Characteristics of neonates with culture-proven bloodstream infection who have low levels of C-reactive protein (≦10 mg/L)

Background: Elevated C-reactive protein (CRP) level is widely used in clinical practice as a marker to distinguish between neonates with or without sepsis. However, some neonates with bacteremia have a CRP level within the normal range and they are not well characterized. Methods: All episodes of neonatal culture-proven bloodstream infections (BSIs) between July 2004 and June 2012 were enrolled. Patients characteristics were compared for three CRP groups (low, ≤ 10 mg/L; intermediate, 11-100 mg/L; and high, > 100 mg/L) using the Chi-square test and one-way ANOVA. The sepsis-attributable mortality rates were compared using logistic regression analyses. Results: Of 986 episodes of neonatal BSI, 247 (25.1 %) had CRP ≤10 mg/L at the onset of clinical sepsis. In the low CRP group, patients had lower gestational age and birth weight, and an earlier occurrence of BSI. Patients with underlying gastrointestinal pathology, renal disorders, cholestasis, and pulmonary hypertension had a non-significant elevated CRP level at the onset of sepsis. In the blood culture of the low CRP group, coagulase-negative staphylococci (CoNS) were relatively more common (55.9 %, p < 0.001) than the other two groups, although one-fourth were infected with gram-negative bacilli (19.0 %), fungi (2.8 %), or polymicrobial pathogens (3.6 %). Of the BSIs with initial low CRP, 29.1 % were treated with inadequate antibiotics, 13.0 % progressed to septic shock, and 5.3 % had infectious complications. The sepsis-attributable mortality rate was lower in the low CRP group (4.9 %) than in the high CRP group (13.6 %). Conclusions: A considerable proportion of neonatal BSIs had a normal or low initial CRP level (≤10 mg/L), which was more likely to occur in low birth weight or extremely preterm infants, those with earlier onset of sepsis, and those infected with CoNS. Plasma CRP level should not be used to rule out severe culture-proven sepsis or guide the empirical choice of antibiotics.