clostridium difficile has become an increasingly important and common cause of healthcare - associated infections , accounting for almost half a million infections in the united states in 2011 with over 29,000 deaths within 30  days of the initial diagnosis . clostridium difficile infections ( cdi ) typically manifest as antibiotic - associated diarrhea and range in severity from asymptomatic silent carriers to severe life - threatening toxic megacolon . over the past decade , the incidence of these infections continues to increase with a trend towards more severe disease . the standard of care in management is antimicrobials with increasing use of fecal microbiota transplants . this case reports presents a patient with severe refractory nap-1 pseudomembranous cdi who failed these mainstay therapies and only had symptom alleviation following infusion of intravenous immunoglobulin ( ivig ) . the patient was a 68-year - old man with a history of coronary artery disease , chronic kidney disease on hemodialysis , hypertension , and severe peripheral arterial disease who initially presented to the hospital with worsening right lower extremity ischemia . two weeks prior to admission , he had been hospitalized at two outside hospitals with similar rest pain and was recommended to undergo a below - knee amputation ( bka ) . during the course of these hospitalizations , he was also diagnosed with clostridium difficile infection , treated effectively with oral metronidazole with complete resolution of abdominal pain and diarrhea . upon presentation , he was admitted to the vascular surgical service for chronic right leg ischemia with tissue gangrene . he developed sepsis and was started on intravenous vancomycin and piperacillin - tazobactam prior to surgery , which occurred four days after admission . he tolerated the procedure ; however , approximately one week post - operatively , he developed severe frequent episodes of watery diarrhea , found to be infected with the nap-1 strain of clostridium difficile identified by pcr assay . over the course of two months , he failed multiple therapeutic modalities for clostridium difficile infection including antimicrobials and two fecal microbiota transplants . guided by the infectious disease and gastroenterology specialists , he was treated with oral vancomycin , rectal enemas of vancomycin , and both intravenous and oral metronidazole . his condition deteriorated with worsening leukocytosis , transverse colonic distension on abdominal x - ray measuring approximately 67  cm , and persistent severe abdominal pain with 2025 watery bowel movements per day . he underwent a colonoscopy - guided fecal microbiota transplant ( bacteriotherapy ) with open biome 37 - 0020-d in the cecum , followed by a trial of cholestyramine . approximately one week after the first fecal transplant , his symptoms worsened . at that time , imaging with ct abdomen / pelvis with contrast showed severe , diffuse pancolitis with wall thickening , pericolonic inflammatory changes , surrounding ascites fluid , and increased distension of the colon . this significant worsening of infection burden despite fecal transplants and standard antimicrobials prompted a discussion between the specialists to opt for surgical resection versus a trial of fidaxomicin . although surgery seemed to be his best and possibly only option , his multiple co - morbidities , poor nutritional status , and deconditioning made his surgical risk prohibitively high , and colonic resection was deferred in light of relative clinical stability and no systemic signs to suggest toxicity . intravenous immunoglobulin ( ivig ) has shown promise in cases of severe refractory c. difficile colitis , ; thus , after failing all standard medical therapies , this patient was given ivig over 3  days ( gamunex - c 10% 1  g / kg on the first day , followed by 0.5  g / kg on the second and third days ) . three days after completing the ivig infusions , the frequency of bowel movements decreased to 35 times per day , and the patient reported significant improvement in his abdominal pain . repeat imaging with ct abdomen / pelvis on day 6 after receiving ivig demonstrated significant improvement in his colitis but with some residual disease in his right colon . due to concern for residual disease given these radiographic findings and persistent loose stools ( albeit less frequent ) , a  booster  dose of gamunex - c 10% 1  g / kg was given one week following the initial dose . no further radiographic evaluation was obtained until 3 months later when he was re - admitted for mrsa bacteremia likely secondary to an endovascular infection . at that time , he reported complete resolution of his abdominal pain and diarrhea , and his stool tested negative for c. difficile by pcr . follow - up imaging with ct of abdomen / pelvis showed no evidence of colitis or inflammation . in this case report , we described the successful treatment of severe refractory nap-1 pseudomembranous c. difficile colitis associated with megacolon using ivig . despite treatment with multiple medical modalities including fecal microbiota transplants and fidaxomicin , clinical and radiographic improvement was not observed until after administration of the immunoglobulin . the proposed mechanism of using ivig in clostridium difficile infections is inferred from the difference in the innate humoral immunity among asymptomatic and symptomatic colonizers . a prospective study of 271 hospitalized patients by kyne et al . showed a 48-fold increased likelihood of developing diarrhea if serum levels of anti - toxin a igg was 3.00 elisa units or less . for unclear reasons , the symptomatic colonizers seemed to be deficient in antibodies against toxin a , and thus , it is proposed that the pooled human immune gamma globulins provide passive immunity against this toxin . it remains unclear how ivig specifically works against the nap-1 strain of c. difficile . to our knowledge , this is the first case report of using ivig in a severe refractory clostridium difficile infection after failing fecal microbiota transplants and all medical treatments including fidaxomicin , and it adds to the growing evidence that ivig should be considered among the arsenal for fighting this debilitating and potentially life - threatening infection .
the mainstay treatment of clostridium difficile infections ( cdi ) is antimicrobials with growing support for fecal microbiota transplants . 
 we report the first case of an elderly man with severe refractory nap-1 pseudomembranous cdi who failed all medical therapy and two fecal transplants with response only seen after administration of intravenous immunoglobulin .