Antibiotic stewardship in the context of management of early onset neonatal sepsis-an evolving paradigm shift

Table 2 Summary of studies evaluating early onset neonatal sepsis management strategies

Ref.	Design	Population (gestation)	Sample size (n)	Intervention/comparison	Key outcomes	Antibiotic reduction	Safety data	Level of evidence (OCEBM)	Main findings
Berardi et al[40], 2016	Cohort	Term infants	7628	SPE	Antibiotic use	50%	No increase in adverse outcomes	2b	SPE safely reduced unnecessary antibiotic use
Kuzniewicz et al[4], 2017	Cohort	≥ 34 weeks	608014	Development of SRC	EOS prediction, antibiotic use	48%	No increase in missed EOS reported	2b	SRC reduced empirical antibiotic use significantly
Dhudasia et al[8], 2018	Implementation study	≥ 35 weeks	2059	SRC implementation	Antibiotic exposure	42%	No increase in adverse outcomes	2b	Significant reduction in antibiotic use with maintained safety
Achten et al[36], 2019	Systematic review + meta-analysis	≥ 34 weeks	172385	SRC vs standard care	Antibiotic use, safety	44% (pooled)	No increase in mortality or severe morbidity	1a	Strong evidence supporting safety and reduced antibiotic use
Goel et al[10], 2020	Retrospective comparison	≥ 34 weeks	1187	NICE vs projected SRC	Antibiotic use	50% (projected)	Safety not directly assessed	2b	SRC projected to reduce antibiotic use vs NICE
Morris et al[12], 2020	Retrospective cohort	≥ 34 weeks	75 EOS cases	NICE vs SRC	Sensitivity		SRC less sensitive in identifying EOS cases	2b	Potential risk of delayed/missed treatment
Vatne et al[42], 2020	Population cohort	Term infants	20584	SPE	Antibiotic exposure	50%	No increase in infection-related morbidity/mortality	2b	Reduced antibiotic exposure safely
Pettinger et al[38], 2020	Systematic review + meta-analysis	≥ 34 weeks	NR	SRC sensitivity	Sensitivity		Lower sensitivity vs categorical approaches	1a	Highlights potential safety limitation
van Hasselt et al[35], 2021	Observational study	≥ 34 weeks	4000	SRC implementation	Antibiotic use	30%-40%	No safety concerns reported	2b	Reduction in antibiotic prescribing
Kimpton et al[11], 2021	Observational comparison	≥ 34 weeks	502	NICE vs SRC	Antibiotic use, sensitivity	40%	Lower sensitivity vs NICE noted	2b	Reduced antibiotic use but potential sensitivity trade-off
Goel et al[34], 2022	Multicentre implementation	≥ 34 weeks	66362	Adapted SRC	Antibiotic use, safety	40%	No increase in morbidity/mortality	2b	Safe reduction in antibiotic exposure
Cavigioli et al[41], 2022	Prospective implementation	≥ 34 weeks	4363	SRC + SPE	Antibiotic use	45%	No increase in adverse outcomes	2b	Combined approach reduced interventions safely
Bain et al[44], 2022	Observational study	≥ 34 weeks	1209	Clinical monitoring (SPE-like)	Antibiotic use	35%-50%	No increase in adverse outcomes	2b	Monitoring approach reduced antibiotic exposure safely
Yew et al[13], 2024	Implementation study	≥ 34 weeks	8856	SRC implementation	Antibiotic use	45%	No increase in adverse outcomes	2b	Reduced antibiotic exposure in real-world setting
Vatne et al[43], 2025	Population-based study	≥ 34 weeks	54671	SPE	Antibiotic use, safety	50%	No increase in mortality, NICU admission, or readmission	2b	Strong large-scale safety and effectiveness evidence
van der Weijden et al[37], 2025	Cluster RCT	≥ 34 weeks	18479	SRC vs standard care	Antibiotic use, safety	30%-35%	No increase in adverse outcomes	1b	RCT evidence supporting reduced antibiotic use with maintained safety

EOS: Early-onset sepsis; SRC: Sepsis Risk Calculator; SPE: Serial Physical Examination; NICE: National Institute for Health and Care Excellence; RCT: Randomised controlled trial; NICU: Neonatal intensive care unit; OCEBM: Oxford Centre for Evidence-Based Medicine; NR: Not reported.