Journal Article

Seven-day versus 14-day antibiotic course for culture-proven neonatal sepsis: a multicentre randomised non-inferiority trial in a low and middle-income country

Sharma, Madhu, Kumar, Praveen, Tripathi, Shalini, Ray, Pallab, Makkar, Nisha, Shivanna, Niranjan, Jagannatha, Bhavana, Nagaraj, Savitha, Shukla, Amlin, Gathwala, Geeta, Bandiya, Prathik, Sundaram, MangalaBharathi, Nesargi, Saudamini, Karthik, Arun, Venkatesh, Vimla, Randhawa, Valinderjeet Singh, Nangia, Sushma, Jain, Suksham, Saini, Anumeet, Mukundan, Lakshmi, Saigal, Karnika, Radhakrishnan, Devasena, Dalal, Poonam, Dhir, Maitreyi, Rasaily, Reeta, Benakappa, Naveen, Srivastava, Tanaya, Jajoo, Mamta, Mittal, Suruchi, Saili, Arvind, Chandramohan, Asmita, Pragati, R A, Malik, Meenakshi, Dogra, Sarita, Dutta, Sourabh, Kumar, Mala

2025

Overview

ObjectiveDefinitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis.DesignRandomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.PatientsNeonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted. Exclusions: Staphylococcus aureus or fungal sepsis, and infections requiring prolonged antibiotics. We planned to enrol 350 per group, assuming 10% rate of primary outcome, +7% non-inferiority margin, one-sided 5% alpha, 90% power, 10% loss to follow-up.Intervention7 days (no further treatment); comparison: 14 days (7 days postrandomisation).OutcomesPrimary: relapse (definite or probable) within day 21 postantibiotic completion. Secondary outcomes: composite of mortality or definite/probable/secondary sepsis and duration of hospitalisation. One interim analysis (per protocol (PP)) was planned.Results126 and 135 subjects were recruited in 7-day and 14-day groups, respectively, with mean (SD) birth weight (BW) 2250.9 (741.1) and 2187.8 (718.8) g. The trial was terminated early, based on interim PP analysis. 2/125 and 6/130 subjects had the primary outcome in 7-day and 14-day groups, respectively (risk difference (RD)=−3.0% (99.5% CI −9.2%, +3.1%), below non-inferiority margin). The composite secondary outcome also favoured the 7-day regimen (RD: −3.7% (99.5% CI −12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: −4 days (95% CI −5 to –3)).ConclusionsA 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.Trial registration number NCT03280147.

• Publisher: BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health,BMJ Publishing Group LTD
• Subject: Anti-Bacterial Agents - administration & dosage / Antibiotics / Birth weight / Clinical medicine / Developing Countries / Drug Administration Schedule / Drug resistance / Evidence / Failure / Female / Humans / Infant, Newborn / Length of Stay - statistics & numerical data / Male / Meningitis / Meta-analysis / Multidrug resistant organisms / Neonatal Sepsis - drug therapy / Neonatal Sepsis - microbiology / Neonatal Sepsis - mortality / Neonates / Neonatology / Original research / Pathogens / Sepsis / Therapeutics / Time Factors / Treatment Outcome