Remarks ■ The recommendation was based on four trials of 9823 infants aged 0–59 days in rural and semi-urban PHC facilities in five countries: Bangladesh, Democratic Republic of the Congo, Kenya, Nigeria and Pakistan. The trials all compared simplified regimens that included oral antibiotics (oral amoxicillin or cotrimoxazole) versus the comparator – WHO-recommended treatment of penicillin IM for 7 days plus gentamicin IM for 7 days. Four regimens were tested.― Regimen 1: oral cotrimoxazole for 7 days plus gentamicin IM/IV for 7 days― Regimen 2: procaine penicillin IM/IV plus gentamicin IM/IV for 2 days followed by oral amoxicillin for 5 days― Regimen 3: oral amoxicillin for 7 days plus gentamicin IM/IV for 2 days― Regimen 4: oral amoxicillin for 7 days plus gentamicin IM/IV for 7 days. ■ The GDG considered that regimen 1 may cause harm (increased mortality, treatment failure, adverse events) so did not recommend it. ■ The GDG considered that regimen 2 had no benefit over the comparator (penicillin plus gentamicin IM for 7 days) so did not recommend it. ■ The GDG considered that regimens 3 and 4 may improve critical outcomes when compared with penicillin plus gentamicin IM for 7 days (the comparator). The GDG noted that the evidence for both regimen 3 and 4 was low certainty: evidence for regimen 3 was available only from a single trial in Africa (Democratic Republic of the Congo, Kenya and Nigeria) while for regimen 4 data were available from three trials from both Asia and Africa (Bangladesh, Democratic Republic of the Congo, Kenya, Nigeria and Pakistan). ■ Thus, the GDG made a strong recommendation for regimen 4 and a conditional recommendation for regimen 3, meaning that if regimen 4 was not possible (i.e. if 7 days of gentamicin was not feasible), then regimen 3 may be considered (i.e. gentamicin for only 2 days). ■ The evidence for regimen 4 was judged to be of moderate certainty in the previous guideline and low certainty in this guideline. The evidence was considered to be low certainty as there was serious imprecision for treatment failure (RR 0.86, 95% CI: 0.72 to 1.02) and a serious risk of bias (substantial number of missing participants relative to outcome events in both arms of the study, and poor adherence by the parent to parental administration in the oral amoxicillin arm). ■ The GDG also emphasized that it was important to continue parenteral antibiotics for such a serious condition as septicaemia for at least 7 days where feasible. ■ The GDG made these recommendations recognizing that regimen 4 would have additional costs (e.g. the cost of the longer duration of antibiotics and additional staff time). ■ The GDG recognized that there were limited data on the dose of antibiotics. Based on the trials included in the evidence review, the GDG considered that the following antibiotic doses should be used: oral amoxicillin 50 mg/kg every 12 hours in the first week of life and every 8 hours after the first week of life for a total of at least 7 days plus gentamicin IM/IV 5 mg/kg once a day in the first week of life and 7.5 mg/kg once a day after the first week of life for a total of at least 7 days (regimen 4) or for 2 days if 7 days is not possible (regimen 3). ■ The GDG made a strong recommendation despite the limited evidence in non-hospital settings as they felt strongly about the importance of providing clear guidance for the management of unwell infants when referral to hospital is not possible. The GDG were able to use their knowledge and experience in best practice clinical management of sepsis in young infants to make this recommendation by consensus.