data for meta-analysis. Meta-analysis revealed that CRP and PCT best differentiated bacterial from viral pneumonia with CRP summary AUROC (area under the receiver operating characteristic curve) 0.71 (0.69-0.73), Youden index 53 mg/L, sensitivity 0.70 (0.68-0.78), and specificity 0.64 (0.58-0.68) and PCT summary AUROC 0.70 (0.67-0.74), Youden index 0.59 ng/mL, sensitivity 0.69 (0.65-0.77), and specificity 0.64 (0.60-0.68). WBC and ESR did not perform as well. Nineteen other inflammatory and immunologic biomarkers were identified including CRP/mean platelet value, neutrophil/leukocyte ratio, interleukin 6, and interferon-alpha, with sensitivities from 60% to 85% and specificities from 76% to 83%. Conclusion CRP and PCT performed better than WBC and ESR but had suboptimal sensitivity. Some less well-studied novel biomarkers appear to have promise particularly in combination.

Globally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4-20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a chest x-ray abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8-3.6) mmol/L among children who survived versus 7.2 (2.6-9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% confidence interval: 0.69-0.87, P £ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0-4.0, and > 4.0 mmol/L accurately riskstratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.