Optimising Antibiotic Use for Young African Children Hospitalised With Lower Respiratory Tract Infections: the Role of Biomarkers, Clinical Severity Scoring and Clinician Attitudes

Antimicrobial resistance (AMR) has emerged as one of the most pressing global health threats and is driven largely by the inappropriate use of antibiotics. Strengthening antibiotic stewardship is therefore a critical public health priority to slow the emergence of resistant pathogens and preserve the effectiveness of existing therapies. Stewardship in inherently complex, particularly in the management of lower respiratory tract infections (LRTIs) in children. Optimising appropriate antibiotic use requires good clinical acumen, diagnostic accuracy, and sound clinical decision-making. This decision-making is influenced by multiple environmental, social, behavioural and psychological factors.

LRTIs remain a leading cause of mortality and morbidity in children under five years of age, particularly in low- and middle-income countries (LMICs). Despite progress in pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine coverage, LRTIs continue to account for a significant proportion of paediatric hospital admissions and deaths. There has been a marked shift in the aetiology of LRTIs over the last two decades, with a now greater proportion of LRTIs attributable to respiratory viruses and a reduced proportion caused by bacterial infections. Data from The Pneumonia Etiology Research for Child Health (PERCH) study demonstrated that viruses accounted for approximately two-thirds of childhood pneumonia cases, while bacteria accounted for approximately one-quarter.

The World Health Organisation (WHO) pneumonia case definition is intentionally highly sensitive in order to reduce mortality, particularly in resource-limited settings. Importantly, the WHO definition does not differentiate between viral, bacterial or mixed aetiology LRTI. Consequently, many children fulfilling the criteria for severe pneumonia receive antibiotic treatment despite the predominance of viral causes. This challenge is particularly relevant in infants and young children where bronchiolitis and bronchopneumonia frequently present with overlapping clinical features and are often difficult to distinguish clinically.

Although bronchiolitis is generally managed with supportive care alone and bronchopneumonia is treated with antibiotics, clinicians frequently struggle to differentiate between these two conditions, resulting in over-prescribing of antibiotics. Diagnostic uncertainty, concerns regarding clinical deterioration, fear of missing serious bacterial infection, and limitations in available diagnostic tools all contribute to antibiotic prescribing decisions. While this approach may reduce the risk of undertreatment, it also contributes to unnecessary antibiotic exposure, increased healthcare costs, adverse drug effects, disruptions of the microbiome, and the development of antimicrobial resistance.

Clinical severity assessment tools may help identify children at higher risk of adverse outcomes. The Pneumonia Research Partnership to Assess WHO Recommendations (PREPARE) clinical severity score was derived from data obtained from more than 20 countries and has demonstrated good external validity in predicting pneumonia-related mortality among children aged 2-59 months hospitalised with pneumonia. The PREPARE score incorporates patient age, sex, weight-for-age z-score, body temperature, respiratory rate, level of consciousness, cyanosis, and oxygen saturation to produce a risk score that can assist with clinical risk stratification.