Safety and efficacy of C-reactive protein-guided antibiotic use to treat acute respiratory infections in Tanzanian children: a planned subgroup analysis of a randomized, controlled non-inferiority trial evaluating a novel electronic clinical decision algorithm (ePOCT).

Background. The safety and efficacy of using C-reactive protein (CRP) to decide on antibiotic prescription among febrile children at risk of pneumonia has not been tested. Methods. This was a randomized (1:1) controlled noninferiority trial in 9 primary care centers in Tanzania (substudy of the ePOCT trial evaluating a novel electronic decision algorithm). Children aged 2-59 months with fever and cough and without life-threatening conditions received an antibiotic based on a CRP-informed strategy (combination of CRP >= 80 mg/L plus age/temperature-corrected tachypnea and/or chest indrawing) or current World Health Organization standard (respiratory rate >= 50 breaths/minute). The primary outcome was clinical failure by day (D) 7; the secondary outcomes were antibiotic prescription at D0, secondary hospitalization, or death by D30. Results. A total of 1726 children were included (intervention: 868, control: 858; 0.7% lost to follow-up). The proportion of clinical failure by D7 was 2.9% (25/865) in the intervention arm vs 4.8% (41/854) in the control arm (risk difference, -1.9% [95% confidence interval {CI}, -3.7% to -.1%]; risk ratio [RR], 0.60 [95% CI, .37-.98]). Twenty of 865 (2.3%) children in the intervention arm vs 345 of 854 (40.4%) in the control arm received antibiotics at D0 (RR, 0.06 [95% CI, .04-.09]). There were fewer secondary hospitalizations and deaths in the CRP arm: 0.5% (4/865) vs 1.5% (13/854) (RR, 0.30 [95% CI, .10-.93]). Conclusions. CRP testing using a cutoff of >= 80 mg/L, integrated into an electronic decision algorithm, was able to improve clinical outcome in children with respiratory infections while substantially reducing antibiotic prescription.