Research Reveals Potential New Marker for Mortality Due to Clostridium difficile Infection

When it comes to addressing health care-associated infections, Clostridium difficile, remains, well, difficult.

Research suggests that illness due to C difficile is the most common nosocomial infection in the United States, with mortality rates as high as 22%. Yet, a new study published on September 12 in JAMA Surgery suggests there may be a—relatively—simple and cost-effective solution: by identifying patients at risk for poor outcomes caused by C difficile infection using serum eosinophil count information collected at hospital admission.

“There’s a frequently obtained, but often underutilized, marker that can predict not only mortality but adverse outcomes in disease,” study co-author David B. Stewart, MD, FACS, FASCRS, associate professor and section chief, colorectal surgery, University of Arizona, told Contagion®. “Eosinophil count is a marker we often ignore because, in general, it’s relatively unimportant for the bacterial infections we deal with. However, what our research shows that undetectable levels of eosinophils at the time of admission can be an accurate predictor of disease severity.”

For their research, Dr. Stewart and his colleagues performed a cohort study 2065 adult patients admitted for C difficile infection through the emergency departments of 2 tertiary referral centers over a 10-year period. The study population was then stratified based on eosinophil count (0.0 cells/μL or >0.0 cells/μL) at the time of admission, and divided into a training and validation cohort. The authors used multivariable logistic regression to construct a predictive model for inpatient mortality as well as other disease-related outcomes.

What they found is that of the 2065 patients in the study (52.9% of whom were women; participants had a mean age of 63.4 years), those with an undetectable eosinophil count at admission had increased in-hospital mortality in both the training and validation cohorts. In addition, undetectable eosinophil counts were associated with indicators of severe sepsis “such as admission to monitored care settings, the need for vasopressors, and emergency total colectomy,” according to the authors.

Other significant predictors of C difficile infection mortality at admission included other readily obtainable and easily available markers such as comorbidity burden and lower systolic blood pressures. A subgroup analysis of patients presenting with no initial tachycardia or hypotension revealed that only those with undetectable admission eosinophil counts, but not those with elevated white blood cell counts, “had significantly increased odds of inpatient mortality” due to C difficile infection. In fact, the multivariable logistic analysis revealed that undetectable eosinophil levels (eosinopenia) had greater than 90% accuracy among patients with a predicted probability of mortality of more than 20%.

According to Dr. Stewart, the JAMA Surgery paper is the first human study to follow up on the work of co-author William A. Petri, MD, PhD, Wade Hampton Frost Professor of Medicine and chief, division of infectious disease, University of Virginia, who had explored the relationship between eosinophil levels and C difficile infection mortality in mice. Given that most emergency departments call for complete blood counts and differentials for every new patient that’s admitted, obtaining eosinophil counts for patients shouldn’t be a costly or inefficient step to take; it would merely entail accessing data that has already been collected, in most cases.

“What we demonstrate in our present study is that eosinophil counts at the time admission are strongly predictive of outcomes with relation to C difficile infection,” Dr. Stewart explained. “Now, we need to look determine, if we were to change the management of patients based on that information, would that change outcomes? [As such,] we are in the planning stages of a prospective clinical trial to see if we can lower the incidence of adverse events like the need for vasopressors and emergency total colectomy by responding to that information.”

In a related commentary published with the study, authors from the department of surgery at McGovern Medical School at the University of Texas Health Science Center in Houston wrote that “admission eosinopenia may be a novel and inexpensive prognosticator for guiding the management of [C difficile infections]. Moreover, there are data to suggest that the resolution of eosinopenia may be a marker for a response to antimicrobial therapy in infections. Ultimately, interventions to block the TLR2-dependent pathway or to restore eosinophil cell counts may have therapeutic potential in [C difficile infections].”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous health care-related publications. He is the former editor of Infectious Disease Special Edition.