Keywords: C. Difficile, Relapsing Clostridium Difficile Associated Diarrhea, intravenous immunoglobulin, Vancomycin

Introduction

Clostridium Difficile is responsible for the majority of hospital-acquired infectious diarrhea in developed countries. Clostridium Difficile (CD) is part of the normal flora of approximately 2% of asymptomatic healthy adults. Prevalence increases with age and the elderly have colonization rates of up to 14% [1, 2]. Symptoms can vary from mild diarrhea to severe necrotizing colitis and toxic megacolon. The initial step in management is withdrawal of precipitant antibiotics when feasible in addition to oral metronidazole (Preferred first line drug) or vancomycin for 7-10 days. Symptomatic relapse occurs in up to 20% patients after completion of therapy [3]. Intravenous immunoglobulin (IVIG) usage in Clostridium Difficile Associated Diarrhea (CDAD) may be decreases the incidence of morbidity, mortality, colectomies and hospital stay.

Case Report

A 72 year old woman with medical history of HTN, DM, multiple episodes of clostridium difficile colitis and hypothyroidism presented with complaint of abdominal pain. Patient was discharged from our hospital three weeks ago after being treated for an episode of C.difficile colitis. Work up during that episode revealed pancolitis on CT Abdomen/Pelvis and psudomembranous colitis on sigmoidoscopy. She was started on metronidazole then subsequently discharged on tapering vancomycin due to persistent diarrhea. She completed the vancomycin 5 days prior to this admission. Presently the abdominal pain was diffuse, 5/10 intensity, colicky, intermittent and associated with tactile fever and green soft stools, ten/day. On admission Vitals: T-max 101.9, Pulse 120, RR 20, BP 94/60. Examination: mildly distended abdomen with tenderness in lower quadrants. Patient was admitted with the impression of relapsing clostridium difficile colitis. Stool workup was sent and she was started on oral vancomycin.  C. Difficile toxin A tested positive. Patient was started on vancomycin, rifampin and cholestyramine. One week after initiation of treatment, she continued to have diarrhea, abdominal pain and fever. Treatment was changed to saccharomyces boulardii, metronidazole, vancomycin and rifampin. Despite the treatment, she still had diarrhea with abdominal distension. A single dose of IVIG was given with symptomatic improvement. She was discharged on tapering vancomycin dose for 5 weeks. Patient has been symptom free since discharge.

C. Difficile Toxin In stool

Laboratory Workup

CT Abdomen/Pelvis C+ showing Pancolitis

Discussion

C. Difficile Associated Diarrhea (CDAD) cases are defined as patients with diarrhea (at least three loose stools per day) for at least 2 days with cytotoxin-positive feces [4]. Once C. Difficile colonizes the gut the spores can vegetate, multiply and secrete toxin A (cytotoxin and entrotoxin) and toxin B (cytotoxin), causing diarrhea and psudomembranous colitis. Recurrent CDAD is difficult to manage since repeated antibiotic exposure may exacerbate gut flora disturbance [3, 4]. Relapse often occur within one to two weeks of discontinuing therapy but can be seen up to two months. Passive immunotherapy with IVIG may be a useful addition to antibiotic therapy for severe, refractory CDAD [5]. There are no controlled studies of IVIG with a tapering course vancomycin therapy in CDAD. It is believed that tapering vancomycin works by killing germinated C. Difficile bacteria. The precise mechanism of action of IVIG is not entirely clear since to be effective, IgG antitoxin must leave the circulation and bind to toxins A and B within the intestinal lumen. The presence or absence of an adequate antibody response to C.difficile toxins is believed to play an important role in determining the severity of diarrhea and colitis [6]. Patients with low antitoxin levels are reported to have more severe, prolonged or recurrent CDAD whereas asymptomatic carriers have higher antitoxin levels. Severe, unresponsive psudomembranous colitis may result in colonic perforation, septicemia, and death. Colectomy may be life saving in these circumstances but patients who are surgically unfit may benefit from a trial of IVIG [7]. Although the number of reported patients is still small, it appears that immunoglobulin may be helpful for recurrent CDAD. In our patient, the combination of immunoglobulin with a tapering course of vancomycin appeared superior to tapered vancomycin alone.

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