Management of inflammatory bowel disease with Clostridium difficile infection

Table 1 Epidemiology of Clostridium difficile infection in inflammatory bowel disease

Ref.	Patient population	Sampling time frame	Diagnosis method	Disease activity	Conclusions
Keighley[92] (1983)	IBD adult inpatients	1978-1980	Stool culture on selective medium + cytotoxicity assay	Active	CDI incidence (%) IBD: 5.7; UC 4.7; CD 6.3
Gurian et al[93] (1983)	IBD adult inpatients and outpatients	1980-1981	Stool culture on selective medium + cytotoxicity assay	Active	CDI incidence (%) IBD: 0
Rolny et al[26] (1983)	IBD adult inpatients	1980-1981	Stool culture on selective medium + cytotoxicity assay	Active	CDI incidence (%) UC: 5; CD: 7.7
Greenfield et al[21] (1983)	IBD adult inpatients and outpatients	1980-1981	Stool culture on selective medium + cytotoxicity assay	Mixed	CDI incidence (%) UC: 13.7; CD: 13.2
Burke et al[94] (1987)	IBD adult outpatients	1984-1986	Stool culture on selective medium + cytotoxicity assay	Active	CDI incidence (%) IBD 3.2
Gryboski[95] (1991)	IBD pediatric inpatients and outpatients	1986-1990	Stool culture on selective medium + cytotoxicity assay	Active	CDI incidence (%) IBD 16; UC: 18; CD 14
Meyer et al[22] (2004)	IBD adult inpatients and outpatients	2000-2001	Immunoassay for Toxin A until 2001 then EIA for Toxin A/B	Active	CDI incidence (%) IBD: 16.7; UC: 12.5; CD: 23.8; IC: 11.1
Mylonaki et al[23] (2004)	IBD adult inpatients and outpatients	1997-2001	ELISA for Toxins A/B	Active	CDI incidence (%) IBD: 5.5; CD: 13.2
Issa et al[24] (2007)	IBD adult inpatients and outpatients	2005	ELISA for Toxins A/B	Active	CDI incidence (%) UC: 6.1; CD: 4.1
					IBD patients accounted for 4% of the total CDI patient cohort in 2003, 7% in 2004, and 16% in 2005
Rodemann et al[16] (2007)	IBD pediatric and adult inpatients (United States)	1998-2004	Cell cytotoxic culture	Active	CDI incidence (%) UC: 3.9; CD: 1.6
			2002 onwards C. difficile Toxin A/B immunoassay		CDI incidence increase: UC > CD > non-IBD
					Non-IBD population: 8.5 to 15.9/1000 admissions
					CD: 9.5 to 22.3/1000 admissions
					UC: 18.4 to 57.6/1000 admissions
Shen et al[33] (2008)	UC adult outpatients with IPAA	2005-2006	ELISA for Toxin A/B	Mixed	CDI incidence (%) UC: 18.3
Bossuyt et al[20] (2009)	IBD and non-IBD CDI adult inpatients	2000-2008	EIA for Toxin A until 2005, then EIA for Toxins A/B	Active	All patients: 3.75-fold increase in CDI between 2000-2003 and 2004-2008
Balamurugan et al[96] (2008)	UC adult outpatients	2004-2005	PCR for C. difficile	Mixed	CDI incidence (%) UC: 92
			Toxin A/B ELISA
Ananthakrishnan et al[18] (2008)	IBD and non-IBD CDI adult inpatients	1998-2004	N/R	N/R	CDI incidence increase: UC: 24 to 39/1000 discharge ; CD: 8 to 12/1000 discharges
Nguyen et al[17] (2008)	IBD and non-IBD adult inpatients	1998-2004	N/R	N/R	CDI incidence increase: UC: 26.6 to 51.2/1000 discharges
Pascarella et al[35] (2009)	IBD pediatric inpatients	2005-2007	Enzyme immunoassay for toxins A/B	Mixed	CDI incidence (%) UC: 21.3; CD: 35
Ricciardi et al[27] (2009)	IBD adult inpatients	1993-2003	N/R	Active	CDI incidence (%) UC: 2.8; CD: 1.0
					CDI incidence increase: IBD: 12.2 to 21/1000 discharges; CD + colonic involvement: 12.2 to 23.1/1000 discharges
Wultańska et al[36] (2010)	IBD pediatric outpatients	2005-2007	EIA for Toxins A/B	Mixed	CDI incidence (%) IBD: 60; UC: 61; CD: 59
			or PCR
