Elevation of CRP precedes clinical suspicion of bloodstream infections in patients undergoing hematopoietic cell transplantation

Objectives: We aimed to examine whether C-reactive protein (CRP) elevation precedes the clinical signs and symptoms of infection among patients undergoing allogeneic hematopoietic cell transplantation (HCT). Methods: Prospective cohort of patients undergoing allogeneic HCT in whom daily blood samples for CRP were taken. In a nested case-control study, cases were defined as patients with clinically-significant bloodstream infection (BSI). Controls were defined as afebrile patients without infection, matched by age, time after transplantation and GVHD status. We calculated the mean difference (MD) between CRP 1 day before clinical suspicion of infection (day -1) and days -2 and -3 (deltaM1M2 and delta M1M3, respectively) and compared cases vs. controls. Results: From January 2010 to April 2012 we identified 46 cases of BSIs. The difference between the mean delta M1M3 and delta M1M2 in cases and controls were significantly higher in patients with BSI compared to controls (MD=5.9, 95% CI 3.5-8.3, p<.001 and MD=4.2mg/dl, 95% CI 2.2-6.2, p<.001, respectively). In the overall cohort, sensitivity, specificity, positive and negative predictive values of a daily delta value >4mg/dl were 52%, 98%, 66% and 98%, respectively. Conclusions: A daily increase of CRP blood levels of >4mg/dl in afebrile HCT recipients should trigger an evaluation for infection.