Procalcitonin as Adjunct Biomarker for Severe Clostridium difficile-associated Diarrhea

Abstract

Purpose: Procalcitonin (PCT) has recently emerged as a useful adjunct in severe bacterial infections. Interferon (INF) -γ released in response to viral infections attenuates up-regulation of PCT, making it more specific for bacterial infections. The utility of PCT has been evaluated in various infections, such as pneumonia (community-acquired and ventilator-associated), severe sepsis and shock, urinary tract infection and febrile neutropenia. Few studies have investigated the use of PCT in acute intra-abdominal processes such as perforation, ischemia, acute appendicitis and pancreatitis. However, there has been no study to date evaluating the use of PCT in Clostridium difficile-associated diarrhea (CDAD). The incidence of CDAD (hospital- and community-acquired) continues to rise. Its severity is assessed by WBC count ≥15,000 or a serum creatinine level ≥1.5 times the baseline level. The aim of this study was to evaluate levels of PCT in patients with CDAD versus those with diarrhea of other etiologies, and assess the correlation between elevated PCT levels and severity of CDAD. Methods: This study was conducted at a tertiary care center over a period of 16 months (February 2011 - July 2012). Data were collected from all patients with diarrhea irrespective of the admitting diagnosis. Patients with bacteremia, UTI, pneumonia or neutropenia were excluded. All these patients had serum PCT drawn on admission along with stool studies for Clostridium difficile antigen; if the latter was positive, confirmation was obtained using Clostridium difficile toxin assay by polymerase chain reaction. A total of 157 patients with CDAD and 512 with non-CDAD were included. WBC count and serum creatinine levels were obtained in all these patients (age 20-98 years). Medians and Interquartile ranges (IQR) were compared using Mann-Whitney test. Cutoffs, sensitivity and specificity were obtained from receiver operator characteristic (ROC) curve. The associations were determined by a linear regression. Results: Patients with CDAD have much higher levels of PCT than patients with diarrhea of other etiologies. A PCT cutoff of 0.5ng/ml provided sensitivity of 90% and a specificity of 98%. Elevated WBC (≥15,000) and rise in creatinine ≥1.5 times baseline value were associated with higher PCT levels in patients with CDAD; for elevated WBC levels are r2=0.04, p=0.013 and for rise in creatinine r2=0.13, p<0.0001. The median for patients were 3.4 ng/L (IQR 1.5 to 12.8) while the median for controls were 0.27 ng/mL (IQR 0.14 to 0.41). Conclusion: Procalcitonin may be a valuable adjunct biomarker in distinguishing diarrhea from CDAD.