Clinical update for the diagnosis and treatment of Clostridium difficile infection

Table 1 Characteristics of tests for Clostridium difficile infections

	Sensit-ivity	Detects toxin in stool	Time totest completion	Cost	Availability	Standalonetest
EIA Toxin A/B	++	Yes	h	+	++++	Yes
GDH1	++++	No5	h	+	++++	No
PCR2	+++	No6	h	++++	+++	Yes
TC3	+++++	No6	d	+++	+7	Yes
CCCNA4	+++	Yes	d	+++	+7	Yes

¹Glutamate dehydrogenase;

²Polymerase chain reaction;

³Toxigenic culture;

⁴Cell culture cytotoxicity neutralization assay;

⁵Detects presence of Clostridium difficile (C. difficile I) only, but not toxin producing capability, requires confirmatory testing;

⁶Detects toxin producing C. difficile, but not toxin in stool, false (+) in asymptomatic carriers;

⁷Only available in research laboratory. EIA: Enzyme immunoassay; GDH: Glutamate dehydrogenase; PCR: Polymerase chain reaction; TC: Toxigenic culture; CCCNA: Cell culture cytotoxicity neutralization assay.

Table 2 Comparison of American College of Gastroenterology 2013 and Society for Healthcare Epidemiology of America/Infectious Diseases Society of America 2010 Guidelines for Treatment of Clostridium difficile infection (Differences between the guidelines are in bold)

	SHEA/IDSA 20101		ACG 20132
Severity	Definition	Treatment	Definition	Treatment
Mild-to- Moderate	WBC < 15000 cells/μL or lower and serum Cr < 1.5 times the premorbid level	Metronidazole 500 mg 3 times/d by mouth for 10-14 d	Diarrhea plus any additional signs or symptoms not meeting severe or complicated criteria	Metronidazole 500 mg orally 3 times/d for 10 d. If no improvement in 5-7 d, consider change to vancomycin at standard dose.
Severe	WBC > 15000 cells/μL or higher or a serum Cr > or equal to 1.5 times the premorbid level	Vancomycin 125 mg 4 times/d by mouth for 10-14 d	Serum albumin < 3 g/dL plus one of the following: WBC ≥ 15000 or abdominal tenderness	Vancomycin 125 mg orally 4 times/d by mouth for 10 d
Severe, complicated	Hypotension or shock, ileus, megacolon	Vancomycin 500 mg four times/d by mouth or by nasogastric tube, plus metronidazole 500 mg every 8 h intravenously. If complete ileus, consider adding rectal installation of vancomycin	Any of the following attributable to CDI: ICU admission, hypotension with or without the need for vasopressors, fever ≥ 38.5 °C, ileus or significant abdominal distension, mental status changes, WBC > 35000 cells/mm3 or < 2000 cells/mm3, serum lactate > 2.2 mmol/L, end organ failure	Vancomycin 500 mg orally four times/d and metronidazole 500 mg IV every 8 h and vancomycin per rectum (500 mg in 500 mL saline as enema) four times a day

¹Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA)[31];

²American College of Gastroenterology (ACG)[71].WBC: white blood cell; CDI: Clostridium difficile infection; ICU: Intensive care unit.

Table 3 Comparative average wholesale price for antibiotics used in the treatment of Clostridium difficile infection

Antibiotic	Cost per dose1	Usual regimen	Cost per treatment1
Metronidazole	$0.73
Vancomycin capsules (Vancocin HCL pulvules)	$31.83	125 mg 4 times/d × 10 d	$1273.20
Vancomycin intravenous formulation (generic)	$5.00/g ($0.62 per 125 mg dose)	125 mg 4 times/d × 10 d	$25.00
Fidaxomicin (Dificid)	$168.00	200 mg 2 times/d × 10 d	$3360.00
Rifaximin (Xifaxan)	$19.02 400 mg	400 mg 3 times/d × 20 d2	$1141.20

¹Average Wholesale Price (AWP); Anon, edition. Red Book online.

²Dose as a “chaser” after a course of oral vancomycin for recurrent CDI[151]. Via Drugdex System (internet database) Greenwood Village, CO: Thompson Healthcare, 2011[86]. CDI: Clostridium difficile infection.