Effectiveness, cost effectiveness and experiences of switching from intravenous to oral antibiotics in neonates with probable early onset sepsis: a systematic review

ObjectiveTo assess the effectiveness, cost-effectiveness and experiences of switching from intravenous antibiotics to oral antibiotics in neonates with suspected early onset sepsis (EOS). DesignSystematic review. PatientsClinically stable term and later preterm neonates with suspected EOS. InterventionsOral antibiotics. Main outcome measuresMortality and morbidity, cost and resource use, family related and process outcomes and experiences of families and health care professionals. Information sourcesWe searched Medline, Embase, PsycINFO, HMIC, SPP, CENTRAL, CINAHL and Conference Abstracts (via Web of Science) in April 2025. Database searches were supplemented with citation chasing, contacting authors and website searches. MethodsScreening, data extraction and critical appraisal was performed in duplicate. Due to heterogeneity of outcomes, timepoints and lack of reported data relating to the data distribution, a narrative synthesis was performed. The review was informed by public collaborators interested in maternal health. ResultsAfter de-duplication, 3803 titles and abstracts were screened for relevance with 27 assessed for eligibility at full text. Following title and abstract screening, one randomised controlled trial (504 neonates) and three observational studies (795 neonates) were included. Length of stay was reduced by between 1 to 4 days across all four studies. No differences were observed between study arms in those reporting on readmission rates, reinfection or mortality. ConclusionsThis systematic review suggests that switching clinically stable term and late pre-term neonates with suspected EOS from intravenous to oral antibiotics can reduce hospital stay and healthcare costs without increasing morbidity, mortality, or readmission. Key messagesO_LIWhat is already known on this topic C_LI Intravenous antibiotics are commonly prescribed in neonatal care to treat suspected early onset sepsis (EOS). Distinguishing infectious from non-infectious cases is difficult, often leading to unnecessary intravenous antibiotic treatment in uninfected neonates. A recent systematic review of oral antibiotics for neonatal infections concluded that in general, adequate serum levels can be achieved after oral administration of antibiotics in neonates. O_LIWhat this study adds C_LI There is promising evidence that switching clinically well, term and late preterm neonates with suspected EOS from intravenous to oral antibiotics reduces duration of hospital stay with no impact on readmissions, clinical deterioration, mortality, or reinfection. O_LIHow this study might afect research, practice or policy C_LI Future research should focus on longer-term outcomes such as effects on the gut microbiome and later childhood health, evaluations of cost-effectiveness, incorporating both healthcare system and family perspectives, and ensure that equity considerations are fully addressed.