Immunocompromised C Difficile Patients Demonstrate Lower Anti-Toxin Antibody Levels

Carolyn D. Alonso, MD

Immunocompromised patients might be particularly difficult to treat for Clostridioides difficile infections (CDI).

A team, led by Carolyn D. Alonso, MD, Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, characterized humoral immune response to C difficile toxins for patients with CDI in immunocompromised hosts (ICH).

In the prospective study, the investigators examined hospitalized adult patients with C difficile infections with or without immunosuppression, identified as having hematologic malignancy, active solid tumor, solid organ or stem cell transplantation, inflammatory bowel disease, autoimmune disease, congenital or acquired immunodeficiency, asplenia, chronic receipt of high dose steroids, or receipt of immunosuppressing medications within 12 months.

There was 98 total patients included in the study, 47 of which were immunocompromised hosts.

Differences

The researchers compared serum and stool antibody concentrations of IgM, IgG, and IgA to C difficile toxins A and B at baseline, as well as treatment days 3, and 10-14.

The overall serum anti-toxin A and B antibody levels were similar at baseline, but immunocompromised hosts at day 3 demonstrated lower serum levels of anti-toxin A IgG, anti-toxin A IgA, and anti-toxin B IgA (all P <0.05).

At day 10-14, lower anti-toxin A IgG concentrations were found in the immunocompromised host cohort (ICH, 21 ELISA units; IQR, 16.4-44.6) compared to non-ICH subjects (49.0 ELISA units; IQR, 21.5-103; P = 0.045).

Stool Analysis

In the stool analysis, the researchers observed lower concentrations of anti-toxin B IgA antibodies at both baseline and day 3 for the immunocompromised host patients.

There was a notable difference in concentrations of anti-toxin B IgA at day 3 (ICH, 6.7 ELISA units; IQR, 1.9-13.9; non-ICH, 18.1 ELISA units; IQR, 4.9-31.7; P = 0.003).

“ICHs with CDI demonstrated lower levels of C. difficile anti-toxin antibodies in serum and stool during early CDI therapy compared to non-ICHs,” the authors wrote. “These data provide insight into the humoral response to CDI in ICHs.”

C Difficile Risk Factors

New research shows a handful of biomarkers and clinical characteristics can help clinicians identify high risk individuals for CDI.

A team, led by Cornelis H. van Werkhoven, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, assessed the potential clinical characteristics and biomarkers to predict C difficile infections in patients receiving newly initiated antibiotic treatment with penicillin along with a beta-lactamase inhibitor, 3rd/4th generation cephalosporins, carbapenems, fluoroquinolones, or clindamycin.

The overall 90-day cumulative incidences of a first CDI episode was 1.9% (95% CI, 1.1-3.0).

The researchers did identify a handful of factors that helped to predict an increased CDI risk, including carbapenem treatment (HR, 5.3; 95% CI, 1.7-16.6), toxigenic C. difficile rectal carriage (HR, 10.3; 95% CI, 3.2-33.1), high intestinal abundance of Enterococcus spp. relative to Ruminococcus spp. (HR, 5.4; 95% CI, 2.1-18.7), and low Shannon alpha diversity index as determined by 16 S rRNA gene profiling (HR, 9.7; 95% CI, 3.2-29.7).

However, normalized urinary 3-indoxyl sulfate levels did not predict an increased C difficile infection risk.

The study, “Humoral Immune Response to Clostridioides difficile Toxins A and B in Hospitalized Immunocompromised Patients with C. difficile infection,” was published online in Open Forum Infectious Diseases.