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I enjoyed reading Kyne and Kelly's therapy update concerning treatments for recurrent Clostridium difficile diarrhoea (Gut 2001; 49:152–3). Recurrence after a single episode of diarrhoea can occur in up to 50% of cases1 and following recurrent bouts further relapse is even more likely. The authors have demonstrated that a serum antibody response to C difficile toxin A during an initial attack is associated with protection against recurrence1 and suggested that intravenous immunoglobulin may be useful in treating refractory recurrent disease. Here I report successful treatment of four adult patients with recurrent C difficile infection using intravenous immunoglobulin in order to increase the number of reported cases.
Case No 1
A 77 year old female with chronic obstructive pulmonary disease (COPD), heart failure, and non-insulin dependent diabetes mellitus (NIDDM) developed C difficile diarrhoea after treatment for pneumonia with ceftriaxone and clarithromycin. She had recurrence after each of two courses of metronidazole, a one week course, and a tapering course of vancomycin.2 Intravenous immunoglobulin (400 mg/kg) was administered and repeated after 21 days; a simultaneous tapering vancomycin course was given. Her diarrhoea quickly settled and there has been no recurrence over the ensuing 10 months.
Case No 2
A 75 year old female with COPD and NIDDM developed C difficile diarrhoea after treatment for pneumonia and cellulitis with ceftriaxone, clarithromycin, amoxicillin, and flucloxacillin. Diarrhoea recurred after courses of oral metronidazole, oral vancomycin, and tapering vancomycin. She was treated successfully with two infusions of immunoglobulin at a 21 day interval and tapering vancomycin. There has been no recurrence over eight months.
Case No 3
A 69 year old man underwent emergency repair of an abdominal aortic aneurysm. Perioperatively he received flucloxacillin, gentamicin, metronidazole, and ceftazidme. C difficile diarrhoea recurred after two separate courses of metronidazole and a further week of vancomycin. Diarrhoea resolved with intravenous immunoglobulin given as above and tapering vancomycin. There has been no recurrence after seven months.
Case No 4
An 82 year old female suffered a stroke. C difficile diarrhoea developed after treatment with ceftriaxone, metronidazole, and flucloxacillin for pneumonia and PEG site infection. Diarrhoea recurred after initial courses of metronidazole and vancomycin. Diarrhoea resolved with two infusions of immunoglobulin and tapering vancomycin. She was transferred to a nursing home and there has been no recurrence over five months.
Recurrence is commoner in older patients, those with comorbiidity, or those receiving multiple antibiotics.1 Failure to mount an immunoglobulin response to C difficile is associated with recurrence1 and Kyne and Kelly included passive immunisation with intravenous immunoglobulin among their options for treating recurrence. However, reports of successful use of immunoglobulin in this setting are few. Leung et al successfully treated five children with recurrent C difficile with immunoglobulin,3 and there is a single report of success in an adult with recurrent C difficile diarrhoea.4 Intravenous immunoglobulin has also been effective in two adult patients with severe acute refractory rather than recurrent disease.5 Normal pooled human immunoglobulin preparations contain significant titres of anti-C difficile antibodies.5 Although the number of reported patients is still small, it seems that immunoglobulin may be helpful for recurrent C difficile. The combination of two doses of immunoglobulin (400 mg/kg) with a tapering course of vancomycin produced lasting clearance of diarrhoea, even when diarrhoea had recurred after tapered vancomycin alone, suggesting the importance of the immunoglobulin. No complications of treatment were observed.
Intravenous immunoglobulin seems a promising adjunct in recurrent C difficile diarrhoea. I would agree with Kyne and Kelly that randomised controlled trials are needed to optimise the management of C difficile but such studies should include immunoglobulin.
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