Fecal lactoferrin as a biomarker for determining disease severity and for treating infection in patients with Clostridium difficile disease
Inventors
Boone, James Hunter • Lyerly, David M. • Wilkins, Tracy D. • Carman, Robert J.
Assignees
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Publication Number
US-10295536-B2
Publication Date
2019-05-21
Expiration Date
Abstract
Clostridium difficile disease involves a range of clinical presentations ranging from mild to self-limiting diarrhea to life-threatening pseudomembranous colitis and megacolon. Cases of C. difficile are treated differently depending on severity of disease. Mild and moderate cases may be treated with metronidazole while moderate-to-severe and relapsing cases are often treated with vancomycin or fidaxomicin. The presence of C. difficile disease is detected using a biomarker panel that includes C. difficile antigen (GDH), toxins A and B, and fecal lactoferrin. In patients suspected of C. difficile disease, if GDH is detected indicating the presence of C. difficile, and then toxins A and/or B are detected to indicate toxigenic C. difficile and support a diagnosis of C. difficile-associated disease, fecal lactoferrin concentrations are measured to determine severity of the disease by indicating the amount of intestinal inflammation.
Core Innovation
The document describes using fecal lactoferrin as a non-invasive biomarker in C. difficile-associated disease. It measures lactoferrin in a fecal sample and stratifies disease severity, including identifying moderate-to-severe disease based on a measured lactoferrin level. The approach is presented as enabling patient stratification without invasive sampling.
The document further describes a strategy in which a biomarker panel may be used to confirm toxigenic C. difficile. It discusses biomarkers including GDH and toxins A/B to confirm toxigenic C. difficile, followed by measuring fecal lactoferrin to gauge intestinal inflammation severity. The document includes example lactoferrin thresholds for mild, moderate, and moderate-to-severe disease, including an example threshold of ≥100 μg/mL for moderate-to-severe disease.
The document also describes serial monitoring using fecal lactoferrin, and relates changes in lactoferrin to treatment response and to relapse or reinfection. It reports markedly higher mean lactoferrin in moderate-to-severe versus moderate versus mild disease states and correlations between GDH/toxin/lactoferrin and clinical disease states. Native flora transplant (fecal microbiota transplantation, FMT) is discussed as a treatment option for severe cases.
Claims Coverage
The partial content provides two independent claims (clm-00001 and clm-00005). Both independent claims share a common inventive structure: quantitatively determining moderate-to-severe disease using fecal lactoferrin at a threshold of at least 100 μg/mL, followed by administering a therapeutically effective treatment that comprises a native flora transplant.
Fecal lactoferrin-based severity determination for native flora transplant
Quantitatively measuring a level of lactoferrin in a fecal sample from a patient with a C. difficile infection; determining that the patient has moderate-to-severe C. difficile disease based on the measured lactoferrin level being equal to or greater than 100 μg/mL; and, subsequent to the determining, administering a therapeutically effective treatment comprising a native flora transplant.
Fecal lactoferrin-based severity determination for native flora transplant after diagnosis
Obtaining a fecal sample from a patient having been diagnosed with C. difficile disease; measuring the fecal sample for a level of lactoferrin; determining that the patient has moderate-to-severe disease based on the measured fecal sample having a level of lactoferrin equal to or greater than 100 μg/mL; and subsequent to the determining, administering a therapeutically effective treatment comprising a native flora transplant.
Across the independent claims, the core claim coverage centers on using fecal lactoferrin measured from a fecal sample to determine moderate-to-severe C. difficile disease at a threshold of ≥100 μg/mL, and then administering a therapeutically effective native flora transplant as treatment.
Stated Advantages
Enables stratification of C. difficile disease severity using a non-invasive biomarker (fecal lactoferrin).
Supports monitoring response over time via serial fecal lactoferrin measurements, with lactoferrin dropping with treatment and rising with relapse or reinfection.
Documented Applications
Treating a patient with a C. difficile infection/disease by using fecal lactoferrin to determine moderate-to-severe disease and then administering a therapeutically effective treatment comprising a native flora transplant (FMT).
Monitoring patient response in C. difficile-associated disease using serial fecal lactoferrin measurements, including tracking changes with treatment and relapse or reinfection.
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