Broadening Diagnostic Horizons: Specificity of Serial Negative CRPs in Predicting Blood Culture Negativity in Suspected Neonatal Sepsis

Background Neonatal sepsis is a root cause, among others, of mortality and morbidity among neonates in low-middle-income countries (LMICs). Blood culture remains the gold standard diagnostic tool in diagnosing sepsis; however, it may take 48 to 72 hours to be reported negative. Hence, there is a demand for a quicker alternative to blood cultures. C-reactive protein (CRP) is a potential candidate useful in ruling out sepsis and can be a potential substitute for blood cultures. This prospective study aims to identify whether serial negative CRPs in a suspected case of sepsis can predict negative blood culture and aid in the safe, early discontinuation of antibiotics. Methods The study included babies for whom antibiotics were started on suspicion of sepsis. Two CRP tests, 24 hours apart, were negative. Blood cultures were evaluated for growth at 48 hours and 5 days. The cost incurred with additional antibiotics after two negative CRPs was estimated. Results Among 100 babies enrolled (n=100), 90 (n=90) were suspected of early-onset and 10 (n=10) were suspected of late-onset sepsis. The median gestational age was 34 weeks (interquartile range (IQR): 31.75-35). The median first and second CRP values are 0.2 (IQR: 0.1-0.31) and 1.2 mg/dl (IQR: 0.4-2.02), respectively. All blood cultures (n = 100) were negative, with a 95% confidence interval of 0.96 to 1. Conclusion Two negative CRPs 24 hours apart are sufficient to rule out sepsis with high confidence and predict a negative blood culture for microbial growth. Thus, antibiotics can be stopped following two negative CRPs.