Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile

Background: Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality. Objective: To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures. Design: The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset culture proven sepsis from 1991-1998. The second phase (S2) was a prospective study that enrolled infants greater than or equal to 72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis. Results: S1: Of the 48 episodes of culture proven, late-onset sepsis, 54 % of the blood cultures were positive by 24 hours and 90 % by 48 hours. The most common presenting signs were desaturations (50 %) and increased gastric residuals (33 %): I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile,as compared to those with no sepsis. Seven (88 %) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs. 13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different. Conclusions. In both S1 and S2,a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.