Ananthakrishnan et al[58] (2011)	IBD adult inpatients	1998, 2004, 2007	N/R	N/R	CDI incidence increase: CD: 0.8 to 1.5% of hospitalizations; UC: 2.4 to 5.3% of hospitalizations
					Absolute mortality increase in CDI + IBD (5.9% to 7.2%)
Kaneko et al[46] (2011)	UC pediatric and adult inpatients and outpatients	2006-2009	ELISA for Toxin A	Active	CDI incidence (%) UC inpatient: 36.6; UC outpatient: 41.7
Mezoff et al[37] (2011)	IBD pediatric patients	2007-2008	EIA for Toxins A and B	Mixed	CDI incidence (%) UC: 5.8; CD: 7.8; IC: 11.1
Ott et al[28] (2011)	IBD adult inpatients	2001-2008	ELISA for Toxins A/B or characteristic histology	Active	CDI incidence (%) IBD: 4.0; CD: 13.2; UC: 4.7
Banaszkiewicz et al[38] (2012)	IBD pediatric inpatients	2007-2010	EIA for Toxins A and B	Mixed	CDI incidence (%) IBD: 47
Antonelli et al[29] (2012)	IBD adult inpatients	2007-2010	N/R	Active	CDI incidence (%) UC: 11.1; CD: 1.7
Murthy et al[31] (2012)	UC adult inpatients	2002-2008	N/R	Active	CDI incidence (%) UC: 9.0
Lamousé-Smith et al[97] (2013)	IBD pediatric inpatients and outpatients (United States)	2006-2012	PCR for Toxin B +/- ELISA for Toxin A/B	Mixed	CDI incidence (%) UC: 18.4; CD: 11.6
Masclee et al[47] (2013)	IBD adult outpatients	2009-2010	PCR for C. difficile and Toxin A/B	Active	CDI incidence (%) IBD: 4.9; UC: 3.4; CD: 5.9
Mir et al[39] (2013)	IBD pediatric patients	2010-2012	EIA or PCR for Toxin A/B	N/R	CDI incidence (%) IBD: 8.1; UC: 5.6; CD: 9.3 ; IBDU: 11.1
					No significant variation in IBD incidence over 3 yr
Pant et al[98] (2013)	IBD pediatric inpatients	2000, 2003, 2006, 2009	N/R	N/R	CDI incidence increase: IBD: 21.7 to 28 cases/1000 IBD cases per year; UC: 28.1 to 42.2/1000 cases per year; CD: 18.3 to 20.3/1000 cases per year
Li et al[34] (2013)	IBD adult outpatients with IPAA	2010-2011	PCR for Toxin B gene	Active	CDI incidence (%) IBD: 10.7; UC: 10.4; CD: 0; IC: 25.0
Martinelli et al[40] (2014)	IBD pediatric inpatients and outpatients	2010-2011	EIA for Toxins A/B	Mixed	CDI incidence (%): IBD: 10.0; UC: 7.5; CD: 11.9
Regnault et al[30] (2014)	IBD adult inpatients	2008-2010	Stool culture on selective medium + cytotoxicity assay +/- toxigenic culture	Active	CDI incidence (% hospitalizations): IBD: 7.0; UC: 6.8; CD: 7.2
Negrón et al[32] (2014)	UC adult inpatients	2000-2009	EIA for Toxins A/B	Active	CDI incidence (%) UC: 6.1
Hourigan et al[99] (2014)	IBD and non-IBD pediatric and adult inpatients	1993-2012	N/R	N/R	CDI incidence increase: IBD: 19.9 to 67/1000 admissions
					Rate of increase in CDI not significantly different between patients with or without IBD
Krishnarao et al[25] (2015)	IBD adult inpatients and outpatients	2008-2011	EIA and PCR	Mixed	CDI incidence (%) IBD: 5.1
Sandberg et al[19] (2015)	IBD pediatric inpatients	1997-2011	N/R	N/R	Hospitalization rate increase: CDI + IBD: 2.8 to 14.4 per million population per year
					Rate of increase for UC + CDI = CD + CDI
Simian et al[100] (2016)	IBD adult and pediatric inpatients and outpatients	2014-2015	PCR	N/R	CDI incidence (%) UC: 5.0; CD: 5.0
Roy et al[101] (2016)	CD adult outpatients on chronic antibiotic therapy > 6 mo	1992-2015	N/R	N/R	CDI incidence (%) CD: 2.0

IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s Disease; IC: Indeterminate colitis; IBDU: Inflammatory bowel disease unclassified; IPAA: Ileal anal-pouch anastomosis; EIA: Enzyme immunoassay; ELISA: Enzyme linked immunosorbent assay; PCR: Polymerase chain reaction ; N/R: Not reported.

