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Metronidazole PO 400 mg (child: 10 mg/kg up to 400 mg) orally or via

nasogastric tube, 8-hourly for 10 days. May also be given intravenously in

patient unable to tolerate oral formulation at IV 500 mg TDS

Guidelines advocate metronidazole over vancomycin as first-line therapy [1,2, 7, 8].

Reasons included the lower cost of metronidazole relative to vancomycin and theequivalent clinical effectiveness in treating non-severe disease [9]. In addition,

use of metronidazole has been favored over vancomycin to limit the spread of

vancomycin-resistant enterococci.

SEVERE DISEASE

For severe disease (white cell count more than 15 x 109/L, severe abdominal

pain, elevated serum creatinine >1.5 x premorbid level, elevated serum lactate,

low serum albumin or organ dysfunction), Australian therapeutic guidelines [7]

recommend

vancomycin 125 mg (child: 3 mg/kg up to 125 mg) orally or via

nasogastric tube, 6-hourly for 10 days. IV vancomycin is not effective

against C difficile infection

Oral vancomycin is the preferred first-line therapy for severe cases of C. difficile

according the Australian, British and American therapeutic guidelines [1, 2, 7, 8].

Numerous studies have consistently demonstrated the superiority of oral

vancomycin in treatment of severe disease with the majority favouring its use for

all patients with severe and/or complicated disease [1, 10]. The major

pharmacologic advantage of vancomycin over metronidazole is that oral

vancomycin is not absorbed systemically, so maximal concentrations of the drug

can act intracolonically at the site of infection.

COMPLICATED DISEASE

In complicated cases (e.g. hypotension, shock, ileus, toxic megacolon),

Australian therapeutic guidelines [7] indicate:

metronidazole 500 mg (child: 12.5 mg/kg up to 500 mg) IV, 8-hourly plus

vancomycin 125 mg (child: 3 mg/kg up to 125 mg) orally or via

nasogastric tube, 6-hourly for 10 days.

Intra-colonic vancomycin may be useful in the setting of profound ileus that

impairs the delivery of orally administered drugs. In severe cases associated with

profound ileus, vancomycin can be administered as a retention enema (500 mg

in 100 mL sodium chloride 0.9% rectally, 6-hourly) in addition to oral or

nasogastric vancomycin and IV metronidazole.

Fulminant disease is underappreciated as a life-threatening disease because of a

lack of awareness of its severity and its non-specific clinical syndrome. Early

surgical referral is indicated in patients with severe disease and patientsdeveloping complications such as toxic megacolon, severe ileus, impending

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perforation, necrotizing colitis or systemic inflammatory response syndrome

leading to multi-organ system failure [11, 12]. Early diagnosis and treatment are

essential for a good outcome, and early surgical intervention should be used in

all patients unresponsive to medical therapy. Two surgical approaches for

management of CDI have been described [3]: subtotal colectomy and diverting

loop ileostomy with colonic lavage.

ALTERNATIVE THERAPIES Other therapeutic options for C. difficile infection

(CDI) are being developed. Alternative therapies that have been trialed include

probiotics and intravenous immunoglobulins [3] however studies have been

inconclusive regarding their benefits with no statistically significant difference in

clinical outcome.Faecal bacteriotherapy [13] ('stool transplant') appears to be

useful for intractable recurrent disease, but has considerable logistical issues.

[1] Cohen S, Gerding D, Johnson S, Kelly C, Loo V, McDonald L et al. Clinical

practice guidelines for Clostridium difficile infection in adults: 2010 update by

the society for healthcare epidemiology of America (SHEA) and the infectious

diseases society of America (IDSA). Infection Control Hospital Epidemiology.

2010 May; 31(5):p431-455

[2] Clostridium difficile-associated disease [monograph on the internet]. London:

BMJ Group; 2013 [cited 2013 March 20]. Available from:

http://bestpractice.bmj.com.acs.hcn.com.au/best-

practice/monograph/230/treatment.html

[3] Kelly C, LaMont T. Clostridium difficile in adults: Treatment. In: Basow D (Ed)

editor. Up-To-Date. Waltham MA: Wolter Kluwer Health; 2013

[4] McDonald J. Prevention and control of Clostridium difficile in hospital and

institutional settings. In: Basow D (Ed) editor. Up-To-Date. Waltham MA: Wolter

Kluwer Health; 2013

[5] Stuart R, Marshall C, McLaws M, Boardman C, Russo P, Harrington G et al.

ASID/ AICA position statement - Infection control guidelines for patients with

Clostridium difficile infection in healthcare settings. Healthcare Infection. 2011

March 28; 16(1):p33-39

[6] Siegel J, Rhinehart E, Jackson M, Chiarello L. Healthcare Infection ControlPractices Advisory Committee 2007 Guideline for Isolation Precautions:

Preventing Transmission of Infectious Agents in Healthcare Settings. Atlanta:

Centers for Disease Control and Prevention; 2007 June; cited 2013 March 20.

Available from:

http://www.cdc.gov/hicpac/pdf/isolation/Pages1_3_Isolation2007.pdf

[7]Electronic therapeutic guidelines. Clostridium difficile infection. Melbourne:

Therapeutic Guidelines Limited; 2012 November; cited 2013 March 20. Available

from: http://etg.hcn.com.au

[8]Cheng A, Ferguson J, Richards M, Robson J, Gilbert G, McGregor A et al.Australasian Society for Infectious Disease guidelines for the diagnosis and

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