Clostridium difficile associated infection, diarrhea and colitis

Table 1 Populations at increased risk for C. difficile

Patients who take the following drugs

Antibiotics

Proton pump inhibitors

Valacyclovir

Patient characteristics

IBD

Serous underlying illness-comorbidities

Gastrointestinal surgery/manipulations

Advanced age

Immune-compromising conditions (post transplantation)

Peri-partum

Environment

Prolonged stay in health-care settings

Laboratory factors

Hypoalbuminemia

Low levels of anti-toxin and B antibodies

Table 2 Laboratory diagnosis of C. difficile

Test	Sensitivity (%)	Specificity (%)	PPV	NPV
Enzyme immunoassay	73	98	73	98
Real-time PCR	93	97	76	99
Cell culture assay	77	97	70	98
Anaerobic culture for toxigenic C. difficile strains	100	96	68	100

Peterson LR, Manson RU, Paule SM, Hacek DM, Robicsek A, Thomson RB Jr, Kaul KL. Detection of toxigenic Clostridium difficile in stool samples by real-time polymerase chain reaction for the diagnosis of C. difficile-associated diarrhea. Clin Infect Dis 2007; 45(9): 1152-1160.

Table 3 Diagnosis of C. difficile

Enzyme immunoassay for toxins A & B - 80% sensitive

Use 3 samples

Cytotoxicity assay-more sensitive and specific, but takes 24-48 h

Table 4 CDAD severe disease

Patient characteristics

Older patients (> 65 yr)

Presence of comorbid conditions

Immune compromising conditions

Systemic immune response syndrome

Organ failure

Renal

Respiratory

Hypotension

Laboratory markers

Marked leukocytosis > 15 000

Renal failure Cr > 2.3 mg/L

Hypoalbuminemia

Extent of disease

Pancolitis by imaging modalities

Complications

Ileus

Toxic megacolon

Intestinal perforation

Any one of the above calls for classification as ‘severe disease’, using the authors’ approach

Table 5 Therapeutic approach to patients with severe C. difficile infection

Oral vancomycin, 500 mg q.i.d

Substitute intracolonic vancomycin infusion if ileus and add metronidazole 500 mg q.i.d., IV

Consider IV immunoglobulin therapy (400 mg/kg)

Surgical evaluation for acute abdomen

Table 6 Risk factors for relapse (occurs in 10%-25% of cases¹)

Prolonged antibiotic usage

Prolonged hospitalization

Age > 65 yr

Diverticulosis

Comorbid medical condition(s)

¹Increased risk of relapse with increased number of relapses. Kelly CP, Lamont JT. Up-to-date May 2008.

Table 7 Therapeutic approach to patients with recurrent C. difficile infection

Second course of initial antibiotic, if the patient has mild/moderate disease; if severe disease, begin vancomycin

If recurrence after vancomycin, re-evaluate and treat with oral vancomycin and add tapering vancomycin regime and s. boulardii

If recurrence despite above, consider

Rifampicin

Cholestyramine

Fecal bacteriotherapy

Table 8 Indications for emergency colectomy

Based upon

30-d mortality

Leukocytosis ≥ 20 × 109/L

Lactate ≥ 5 mmoL/L

Age ≥ 75 yr

Immunosuppression

Shock requiring vasopressors

Especially in the presence of:

Toxic megacolon

Multi-organ system failure

Kelly CP, Lamont JT. Up-to-date May 2008.

Table 9 Strength of recommendation and quality of evidence

Category/grade	Definition
Strength of recommendation
A	Good evidence to support a recommendation for use
B	Moderate evidence to support a recommendation for use
C	Poor evidence to support a recommendation
Quality of evidence
I	Evidence from ≥ 1 properly randomized, controlled trial
II	Evidence from ≥ 1 well-designed clinical trial, without randomization; from cohort or case-control analytic studies (preferably from > 1 center); from multiple time series; or from dramatic results from uncontrolled experiments
III	Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees

Adapted from Canadian Task Force on the Periodic Health Examination. Can Med Assoc J 1979; 121(9): 1193-1254.