Table 2 Risk factors for Clostridium difficile infection in inflammatory bowel disease

Ref.	Sampling time frame	Setting	Diagnosis method	Identified risk factors
				HOST	ENVIRONMENT
Razik et al[44] (2016)	2010-2013	Inpatient	PCR	Non-ileal CD	Hospitalisation for CDI; recent antibiotic use; biologic therapy; 5-ASA; Steroids
McCurdy et al[54] (2016)	2005-2011	Inpatient and outpatient	PCR	CMV infection	N/A
Seril et al[45] (2014)	2010-2013	Inpatient and outpatient	PCR for Toxin B	Post-surgery mechanical intestinal complications; low serum immunoglobulin level	None identified
Regnault et al[30] (2014)	2008-2010	Inpatient	Stool culture on selective medium + cytotoxicity assay +/- toxigenic culture	None identified	NSAIDs
Connelly et al[52] (2014)	N/R	N/R	PCR for Toxin A gene	IL-4 gene associated SNP rs2243250	Not studied
Ananthakrishnan et al[102] (2014)	1998-2010	Inpatient	N/R	Low vitamin D concentration	Not studied
Ananthakrishnan et al[56] (2013)	N/R	Inpatient and outpatient	ELISA for Toxin A/B	Female sex; pancolitis; IBD-related SNPs	Protective : Anti-TNF therapy
Monaghan et al[53] (2013)	2009-2012	N/R	Toxigenic culture	Impaired ability to generate: toxin-specific antibody, memory B-cell responses	Not studied
Li et al[34] (2013)	2010-2011	Outpatient	PCR for Toxin B	None identified	Recent hospitalization
Masclee et al[47] (2013)	2009-2010	Outpatient	PCR for C. difficile and Toxins A/B	None identified	None identified
Kaneko et al[46] (2011)	2006-2009	Inpatient and outpatient	ELISA for Toxin A	None identified	None identified
Kariv et al[43] (2011)	2000-2006	Inpatient and outpatient	EIA for Toxin A/B	Recent surgery	Recent antibiotic use; recent hospitalization
Ricciardi et al[27] (2009)	1993-2003	Inpatient	N/R	Colonic involvement	Not studied
Schneeweiss et al[49] (2009)	2001-2006	Inpatient and outpatient	N/R	Not studied	Corticosteroid initiation
Nguyen et al[17] (2008)	1998-2004	Inpatient	N/R	Colonic involvement	Not studied
				Comorbidity
Issa et al[24] (2007)	2005	Inpatient	ELISA for Toxin A/B	Colonic involvement	Maintenance immunomodulator use
Rodemann et al[16] (2007)	1998-2004	Inpatient	Cell cytotoxic culture	Age	Not studied
			2002 onwards C. difficile Toxin A/B immunoassay	Comorbidity
Mylonaki et al[23] (2004)	1997-2001	Inpatient	ELISA for Toxin A/B	None identified	Recent antibiotic use

CDI: Clostridium difficile infection; rCDI: Recurrent Clostridium difficile infection; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s Disease; IPAA: Ileal anal-pouch anastomosis; CMV: Cytomegalovirus; CF: Cystic fibrosis; EIA: Enzyme immunoassay; ELISA: Enzyme linked immunosorbent assay; NSAID: Non-steroidal anti-inflammatories PCR: Polymerase chain reaction; N/R: Not reported.

