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. 1997 Sep;41(3):366–370. doi: 10.1136/gut.41.3.366

Intravenous immunoglobulin therapy for severe Clostridium difficile colitis

J Salcedo 1, S Keates 1, C Pothoulakis 1, M Warny 1, I Castagliuolo 1, J LaMont 1, C Kelly 1
PMCID: PMC1891485  PMID: 9378393

Abstract

Background—Many individuals have serum antibodies against Clostridium difficile toxins. Those with an impaired antitoxin response may be susceptible to recurrent, prolonged, or severe C difficile diarrhoea and colitis. 
Aims—To examine whether treatment with intravenous immunoglobulin might be effective in patients with severe pseudomembranous colitis unresponsive to standard antimicrobial therapy. 
Patients—Two patients with pseudomembranous colitis not responding to metronidazole and vancomycin were given normal pooled human immunoglobulin intravenously (200-300 mg/kg). 
Methods—Antibodies against C difficile toxins were measured in nine immunoglobulin preparations by ELISA and by cytotoxin neutralisation assay. 
Results—Both patients responded quickly as shown by resolution of diarrhoea, abdominal tenderness, and distension. All immunoglobulin preparations tested contained IgG against C difficile toxins A and B by ELISA and neutralised the cytotoxic activity of C difficile toxins in vitro at IgG concentrations of 0.4-1.6 mg/ml. 
Conclusion—Passive immunotherapy with intravenous immunoglobulin may be a useful addition to antibiotic therapy for severe, refractory C difficile colitis. IgG antitoxin is present in standard immunoglobulin preparations and C difficile toxin neutralising activity is evident at IgG concentrations which are readily achieved in the serum by intravenous immunoglobulin administration. 



Keywords: Clostridium difficile; toxin; diarrhoea; IgG; immunotherapy; antibiotic

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Figure 1 .

Figure 1

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: Computed tomogram of the abdomen of patient 1 showing dilated loops of colon (A) and the presence of ascitic fluid (B). 


Figure 2 .

Figure 2

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: Plain abdominal radiograph of patient 2 showing colonic dilatation and thickening of the colonic wall consistent with notable mucosal oedema (A). Photomicrograph of sigmoidoscopic biopsy specimen showing acutely inflamed colonic mucosa and an overlying pseudomembrane (B). 


Figure 3 .

Figure 3

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: C difficile antitoxin activity in human immunoglobulin preparations. (A) Anti-C difficile culture filtrate IgG levels measured by ELISA in commercially available pooled normal human immunoglobulin preparations. Three lots from each of three suppliers were studied (Alpha Therapeutic Corporation (open triangle), Armour Pharmaceutical Company (open square), and Baxter Healthcare Corporation (open circle). (B) IgG levels against C difficile culture filtrate (open circle), toxin A (open triangle), and toxin B (open square) in a representative immunoglobulin preparation (denoted by the arrow in A). 


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