Antimicrobial resistance and treatment mismatch in culture-proven sepsis among very preterm infants in Chinese NICUs: a cohort study

Background: The real-world effectiveness of guideline-recommended antibiotics for neonatal sepsis remains uncertain in settings with high antimicrobial resistance. Evidence derived from large-scale, contemporary data that integrates pathogens, resistance, and treatment is needed. This study aims to assess the epidemiology, antimicrobial resistance, and antibiotic treatment practices for sepsis among very preterm infants (VPIs) in China. Methods: We analysed prospectively collected data from all VPIs admitted to 88 tertiary neonatal intensive care units (NICUs) in the Chinese Neonatal Network between 2019 and 2022. Findings: Among 38,560 VPIs, 1.1% (95% CI 1.0-1.2) developed early-onset sepsis (EOS; case-fatality 24.0%, 95% CI 19.8-28.8), and 5.8% (95% CI 5.6-6.1) developed late-onset sepsis (LOS; case-fatality 12.2%, 95% CI 10.9-13.7). Gram-negative bacteria predominated in both EOS (59.0%) and LOS (48.3%), with resistance to cefotaxime and ceftazidime reaching 69.8% and 28.6% in EOS, and even higher rates in LOS. An ampicillin plus ceftazidime regimen would fail to cover 13.3% of EOS cases, while gentamicin-based regimens showed comparable coverage. Nearly all Gram-positive EOS pathogens were susceptible to penicillin/ampicillin, yet 16.6% of definitive therapy involved vancomycin or linezolid. Broad-spectrum antibiotics were frequently continued after pathogen identification in both EOS and LOS, with insufficient de-escalation. Interpretation: Sepsis remains a major burden among VPIs in China, with Gram-negative bacteria exhibiting alarming resistance and mismatches between guideline-recommended regimens and real-world effectiveness. These findings highlight the need to integrate susceptibility and prescribing data to inform national guideline updates and targeted antimicrobial stewardship strategies. Funding: This work was funded by China Medical Board (grant #20-370).