The management of patients at risk for a low-frequency but serious illness poses many challenges for health professionals. Neonatal early-onset sepsis (EOS) in late-preterm and term neonates is a classic example of such a low-frequency serious condition. Faced with the possibility that such an infant, even if well appearing, can develop EOS, clinicians have traditionally erred on the side of treating with antibiotics until the EOS is ruled out by some combination of a continued normal clinical examination, negative blood cultures, and negative rapid diagnostic test results. A liberal antibiotic treatment strategy resulted in a large number (as high as several hundreds) of infants being needlessly treated with antibiotics for every neonate with true EOS. This strategy has been relatively easy for clinicians to follow because the burden of administering a short course of antibiotics is relatively low, and the adverse effects of antibiotics (eg, emergence of antibiotic resistance, altered...

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