Table 3 Outcomes of inflammatory bowel disease patients with Clostridium difficile infection

Ref.	Patient population	Sampling time frame	Study design	n	Outcomes
Razik et al[44] (2016)	Adult CDI	2010-2013	Retrospective, single-center, cohort study	503	Incidence of rCDI
	IBD + CDI				IBD > non-IBD [2.04/100 person-months (95%CI: 1.55-2.64) vs 1.25 episodes per 100 person-months (95%CI: 1.05-1.48)]
	Inpatient				Colectomy
					IBD > non-IBD (6.4% vs 0.3%)
Skowron et al[61] (2016)	Adult IBD + IPAA	2000-2010	Retrospective, observational, single-center cohort study	417	CDI pre-colectomy associated with post-reconstruction pouch failure (HR = 3.02 95%CI: 1.23-7.44)
	Inpatient (United States)
McCurdy et al[54] (2016)	Adult IBD	2005-2011	Retrospective, case-control, single-center, study	248	Colectomy-free survival at 1 yr
	IBD + CMV				IBD + CDI > IBD + CMV + CDI (71.5% vs 30%)
	IBD + CMV + CDI				IBD + CMV controls > IBD + CMV + CDI (57.1% vs 30%)
	IBD + CDI
	Inpatient and outpatient (United States)
Negrón et al[32] (2014)	Adult UC	2000-2009	Retrospective, case-control, multi-center, database study	481	Emergent surgery
	Inpatient (Canada)				CDI + UC > UC alone [OR = 3.39 (95%CI: 1.02-11.23)]
					Development of new infectious postoperative complication
					CDI + UC > UC alone (OR = 4.76, 95%CI: 1.10-20.63)
Horton et al[70] (2014)	Adult IBD	2006-2010	Retrospective, observational, single-center study	114	Readmission:
	Inpatient (United States)				UC + CDI > CD + CDI (24% vs 10%, P = 0.04)
					IBD + steroids > no-steroids (29% vs 8%, P < 0.01)
					Colectomy:
					UC + CDI > CD + CDI, index admission (27.4% vs 0%, P < 0.01)
					IBD + steroids > no-steroids (32% vs 6%, P < 0.01)
Pant et al[98] (2013)	Pediatric IBD	2000, 2003, 2006, 2009	Retrospective, nested case-control, nationwide database study	12610	LOS:
	Inpatient (United States)				CDI + IBD > IBD (8.0 vs 6.0, aRC = 2.1 d, 95%CI: 1.4-2.8)
					Hospitalization cost:
					CDI + IBD > IBD alone ($45126 vs $34703, aRC = $11506, 95%CI: 6192-16829)
					Parenteral nutrition:
					CDI + IBD > IBD alone (15.9% vs 12.1% aOR = 1.5, 95%CI: 1.1-2.0)
					Blood transfusions:
					CDI + IBD > IBD alone (17.7% vs 9.8%, aOR = 1.8, 95%CI: 1.4-2.4).
Li et al[34] (2013)	Adult IBD + IPAA	2010-2011	Prospective, single-center, cohort study	196	42.9% cured by single course of Vancomycin
	Outpatient (United States)				57.1% recurrent/refractory CDI
Chu et al[103] (2013)	Adult UC + CDI	2002-2012	Retrospective, single-center, observational study	23	Morbidity and mortality after colectomy:
	Inpatient (United States)				UC + CDI + full antibiotic course pre-op = UC + CDI + incomplete antibiotic course pre-op
Ananthakrishnan et al[55] (2013)	Adult IBD	2007	Retrospective, nested case-control, nationwide database study	67221 hospitalizations	Mortality:
	Inpatient (United States)				CDI + IBD vs IBD alone (OR = 3.23, 95%CI: 2.55-4.03).
Murthy et al[31] (2012)	Adult UC	2002-2008	Retrospective, database, cohort study	2016	Mortality:
	Inpatient (Canada)				CDI + UC > UC alone, 5-yr risk (aHR = 2.40, 95%CI: 1.37-4.20)
					CDI + UC > UC alone, index hospitalization (aHR = 8.90, 95%CI: 2.80-28.3)
					CDI + UC > UC alone, 5 years post-discharge (aHR = 2.41, 95%CI: 1.37-4.22)
Navaneethan et al[60] (2012)	Adult UC	2002-2007	Retrospective, single-center, cohort study	146	UC-related ER visits:
	Inpatient and outpatient (United States)				CDI + UC vs UC alone, 1 yr post index infection (37.8% vs 4%, P < 0.001)
					Colectomy:
					CDI + UC vs UC alone, 1 yr post index infection (35.6% vs 9.9%, P < 0.001)
					CDI associated with colectomy within 1 yr (OR = 10, 95%CI: 2.7-36.3)
					Escalation in therapy:
					CDI + UC year after CDI admission vs year prior (55.8% vs 12.9%, P < 0.0001)
Jen et al[57] (2011)	Adult IBD	2002-2008	Retrospective, nested case-control, nationwide database study	241478 hospitalizations	Mortality:
	Inpatient (England)				IBD + CDI (defined as hospital-acquired > IBD alone (aOR = 6.32, 95%CI: 5.67-7.04)
					LOS:
					IBD + CDI > IBD alone (27.9 d longer)
					GI surgery:
					IBD + CDI > IBD alone (aOR = 1.87, 95%CI: 0.60-5.85)
Kariv et al[43] (2011)	Adult UC	2000-2006	Single-center	78	Colectomy within 3 mo not associated with CDI
	Inpatient and outpatient (United States)				No UC or CDI associated mortality identified
Ananthakrishnan et al[58] (2011)	Adult IBD	1998, 2004, 2007	Retrospective, nested case-control, nationwide database study	-	Mortality:
	Inpatient (United States)				IBD + CDI > IBD alone, from 1998 to 2007 (OR = 2.38, 95%CI: 1.52-3.72 to OR = 3.38, 95%CI: 2.66-4.29).
Kelsen et al[62] (2011)	Pediatric IBD	1997-2007	Retrospective, nested case-control, single-center study	315	rCDI:
	Inpatient (United States)				CDI + IBD > CDI-alone (34% vs 7.5%, P < 0.0001)
					Escalation in therapy:
					IBD + CDI > IBD alone (67% vs 30%, P < 0.001)
Jodorkovsky et al[59] (2010)	Adult UC	2004-2005	Retrospective, single-center, case-control study	99	UC-related hospitalizations:
	Inpatient (United States)				CDI + IBD > IBD alone, over 1 yr
					Colectomy:
					CDI at index admission predictor for colectomy within 1 yr (OR = 2.38, 95%CI: 1.01-5.6)
					CDI status not a significant predictor for requirement for emergent colectomy at index admission
					LOS:
					CDI + IBD = IBD alone
Ben-Horin et al[64] (2010)	Adult IBD + CDI	2000-2008	Retrospective, multi-center, cohort study	93	Morbidity and mortality:
	Inpatient (Europe/Israel)				IBD + CDI patients + pseudomembranes on endoscopy = IBD + CDI without pseudomembranes
Nguyen et al[17] (2008)	IBD and non-IBD controls	1998-2004	Retrospective, nested case-control, nationwide database study	116842 hospitalizations	Mortality:
	Inpatient (United States)				UC + CDI > CDI alone (OR = 3.79, 95%CI: 2.84-5.06)
					LOS:
					CD + CDI > CDI alone
					Hospitalization cost:
					UC + CDI > CDI alone

