Management of Antibiotic-Associated Diarrhea After C. difficile Infection With a Serum-Derived Bovine Immunoglobulin Preparation

Abstract

Clostridium difficile infection (CDI) has a high mortality, morbidity and large economic cost and can cause mild diarrhea to a fulminant, life threatening colitis. Antibiotics, though effective can lead to antibiotic-associated diarrhea (AAD). Serum-derived bovine immunoglobulin (SBI) has been shown to bind/neutralize toxins A&B from hypervirulent ribotypes in vitro and reduce CDI-induced mortality by 50% in a low-protein fed mouse model. Due to these activities and its reported efficacy in managing chronic loose and frequent stools, SBI was administered to 4 patients with CDI experiencing AAD. Patient 1 (89 yrs Caucasian female) had a history of severe CDI in 2012 unresponsive to metronidazole requiring vancomycin for 2-wks and a 1-mo taper. Following a urinary tract infection resolved with antibiotics, CDI reoccurred and was resolved with additional vancomycin, but the patient had AAD unresponsive to loperamide. Patient 2 (76 yrs Caucasian male) had CDI-induced colitis treated with a 20-day course of metronidazole, but had continued diarrhea. Probiotics had no effect. Patient 3 (59 yrs Caucasian female) had a history of chronic IBS-C, controlled by lubiprostone. After an upper respiratory tract infection treated with amoxicillin/clavulanic acid, she developed severe, watery, foul smelling stools (8-12/d) within 48 hrs. The patient was switched to azithromycin and discontinued lubiprostone. Despite switching to azithromycin, it did not stop her diarrhea and was found to be CDI positive by PCR. Patient 4 (89 yrs Caucasian male) had myelodysplatic syndrome, ASCVD s/p CABG, was hospitalized with acute exacerbations of COPD treated with IV piperacillin/tazobactam, and developed diarrhea on day 4. PCR stool analysis revealed CDI and the patient was switched to oral vancomycin. Post-discharge, his diarrhea persisted after 5 days of vancomycin therapy. Patient 1 was given SBI 5g BID and after 1-week had improved stool consistency/frequency and a better sense of well-being. Patient 2 received SBI 5g TID for 9-d and it managed chronic loose and frequent stools. Patient 3 dosed with SBI 5g BID had normal stool frequency/consistency within 72 hrs. He was maintained asymptomatically on SBI for 30-d. Despite a positive CDI stool test by PCR, routine colonoscopy 6-wks later revealed no clinical signs of disease. Watery stools in Patient 4 were managed with the combination of 200mg fidaxomicin BID and SBI 5g BID after 48 hrs. After the 10-day course of fidaxomicin, SBI was continued for an additional 14-d with no recurrent symptoms. It is hypothecized that SBI may help restore normal barrier function by binding to microbial components produced after antibiotic therapy, thereby reducing immune activation which degrades the intestinal barrier. These cases suggest that SBI is useful in helping nutritionally manage AAD.