Sandbox cdi

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2], Rim Halaby, M.D. [3]

Synonyms and keywords: CDI

Overview

Clostridium difficile infection (CDI) is defined as the acute onset of diarrhea (≥ 3 unformed stools in ≤24 hours) with either documented toxigenic Clostridium difficile (C. difficile) or its toxin, or colonoscopic or histopathological findings of pseudomembranous colitis in the absence of any other documented cause of diarrhea.

Classification

• Health-care facility onset health-care facility associated (HO-HCFA): Onset of symptoms within 3 days of admission to a health-care facility.
• Community onset health-care facility associated (CO-HCFA): Onset of symptoms within 4 weeks of discharge from a health-care facility.
• Community onset (CA): Onset of symptoms outside health-care facility or <3 days after admission to a health-care facility and has not been discharged from health-care facility in the previous 12 weeks.
• Indeterminate or unknown: Onset of symptoms after being discharged from a health-care facility 4-12 weeks previously.

Causes

Life Threatening Causes

Clostridium difficile infection can be a life-threatening condition and must be treated as such irrespective of the underlying cause.

Common Causes

• Cephalosporins
• Clindamycin
• Doxycycline
• Fluoroquinolones
• Histamine 2 receptor antagonists
• Penicillins
• Proton-pump inhibitors (PPIs)
• Rifapentin

Management

Characterize the symptoms: ❑ Diarrhea (onset, duration, pattern, bloody, mucous or watery) ❑ Mental status change ❑ Fever ❑ Abdominal pain ❑ Abdominal distention ❑ Nausea ❑ Vomiting ❑ Loss of appetite

Assess volume status: ❑ General condition ❑ Thirst ❑ Pulse ❑ Blood pressure ❑ Eyes ❑ Mucosa Examine the patient: ❑ Extremities (edema) ❑ Abdomen distension or tenderness ❑ Anorectal bleeding

Order tests: ❑ CBC ❑ ESR ❑ Serum electrolytes ❑ Total serum protein and albumin ❑ Stool analysis ❑ Urinalysis ❑ BUN ❑ Creatinine ❑ Serum glucose

Test the liquid stool for C. difficile: ❑ Nucleic acid amplification tests (NAAT) for C. difficile toxin genes such as PCR, OR ❑ Two or three steps glutamate dehydrogenase (GDH) screening with subsequent toxin A and B enzyme immunoassay

❑ Discontinue any inciting antibiotics ❑ Stop anti-motility drugs ❑ Take infection control precautions: ♦ Place the patient in a private room or in a room with another patient when CDI is suspected or confirmed ♦ Use hand hygiene and barrier precautions ♦ Use single use disposable equipment ♦ Disinfect environmental surfaces ❑ Assess the severity of the patient's condition to tailor the management

Mild or moderate initial episode ❑ Diarrhea ❑ Absence of peritoneal signs and symptoms

Severe initial episode ❑ Serum albumin <3g/dl Plus any ONE of the following: ❑ WBC ≥15,000 cells/mm3 ❑ Abdominal tenderness

Complicated severe initial episode ❑ Admission to the intensive care unit for CDI ❑ Hypotension with or without required use of vasopressors ❑ Fever ≥38.5 °C ❑ Ileus or significant abdominal distention ❑ Mental status changes ❑ Serum lactate levels >2.2 mmol/l ❑ WBC ≥35,000 cells/mm3 or <2,000 cells/mm3 ❑ End organ failure (mechanical ventilation, renal failure, etc.)

❑ Deliver supportive care ♦ IV fluid resuscitation ♦ Electrolyte replacement ♦ VTE prophylaxis ❑ Order a CT scan ❑ Obtain a surgical consult

❑ Administer antibiotics: ♦ Metronidazole 500 mg 3 times/day, orally, for 10 days, OR ♦ Vancomycin 125 mg 4 times/day in the case of allergy to metronidazole, pregnancy or breastfeeding

❑ Administer antibiotics: Vancomycin 125 mg 4 times/day for 10 days

Absence of abdominal distention: ❑ Administer antibiotics: ♦ Vancomycin 125 mg 4 times/day, orally or by NG tube, PLUS ♦ Metronidazole 500 mg 3 times/day ❑ Continue oral or enteral feeding

Presence of significant abdominal distention: ❑ Administer antibiotics: ♦ Vancomycin 500 mg 4 times/day, orally or by NG tube, PLUS ♦ Vancomycin 500 mg in a volume of 500 mL, per rectum, 4 times/day, PLUS ♦ IV Metronidazole 500 mg 3 times/day

In case of failure to respond within 5-7 days: ❑ Switch to Vancomycin 125 mg 4 times/day

First recurrence? ❑ Repeat the treatment of the initial episode ❑ Use vancomycin if severe

Second recurrence? ❑ Administer vancomycin in a tapered and/or pulsed way

Third recurrence? ❑ Consider fecal microbiota transplant (FMT)

The algorithm is based on the 2013 American Journal of Gastroenterology guidelines.

Do's

• Only unformed stools from patients with diarrhea should be tested for C. difficile. Inform the laboratory when a patient with ileus and complicated disease has a formed stool.

• Rectal swabs can be used for PCR and thus may be useful in timely diagnosis of patients with ileus.

• Begin empiric therapy for C. difficile regardless of the laboratory results among patients with high suspicion for CDI.

• Add vancomycin therapy delivered via enema to treatments in patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman’s pouch, ileostomy, or colon diversion.

• Test for C. difficile among patients with diarrhea in the context of immunosuppression, such as malignancy, chemotherapy, corticosteroid therapy, organ transplantation, and cirrhosis.

• Test for C. difficile among pregnant or periparturient women with diarrhea because of the increased rate of maternal and fetal mortality.

Management of CDI in IBD Patients

• Test for C. difficile among all patients with IBD who develop diarrhea following recent hospitalization or antibiotic use or in the setting of previously quiescent disease or with a disease flare.
• Test for C. difficile among all patients with an IBD flare.
• Consider the simultaneous treatment for IBD flare and empiric therapy against CDI among IBD patients who have severe colitis.

Don't s

• Don't screen for C. difficle among patients without diarrhea.
• Don't repeat testing for negative tests.
• Don't use anti-peristaltic agents to control diarrhea for confirmed or suspected CDI patients, as they may obscure symptoms and precipitate complicated disease.
• Repeat testing should be discouraged as it increases the likelihood of false positives and if requested, the physician should confer with the laboratory to explain the clinical rationale.
• Empiric therapy for CDI should not be discontinued or withheld in patients with a high pre-test suspicion for CDI.
• Dont treat asymptomatic C.Difficle carriers as treating such patients may increase the shedding of spores and growth of new resistant strains.
• Don't test for cure following an episode of clostridium difficile diarrhea.
• The evidence for the use of probiotics, Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus to decrease the incidence of antibiotic-associated diarrhea is insufficient.