Ribotype 027 Clostridium difficile infections with measurable stool toxin have increased lactoferrin and are associated with a higher mortality

Abstract

We evaluated clinical and diagnostic indicators of severe C. difficile infection (CDI) and their association with poor clinical outcome. A total of 210 patients positive according to PCR (toxin B: tcdB) were included, with patients having a median age of 62 years and a Charlson co-morbidity index (CI) score of 5. Ninety-one percent (n = 191) were positive by toxigenic culture and 61 % (n = 129) had stool toxin. Toxin-positive patients had significantly higher fecal lactoferrin (mean 316 μg/g versus 106 μg/g stool; p < 0.0001). Forty percent of patients (n = 85) were infected with ribotype 027 and significantly more of these patients had measurable stool toxin (79 % vs. 50 %; p < 0.0001). The mean fecal lactoferrin was significantly higher for toxin-positive 027 CDI compared with the 027 toxin-negative group (317 vs 60 μg/g; p = 0.0014). Ribotype 027 CDI with stool toxin showed a higher all-cause, 100-day mortality compared with non-027 with stool toxin (36 % vs 18 %; p = 0.017). Logistic regression univariate analysis for odds ratio (OR) and p values revealed that age (OR = 1.1), intensive care unit treatment (OR = 2.7), CI (OR = 1.2), 027 CDI (OR = 2.1), white blood cell count (OR = 1.0), albumin level (OR = 0.1), and stool toxin-positive 027 CDI (OR = 2.5) were significantly associated with 100-day mortality (p < 0.05). In conclusion, CDI PCR-positive patients with 027 infection and stool toxin have increased lactoferrin and are at an increased risk of death.

A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre

“…While Humphries et al (2013), reported no correlation between the presence of stool toxin as detected by EIA testing and disease severity, studies by Baker et al (2013) and Polage et al (2015) found that patient mortality and duration of symptoms were significantly reduced for patients with EIA-negative/ PCR-positive samples. Stool toxin titre is also an important factor in diagnostic test performance, and there is a relationship between faecal toxin load measured by cell cytotoxicity neutralization assay and clinical outcome (Boone et al, 2014;Planche et al, 2013).…”

Quantitative Fecal Lactoferrin as a Biomarker for Severe Clostridium difficile Infection in Hospitalized Patients

“…Elevated level of fecal lactoferrin was defined as ≥ 7.25 µg/mL [16,19]. A frozen fecal specimen from enrolled subjects on day of CDI diagnosis was shipped to TechLab, Inc., Blacksburg, VA for C. difficile isolation and PCR ribotyping [20]. …”

“…Additionally, fecal biomarkers of inflammation, such as fecal lactoferrin, have been used inflammatory bowel disease to provide an objective assessment of the intestinal inflammatory burden and disease severity [13–16]. Similarly, fecal lactoferrin may be a useful biomarker in predicting severity of intestinal inflammation in CDI [17–20]. In this study, we evaluated the current clinical definition of severe CDI in a cohort of hospitalized patients for predicting 3 month mortality.…”

The Contribution of Strains and Hosts to Outcomes in Clostridium difficile Infection

“…Fecal lactoferrin and interleukin-8 are produced in response to C difficile toxins and have been investigated as predictors of CDI disease severity. 41,42 They can readily be measured in stool samples and one study showed that patients with clinically severe CDI have fecal lactoferrin levels 5-fold greater than in mild/moderation infection. 42 Further clinical studies are required to define CDI-specific biomarkers for prospective clinical use.…”