CDI: Clostridium difficile infection; rCDI: Recurrent clostridium difficile infection; IBD: Inflammatory bowel disease; UC: Ulcerative colitis; CD: Crohn’s disease; IPAA: Ileal anal-pouch anastomosis; CMV: Cytomegalovirus; OR: Odds ratio; aOR Adjusted odds ratio; aRC: Adjusted regression coefficient; LOS: Length of stay.

Table 4 Treatment of clostridium difficile infection in inflammatory bowel disease[3,4]

Severity	Criteria	Treatment	Comments
First episode
Stop all non-CDI related antibiotic therapy if possible
Mild to moderate disease	Diarrhea and symptoms not meeting criteria for severe disease	Metronidazole 500 mg by mouth 3 times per day for 10 d to 14 d	In hospitalized patients with UC and nonsevere CDI, treatment with a vancomycin-containing regimen vs metronidazole alone resulted in fewer readmissions and shorter LOS[70]
		or
		Vancomycin 125 mg by mouth 4 times per day for 10 to 14 d
Severe disease	Serum albumin < 3 g/dL AND one of the following:	Vancomycin 125 mg by mouth 4 times per day for 10 to 14 d
	WBC ≥ 15000 cells/mm3
	Abdominal tenderness
	Creatinine ≥ 133 μmol/L
Severe, complicated disease	Admission to intensive care unit	Vancomycin 500 mg by mouth or nasogastric tube 4 times per day	Consider early surgical consultation
	Hypotension ± vasopressor requirement	and
	Fever ≥ 38.5 °C	Metronidazole 500 mg IV every 8 h
	Ileus	and, if ileus,
	Mental status changes	Vancomycin 500 mg in 500 mL saline as enema 4 times per day
	WBC ≥ 35000 cells/mm3 or ≤ 2000 cells/mm3
	Serum lactate ≥ 2.2 mmol/L
	End organ failure
Recurrent CDI
First recurrence		Metronidazole 500 mg by mouth 3 times per day for 10 to 14 d
		or
		Vancomycin 125 mg by mouth 4 times per day for 10 to 14 d
		or
		Fidaxomicin 200 mg by mouth 2 times per day for 10 d
Second recurrence		-Tapered and pulsed vancomycin
		or
		Fidaxomicin 200 mg by mouth 2 times per day for 10 d
Subsequent recurrence		-Fecal microbiota transplant

