Investigators Test Predictors of C Difficile Infection Severity

Ching-Chi Lee, MD

New research has cleared up some beliefs regarding leukocyte counts and serum creatinine levels and the risk of mortality due to Clostridioides difficile infection (CDI).

A team, led by Ching-Chi Lee, MD, Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, examined the association between 2 key predictors and severe C difficile infections.

In the past, investigators identified a leukocyte count of at least 15,000 cells/mL and serum creatinine greater than 1.5 mg/dl as predictors of severe C difficile infections, including treatment failure, prolonged hospitalization, and mortality. However, it is known whether there is an association between the differential ratios of blood leukocytes and the prognosis of CDI.

“During CDI, neutrophils are the major defense cells that infiltrate affected intestinal tissue and participate in pathogen clearance,” the authors wrote. “Therefore, neutrophilic infiltration in the gut is an important process in CDI.”

The Study

In the study, the investigators examined 235 hospitalized patients with hospital-onset CDI at the medical wards of Tainan Hospital, Ministry of Health and Welfare in Taiwan between January 2013 and April 2020. The average age of the patient population was 75.7 years and 51.5% were female. In addition, 62% (n = 146) of the patients had non-severe C difficile infections and 38% (n = 87) had severe CDI.

Associations

Overall, the severe C difficile infection cohort had a higher crude in-hospital mortality rate than the patients with non-severe CDI (35.6% vs 18.5%; P = 0.005).

Using a multivariate analysis, the investigators did not identify an association between a leukocyte count of at least 15,000 cell/mL at the onset of infection and in-hospital mortality (OR, 1.66; P = 0.21).

On the other hand, there was an independent association between in-hospital mortality and a neutrophil ratio greater than 75% (OR, 2.65; P = 0.02), serum creatinine of at least 1.5 mg/L (OR, 3.42; P = 0.03), and CDI caused by isolates harboring the tcdC gene (OR, 3.54; P = 0.02).

The investigators also found patients with a neutrophil ratio greater than 85%, between 80-85%, or between 75-80% of serum leukocytes had a higher mortality rate (34.8%, 30.3%, or 34.4%, respectively) than patients with a neutrophil ratio of 70-75% or ≤75% (12.5% or 13.9%, respectively).

There were also other trends identified. For example, the 177 surviving patients were more likely to be male (52.5% vs 36.2%, P = 0.04) and less likely to have prior penicillin exposure within one month before CDI onset (9.6% vs 19.0%, P = 0.06), compared to the 58 patients who died throughout the study.

“Serum creatinine > 1.5 mg/L, a high neutrophil ratio of blood leukocytes (> 75%), and the causative C. difficile harboring the tcdC gene was independent prognostic predictors in hospitalized adults with CDI,” the authors wrote.

The study, “Neutrophil Ratio of White Blood Cells as a Prognostic Predictor of Clostridioides difficile Infection,” was published online in the Journal of Inflammation Research.