c. Difficile rev tables

Table 1. In Vitro Susceptibility of Clostridium difficile to Potential Therapeutic

Antimicrobial Agents (Data Selected from Representative Studies).

		MIC (mg/ml)
Agent	n	MIC₅₀	MIC₉₀	Range	Reference
Rifampin	55	< 0.001	0.002	<0.001-0.002	Bacon 1991 (8)
Metronidazole	50	0.29	0.6	0.25-1.0	Bannatyne 1987 (9)
Ramoplanin*	70	0.25	0.25	0.12-0.5	Biavsco 1991 (16)
Tiacumicin B* 15	15	0.25	0.25	0.12-0.5	Swanson 1991 (126)
Tiacumicin C*	15	0.5	1.0	0.25-1.0	Swanson 1991 (126)
Teicoplanin	70	0.5	0.5	0.25-1.0	Biavsco 1991 (16)
Vancomycin	70	1.0	2.0	1.0-2.0	Biavsco 1991 (16)
Tinidazole	50	0.55	3.74	0.5-4.0	Bannatyne 1987 (9)
Bacitracin	110	(MIC mode = 16 mg)		8.0-32.0	Young 1985 (144)
Fusidic Acid	20	(17/20 susceptible to 10 mg, disc testing)			Burdon 1979 (24)

* Investigational agents

Table 2. Randomized, Comparative Trials of Oral Therapy for Clostridium difficile Diarrhea* [Download PDF]

Table 3. Empirical Treatment Strategies for Patients with Multiple Recurrences of C. difficile Diarrhea

Strategy	References
Saccharomyces boulardii	McFarland 1994, Surawicz 1989, Surawicz 2000 (62, 81,82)
Lactobacillus GG	Biller 1995, Gorbach 1987 (10,38)
Rectal infusion of feces or a synthetic fecal bacterial flora	8 Reports summarized by Borody 2000 (19)
Oral infusion of donor stool via NG tube	Aas (3)
Administration of a non-toxigenic C. difficile strain	Seal 1987 (119)
Vancomycin and rifampin combination	Buggy 1987 (23)
Vancomycin in tapering doses/pulsed doses	Tedesco 1985 (89, 130)
Treatment with active agent followed by 2 week course of rifaximin	Johnson, CID 2007 (in press)
Intravenous gamma globulin	Hassett 1995, Warny 1995, Leung 1991, Wilcox 2004, McPherson 2006 (59, 77, 92, 137, 140)
Whole bowel irrigation	Liacouras 1996 (80); Persky 2000 (110)
No treatment with careful observation	Gerding 1995, Bartlett 1992 (6, 36)

Table 4. Empirical Treatment Protocol for Clostridium difficile-Infected Patients with Severe Ileus*

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Vancomycin 500 mg per rectum every 6 h^A, plus

Vancomycin 500 mg via NG tube every 6 h^B, plus

Metronidazole 500 mg IV every 6 h

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* Reference: 67

^ALiquid intravenous formulation diluted in 100 cc of normal saline: Insert #18 Foley catheter into rectum 4 to 8 inches,

fill the balloon to 30 cc, gently pull catheter down, instill vancomycin and clamp catheter for 60 minutes, deflate balloon

and remove catheter.

^BLiquid intravenous formulation diluted with at least 10 cc of fluid: clamp nasogastric tube for 60 minutes after each instillation.

Table 5. Potential Future Treatment Options

Product	Type	Stage of Development	Company	References
C. difficile vaccine	Vaccine	Phase I	Acambis	Sougioultzis
Monoclonal Antibody	Antibody	Phase II	Medarex	Gorbach
Nitazoxanide	Antibiotic	Phase III	Romark	Musher CID
Ramoplanin	Antibiotic	Phase III?	Oscient	Freeman JAC 2005
Rifaximin	Antibiotic	Phase III	Salix	Louie March
Tiacumicin b Complex (PAR-101, also known as OPT-80)	Antibiotic	Phase IIb	Optimer	Louie 2006 March, Ackerman AAC 2004
Tolevemar	Polymer	Phase III	Genzyme	Louie CID 2006

Figure 1: Three Hit Disease