Heterogeneity of Critical Organ Dysfunction During Late-Onset Bacteremia in Preterm Infants

Importance: Late-onset sepsis in preterm infants is predominantly defined by bacteremia. Although binary classifications are critical for pathogen epidemiology and antibiotic stewardship efforts, they limit more granular understanding of the severity or organ dysfunction trajectory as experienced by individual infants. Objective: To quantify the heterogeneity of illness severity and organ dysfunction during late-onset sepsis episodes in preterm infants. Design, Setting, and Participants: Multicenter cohort study of first episodes of late-onset single-pathogen bacteremia in infants at 33 weeks' gestation or less at 4 academic neonatal intensive care units (January 2012 to February 2025). Main Outcomes and Measures: Neonatal Sequential Organ Failure Assessment (nSOFA) scores were calculated hourly from 48 hours before the index blood culture through 14 days after episode onset or death. Organ dysfunction trajectories, magnitude of change, severity, cumulative illness burden, and tempo (onset timing and topography) of burden accumulation across episodes were characterized, including those attributed to the same pathogen. Results: This study identified first episodes of late-onset bacteremia in 221 preterm infants (median gestational age, 27 weeks [IQR, 25-29 weeks]; birth weight, 840 g [IQR, 650-1210 g]; 116 [52%] male). Organ dysfunction at evaluation was frequently minimal among survivors (median nSOFA, 1; IQR, 0-3), yet subsequent trajectories varied markedly across episodes. Organ dysfunction change over time (median change in nSOFA of 3 [IQR, 0-6] and 0 [IQR, 2-7] by Gram stain, negative vs positive), peak severity (median maximum nSOFA of 6 [IQR, 1-9] and 3 [IQR, 0-9] by Gram stain), cumulative burden (median cumulative nSOFA of 311 [IQR, 0-666] and 238 [IQR, 0-531] by Gram stain), and temporal dispersion (70% minimum coefficient of variation) showed wide variability across episodes, even among those of the same pathogen. By 168 hours, cumulative burden remained highly dispersed, with some survivors accumulating minimal burden and others reaching substantial burden (median cumulative nSOFA, 250 hours [IQR, 0-600 hours]) as early as 24 hours. Conclusions and Relevance: In this cohort study of late-onset single-pathogen bacteremia in infants at 33 weeks' gestation or less, late-onset bacteremia in preterm infants was associated with substantial heterogeneity in the severity and temporal course of critical organ dysfunction. Characterization of organ dysfunction dynamics may provide a more informative framework for studying neonatal sepsis than binary microbiologic classifications alone.