Table 1. Case definitions and management according to the WHO guideline [3] and study outcomes.

Case definitions	Recommendation		Management
Possible serious bacterial infection (PSBI): young infant with one or more of the following signs: not able to feed since birth or stopped feeding well or not feeding at all, convulsions, severe chest in-drawing, fever (temperature ≥ 38°C), low body temperature (< 35.5°C), movement only when stimulated or no movement at all, fast breathing (60 breaths per minute or more) in infants 0–59 days of age.	Refer to district hospital except those young infants with only fast breathing in 7–59 days of age		Give young infants 7–59 days of age pre-referral treatment (first dose ampicillin 50mg/kg or benzyl penicillin 50,000 units/kg and gentamicin injection 5–7.5mg/kg intramuscularly) as per WHO operational guidelines [6]—except in young infants with only fast breathing.
Re-categorize if referral not feasible
○ Fast breathing only in young infants less than 7 days of age with respiratory rate equal to or greater than 60 breaths per minute and no other signs of illness	Refer to district hospital		If referral not feasible: Treat with dispersible oral amoxicillin (50 mg/kg per dose) twice per day for 7 days
○ Clinical severe infection (CSI): young infant with one or more of the following signs: not feeding well, high body temperature (≥ 38°C), low body temperature (< 35.5°C), severe chest in-drawing, movement only when stimulated.	Refer to district hospital		If referral not feasible: Treat with once daily gentamicin injection (5–7.5 mg/kg) for 2 days and dispersible oral amoxicillin (50 mg/kg per dose) twice per day for 7 days
○ Critical illness: young infants with any of the following signs: convulsions, unable to feed at all, no movement on stimulation, unable to cry, bulging fontanelle and cyanosis (SpO2<90%).	Refer to district hospital		If referral not feasible: Reinforce referral and provide rescue antibiotic treatment (twice daily ampicillin and once daily gentamicin injection (5–7.5 mg/kg))
Fast breathing only: young infants 7–59 days of age with respiratory rate equal to or greater than 60 breaths per minute and no other signs of illness	Treat on outpatient basis		Treat with dispersible oral amoxicillin (50 mg/kg per dose) twice per day for 7 days
Outcome definitions
Primary		Secondary
• Treatment completion: ○ CSI: proportion of young infants with signs of CSI who completed outpatient treatment as per protocol—both doses of gentamicin and at least 12 of 14 amoxicillin doses; ○ Fast breathing only: proportion of young infants with only fast breathing who completed treatment as per protocol—at least 12 out of 14 amoxicillin doses).		• Refusal of referral advice and acceptance of outpatient treatment: proportion of young infants with signs of CSI or only fast breathing 0–6 days of age identified at first-level facilities that accepted outpatient treatment • Mandatory day 4 follow up: proportion of young infants with signs of CSI or only fast breathing treated on an outpatient basis who complete mandatory Day 4 follow-up visit at a health facility • HSA follow up: proportion of young infants with signs of CSI or only fast breathing treated on an outpatient basis who receive a day 3 follow-up home visit from an HSA • Treatment failure: proportion of young infants with signs of CSI or only fast breathing treated on an outpatient basis who experienced clinical deterioration defined as: emergence of any sign of critical illness or a new sign of CSI, persistence of same sign(s) on day 4, not recovered by day 8, re-emergence of any presenting sign after disappearance on day 4 and any severe adverse events* • Outcome of illness: proportion of young infants with signs of critical illness, CSI or only fast breathing who at day 14 were: i) better; ii) still sick; iii) outcome unknown; or iv) dead

*Severe adverse events: Death; Diarrhoea with severe dehydration; Disseminated and severe rash; Anaphylactic reaction (Within 30 minutes of getting the antibiotic dose, sudden development of breathing difficulty and raised wheals); Stopped passing urine for >12 hours (Renal failure); Cellulitis or abscess at injection site (only in those receiving injections)