LOS: Length of stay; CDI: Clostridium difficile infection; UC: Ulcerative colitis.

Table 5 Case reports of corticosteroid initiation in Clostridium difficile infection

Reference (year of publication)	Patient data		Treatment regimen	Outcome
	Demographics	Clinical presentation
Cavagnaro et al[104] (2003)	5M	Bloody diarrhea (> 10 loose stools/d), tenesmus, abdominal tenderness, fever	Oral vancomycin (40 mg/kg per day divided in 6-hourly doses) and IV metronidazole (20 mg/kg per day divided in 8-hourly doses) × 14 d	Resolution of diarrhea within 24 h of steroid initiation
		WBC 19000 cells/mm3, albumin 21 g/L		Resolution of endoscopic changes at 6 wk
		Positive C. difficile toxin	IV methyldrnisolone (2 mg/kg per day in two divided doses) on day 14 × 3 d
		Pseudomembranous colitis on flexible sigmoidoscopy on day 14	Prednisone 2 mg/kg per day tapered over one month
Sykes et al[105] (2012)	54F	Moderate CDI that resolved with 10-d course antibiotics	Oral metronidazole × 10 d with resolution of symptoms (doses not specified)	Decreased stool frequency, normalization of vital signs, reduction in CRP to 132 within 48 h of steroid initiation
		Recurrent diarrhea and abdominal pain 10 d after completion of antibiotics with		Resolution of diarrhea, further reduction in CRP to 15 after 9 d of steroid therapy
		left colonic thickening on CT and positive C. difficile toxin	Oral vancomycin and metronidazole upon admission (doses not specified) × 4 d	Resolution of endosocopic changes at 1 mo
		Fever, tachycardia on day 4		Sustained clinical response at 5 mo
		with pseudomembranous colitis on flexible sigmoidoscopy	Oral vancomycin 125 mg every 6 h × 9 d
		CRP increased from 149 on admission to 236 on day 4	IV hydrocortisone 100 mg every 6 h × 9 d
			Prednisolone 30 mg daily with tapering regimen
	73F	Moderate-severe CDI that resolved with 10-d course antibiotics	Metronidazole 400 mg every 8 h × 10 d with resolution of symptoms	Resolution of diarrhea, normalization of vital signs, reduction in CRP to 7 within 48 h of steroid initiation
		Recurrent moderate CDI 1 wk after completion of antibiotics that resolved with another 10-d course of antibiotics		Complete clinical response at 14 d with no further relapses
		Recurrent CDI 10 d after completion of antibiotics with fever, tachycardia, increased CRP 87	Oral vancomycin 125 mg every 6 h × 10 d with resolution of symptoms
		Slow response to antibiotics with flexible sigmoidoscopy on day 8 with pseudomembranous colitis
			Oral vancomycin 125 mg every 6 h × 8 d with tapering regimen over 14 d
			Prednisolone 30 mg daily × 7 d followed by tapering regimen
	91F	Moderate CDI with persistent diarrhea despite courses of metronidazole and vancomycin	Oral metronidazole 400 mg every 8 h × 10 d without resolution of symptoms	Resolution of diarrhea and normalization of CRP within 72 h of steroid initiation
		CRP 11		No further relapses
		Flexible sigmoidoscopy with pseudomembranous colitis	Oral vancomycin 125 mg every 6 h for prolonged course without resolution of symptoms
			Prednisolone 30 mg daily × 14 d with continued vancomycin tapering regimen over 4 wk

CDI: Clostridium difficile infection; CRP: C-reactive protein.