Extended Barrier Precautions vs Hand Hygiene Alone and Neonatal Sepsis in Intensive Care Patients: The BALTIC Cluster-Randomized Clinical Trial

Abstract

Importance The effects of contact precautions (ie, gowns and gloves) for individual patients colonized with gram-negative (GN) drug-resistant bacteria on sepsis risk in neonates requiring intensive care remain to be clarified. Objective To evaluate the noninferiority of standard hand hygiene disinfection vs standard hygiene disinfection plus extended barrier precautions for infants colonized with third-generation cephalosporins–resistant GN bacteria (3GCR-GNB). Design, Setting, and Participants This cluster-randomized clinical trial was conducted from 2020 to 2023 in 12 German tertiary care neonatal intensive units caring for neonates with high risk for infections with GNB for 24 months, with crossover after 12 months. Follow-up and data curation were completed December 31, 2024, and statistical analysis was finalized on July 31, 2025. Intervention The intervention was standard hand hygiene disinfection compared with current recommendations, ie, hygiene disinfection plus extended barrier precautions with gowns and gloves for routine care of infants colonized with 3GCR-GNB. Main Outcomes and Measures The primary outcome was the rate of health care–associated GNB bloodstream infections (BSI) at infant level in all neonates requiring intensive care in the cluster, assuming 5% as noninferiority margin delta; secondary outcomes included transmission rates of 3GCR-GNB and rates of any infection. Results The primary analysis was based on an overall sample size of 12 sites with crossover at 12 months, making 24 clusters with 9731 neonates. During the standard hand hygiene disinfection periods, 22 of 4699 infants (0.5%) developed GNB BSIs at infant level, compared with 25 of 5032 infants (0.5%) cared for during the extended barrier precaution periods (risk difference [RD], −0.03%; 95% CI, −0.43% to 0.38%; noninferiority P