BACKGROUND: Neonatal sepsis epidemiology has been adequately reported in tertiary-care hospitals. However, such data are scarce from district hospitals in low-income and middle-income countries. This study aimed to evaluate the incidence of sepsis, pathogen profile, and antimicrobial resistance among neonates admitted to the special newborn care units in district hospitals in India. METHODS: We prospectively enrolled neonates admitted to newborn units in five district hospitals in India between October, 2019, and December, 2021. Blood cultures were obtained from neonates who met prespecified criteria and were processed at the laboratories of the tertiary-care hospitals linked to each district hospital. Identification of pathogens and antimicrobial susceptibility testing was performed using the automated system
all isolates were confirmed using matrix-assisted laser desorption-ionisation-time of flight. The primary outcome was the incidence of culture-positive sepsis. The final label of culture-positive sepsis was assigned based on culture reports and clinical course. Multidrug resistance was defined as resistance to antibiotics in at least three of the six antibiotic classes, including third generation cephalosporins, carbapenems, and aminoglycosides. FINDINGS: The study enrolled 6612 neonates (3972 inborn [born at the same hospital] and 2640 outborn [referred from other hospitals or homes]). Mean gestation was 37·1 weeks and mean birthweight was 2540 g. 3357 (50·8%) neonates met clinical sepsis criteria. The overall incidence of culture-positive sepsis was 213 (3·2%
95% CI 0·6-14·4)
ranging from 0·6% to 10·0% across the five sites. The incidence was higher in outborn neonates than inborn neonates: 132 [5·0%] versus 81 [2·0%]. The case-fatality rate of culture-positive sepsis was 36·6% (95% CI 12·1-71·0). Gram-negative bacilli accounted for 156 (70·0%) of 223 organisms isolated: Klebsiella pneumoniae (51 [22·9%]), Escherichia coli (33 [14·8%]), and Enterobacter spp (26 [11·7%]) were the most common Gram-negative organisms. 75%-88% of isolates of K pneumoniae, E coli, Enterobacter spp, and Acinetobacter baumannii were multidrug resistant. INTERPRETATION: The high incidence of culture-positive sepsis, case-fatality rates, and multidrug resistance among common pathogens underscores an urgent need to strengthen infection prevention and control practices, establish blood culture facilities, and implement antimicrobial stewardship programmes in district-level hospitals in India. FUNDING: Bill & Melinda Gates Foundation. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.