Oral amoxicillin for management of fast breathing or chest indrawing pneumonia without danger signs in children aged 2–59 months: a systematic review and meta-analysis

Abstract

Background World Health Organization (WHO) guidelines recommend oral amoxicillin as first-line therapy for pneumonia in children aged 2–59 months. However, uncertainty remains regarding its effectiveness compared with no antibiotics for fast breathing pneumonia and with injectable antibiotics for chest indrawing pneumonia without danger signs. Methods We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (January 2000–August 2024) for randomised and quasi-randomised trials without language restrictions. Eligible studies compared oral amoxicillin vs. no antibiotics for fast breathing pneumonia or outpatient oral amoxicillin vs. inpatient injectable antibiotics for chest indrawing pneumonia without danger signs in children (2–59 months). Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects model; certainty was assessed using GRADE. Results Four trials (n = 7,699) compared oral amoxicillin with no antibiotics for fast breathing pneumonia, and three (n = 4,864) compared oral with injectable antibiotics for chest indrawing pneumonia. For fast breathing pneumonia, oral amoxicillin reduced treatment failure by 16% at day 14 (RR = 0.84; 95% CI = 0.75, 0.94, I2 = 0%; moderate certainty). For chest indrawing pneumonia, treatment failure was similar between groups at day 6 (RR = 0.96; 95% CI = 0.83, 1.11) and day 14 (RR = 0.94; 95% CI = 0.79, 1.13), while mortality was 72% lower with oral amoxicillin (RR = 0.28; 95% CI = 0.09, 0.86). Serious adverse events did not differ between groups. Conclusions In children (2–59 months), oral amoxicillin significantly reduces treatment failure compared to no antibiotics for fast breathing pneumonia and is comparable to injectable antibiotics for chest indrawing pneumonia without danger signs. Notably, oral amoxicillin was associated with a 72% reduction in mortality compared with injectable antibiotics in children with chest-indrawing pneumonia, although absolute risk differences were small. These findings support its broader implementation as an accessible, programmatically feasible, and WHO-recommended option for pneumonia management in low-resource settings. Registration PROSPERO: CRD42023439851