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The Utility of Proadrenomedullin and Procalcitonin in Comparison to C-Reactive Protein as Predictors of Sepsis and Bloodstream Infections in Critically Ill Patients With Cancer*

Debiane, Labib MD1; Hachem, Ray Y. MD1; Al Wohoush, Iba MD1; Shomali, William MD1; Bahu, Ramez R. MD1; Jiang, Ying MS1; Chaftari, Anne-Marie MD1; Jabbour, Joseph BS1; Al Shuaibi, Munirah MD1; Hanania, Alexander BS1; Pravinkumar, S. Egbert MD, FRCP2; Schuetz, Philipp MD3; Raad, Issam MD, FACP, FIDSA, FSHEA1

doi: 10.1097/CCM.0000000000000526
Clinical Investigations
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Objectives: Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein.

Design: Single-center prospective cohort study.

Setting: Tertiary care, academic, university hospital.

Patients: One hundred fourteen critically ill patients with cancer with fever.

Interventions: None.

Measurements and Main Results: Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59–0.82) and procalcitonin (0.71; 95% CI, 0.60–0.83) compared with C-reactive protein (0.53; 95% CI, 0.39–0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients’ mortality within 2 months after their fever onset. Regarding patients’ response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71–0.92) and procalcitonin (0.73; 95% CI, 0.60–0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45–0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001).

Conclusion: In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.

1Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX.

2Department of Critical Care, The University of Texas MD Anderson Cancer Center, Houston, TX.

3Medical University Department, Kantonsspital Aarau, Tellstrasse, Aarau, Switzerland.

* See also p. 2632.

Supported, in part, by institutional funds/PCT provided by Thermo-Fischer.

Dr. Schuetz received support from Thermo Scientific Biomarkers (formerly B.R.A.H.M.S. AG) and bioMerieux to attend meetings and fulfill speaking engagements. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: rhachem@mdanderson.org

© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins