Fecal lactoferrin as a biomarker for determining disease severity and for treating infection in patients with clostridium difficile disease

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.

1 . A method of treating a patient with  C. Difficile  disease, the method comprising:
 administering a therapeutically effective amount of treatment shown to be effective in treating moderate-to-severe  C. Difficile  to a patient who has tested positive for an elevated level of one or more of lactoferrin or calprotectin in a fecal sample indicating severe intestinal inflammation.   
     
     
         2 . The method of  claim 1 , wherein the level of one or more of lactoferrin or calprotectin in the fecal sample is determined through use of a quantitative enzyme immunoassay (EIA). 
     
     
         3 . The method of  claim 1 , wherein the elevated level of lactoferrin is 100 μg/mL or greater in the fecal sample. 
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective treatment is one or more of glycopeptide antibiotics or macrocyclic antibiotics. 
     
     
         5 . The method of  claim 1 , wherein the therapeutic treatment is a native flora transplant. 
     
     
         6 . A method of treating a patient with  C. Difficile  disease, the method comprising:
 administering a therapeutically effective amount of treatment shown to be effective in treating moderate  C. Difficile  to a patient who has tested positive for an elevated level of one or more of lactoferrin or calprotectin in a fecal sample indicating moderate intestinal inflammation.   
     
     
         7 . The method of  claim 6 , wherein the level of one or more of lactoferrin or calprotectin in the fecal sample is determined through use of a quantitative enzyme immunoassay (EIA). 
     
     
         8 . The method of  claim 6 , wherein the elevated level of lactoferrin is 7.25 μg/mL to 99.99 μg/mL in the fecal sample. 
     
     
         9 . The method of  claim 6 , wherein the therapeutically effective treatment is one or more nitroimidazole antibiotics. 
     
     
         10 . The method of  claim 6 , wherein the therapeutically effective treatment is a native flora transplant. 
     
     
         11 . A method of diagnosing a patient with a severity of  Clostridium Difficile  disease, the method comprising:
 obtaining a fecal sample from a person having been diagnosed with  C. difficile  disease;   determining whether an elevated level of one or more of lactoferrin or calprotectin is present in the fecal sample; and   upon determining that an elevated level of one or more of lactoferrin or calprotectin is present in the fecal sample, identifying a severity of the  C. difficile  disease based on a level of one or more of lactoferrin or calprotectin present in the fecal sample.   
     
     
         12 . The method of  claim 11 , wherein the level of one or more of lactoferrin or calprotectin in the fecal sample is determined through use of a quantitative enzyme immunoassay (EIA). 
     
     
         13 . The method of  claim 11 , wherein the elevated levels of lactoferrin is 100 μg/mL or greater in the fecal sample and the severity of  C. Difficile  disease is considered moderate-to-severe. 
     
     
         14 . The method of  claim 13 , wherein the therapeutically effective treatment is one or more of glycopeptide antibiotics or macrocyclic antibiotics. 
     
     
         15 . The method of  claim 13 , wherein the therapeutically effective treatment is a native flora transplant. 
     
     
         16 . The method of  claim 11 , wherein the elevated levels of lactoferrin is 7.25 μg/mL to 99.99 μg/mL in the fecal sample and the severity of  C. Difficile  disease is considered moderate. 
     
     
         17 . The method of  claim 16 , wherein the therapeutically effective treatment is one or more nitroimidazole antibiotics. 
     
     
         18 . The method of  claim 11 , wherein the elevated levels of lactoferrin is less than 7.25 μg/mL in the fecal sample and the severity of  C. Difficile  disease is considered mild, wherein the therapeutically effective treatment is no treatment. 
     
     
         19 . The method of  claim 11 , wherein the level of one or more of lactoferrin or calprotectin used to determine disease severity in patients diagnosed with  C. difficile  is combined with one or more of the following:
 clinical symptoms comprising one or more of a number of unformed stools per day, a presence of fever, abdominal pain, and vomiting, and   lab parameters comprising one or more of C-reactive protein (CRP), white blood cell count (WBC), serum albumin, and creatinine.   
     
     
         20 . The method of  claim 11 , wherein the diagnosis of  C. difficile  was concluded based upon presence of a biomarker that indicates a presence of toxigenic  C. difficile.