645 - Absence of Toxemia in Clostridioides difficile infection: Results from Ultrasensitive Toxin Assay of Serum

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Presenting Author(s)

Rebecca Sprague

Clinical Research Assistant
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

KW

Karolyne Warny

Student Intern
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Nira R. Pollock

Associate Medical Director, Infectious Diseases Diagnostic Lab/Associate Professor of Pathology and Medicine, HMS
Boston Children's Hospital
Boston, MA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
KD

Kaitlyn Daugherty

Clinical Research Assistant II
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
QL

Qianyun Lin

Dr.
Beth Israel Deaconess Medical
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
HX

Hua Xu

Researcher
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CC

Christine Cuddemi

Clinical Research Coordinator
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CB

Caitlin Barrett

Clinical Research Assistant I
BIDMC
Brookline, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
AB

Alice Banz

Staff scientist
biomerieux
Marcy L’Etoile, Auvergne, France
Disclosure: BioMerieux (Employee)
AL

Aude Lantz

Staff Scientist
bioMérieux
Lyon, Rhone-Alpes, France
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Kevin W. Garey

Professor and Chair
University of Houston
Houston, TX
Disclosure: Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)
Anne J. Gonzales-Luna

Assistant Professor
Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy
Houston, TX
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CA

Carolyn D. Alonso

Principal Investigator
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: Alnylam Pharmaceuticals (Employee)Merck (Research Grant or Support)
JV

Javier A. Villafuerte Galvez

Gastroenterology Fellow
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CK

Ciarán Kelly

Professor of Medicine
Beth Israel Deaconess Medical Center
Boston, Massachusetts
Disclosure: Artugen (Consultant)Facile Therapeutics (Consultant)Finch (Consultant)First Light Biosciences (Consultant)Matrivax (Consultant)Merck (Consultant)Vedanta (Consultant)

Background: Clostridioides difficile infection (CDI) is the major cause of hospital-acquired bacterial infectious diarrheacaused by Toxin A (TcdA) and Toxin B (Tcd B), secreted from pathogenic strains of C.difficle bacteria. This infection can vary greatly in symptom severity and presentation. In fulminant CDI, these toxins lead to systemic complications such as toxemia, however, identification of toxemia in CDI patients is extremely rare. We hypothesized that this rarity of detection may be due to low concentrations of circulating toxins in the blood, below the limit of detection of commercially available assays.

Methods: The previously developed Single Molecule Array (Simoa) assay, capable of detecting TcdA and TcdB in stool, was modified for the detection of toxins in serum and applied to a panel of serum samples from patients with confirmed CDI.

Results: Our cohort included 169 patients with a median age of 68 years (IQR 54-78), most with severe CDI and many with severe clinical outcomes attributed to CDI (Table 1). We found no detectable TcdA or TcdB in the serum of our patient cohort despite a wide range of toxin concentrations in paired stool (Figure 1). The detection of toxin may be limited by the interference of anti-toxin anti-bodies circulating in serum. When serum samples were spiked with TcdA and/or TcdBvarying amounts of IgA, IgG or IgM anti-toxin, high serum anti-toxin antibody concentrations were associated with loss of Simoa signal, suggesting substantial inhibition of toxin measurements. Table 1. Demographics, Baseline Laboratory Values, and Clinical Outcomes for the cohort

Figure 1. Comparison of TcdA and TcdB concentrations, as measured by Simoa, in serum and stool. Clinical cutoffs are shown: stool, 20 pg/ml for TcdA and for TcdB; serum 15.0 pg/ml for TcdA and is 26.7 pg/ml for TcdB. Signals below these cut-offs are below backgrounds and so negative.

Conclusion: In contrast to earlier published findings which reported on the presence of detectable toxin in the serum of a small number of patients with CDI, our work did not support this observation. Although Simoa is highly sensitive for detection of picogram quantities of TcdA or TcdB it was unable to detect either toxin in serum during CDI. This result does not support the hypothesis that toxemia develops even in severe C. difficile infection.