Does procalcitonin, C-reactive protein, or interleukin-6 test have a role in the diagnosis of severe infection in patients with febrile neutropenia? A systematic review and meta-analysis

Purpose: The study aims to determine the usefulness of procalcitonin (PCT) and other blood markers for identification of bacterial infection among patients with febrile neutropenia (FN). Methods: The Medline, EMBASE, and Cochrane databases were searched for articles from 1966 to December 2012. We performed a search to identify articles that examined the diagnostic accuracy of PCT in patients with FN. Statistical analyses (fixed- or random-effect models) were conducted to summarize and calculate the sensitivity, specificity, likelihood ratios, and 95 % confidence intervals (CIs). Results: Twenty-seven studies were included (1960 febrile episodes) for PCT analysis, 13 (1712 febrile episodes) for C-reactive protein (CRP) analysis, and five (314 febrile episodes) for interleukin (IL)-6 analysis. Increased PCT levels (odds ratio [OR] 11.5; 95 % CI 7.6 to 17.3), raised CRP levels (3.3; 2.7 to 4.2), and raised IL-6 levels (10.0; 5.5 to 18.0) were significantly associated with bacterial infection. Overall positive likelihood ratio was 5.49 (4.04–7.45) for PCT, 1.82 (1.42–2.33) for CRP, and 3.68 (2.41–5.60) for IL-6. Overall negative likelihood ratio was 0.40 (0.31–0.51) for PCT, 0.40 (0.26–0.61) for CRP, and 0.33 (0.23–0.46) for IL-6. Conclusions: Of the three potentially useful markers, PCT had the best positive likelihood ratio and can be used to confirm the diagnosis of bacterial infections in patients with FN. Due to unacceptably high negative likelihood ratio, medical decision for stopping antibiotics based on PCT alone in this high-risk population may not be possible.