Clostridium difficile infection resident survival guide

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

Definition

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.

• 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

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Clostridium difficile infection itself may present or complicate as a life-threatening condition and must be treated as such irrespective of the causes.

Common Causes

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

Management

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

Examine the patient: 1. Assess volume status: ❑ General condition ❑ Thirst ❑ Pulse ❑ Blood pressure ❑ Eyes ❑ Mucosa 2. General examination: ❑ Extremities (Edema) ❑ Abdomen (Distension or tenderness) ❑ Anorectal (Bleeding) ❑ CVS ❑ RS

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

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

❑ Discontinue any inciting antibiotics ❑ Assess the severity of the patient's condition to tailor the management

Diarrhea plus any additional signs or symptoms not meeting severe or complicated criteria

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

❑ 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.)

Mild or moderate initial episode

Severe initial episode

Complicated severe initial episode

Deliver supportive care

Administer antibiotics: ❑ Metronidazole 500 mg 3 times/day, orally, for 10 days

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 ❑ IV Metronidazole 500 mg 3 times/day ❑ Consider administering rectal vancomycin in case of complete ileus ❑ 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 ❑ Consider administering rectal vancomycin in case of complete ileus

First recurrence? ❑ Repeat the treatment of the initial episode

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

Yes

No

❑ Isolate the patient ❑ Discontinue non-C.Difficle treatment antibiotics ❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Appropriate attention to infection prevention and control ❑ Emperical antibiotic (Metronidazole OR vancomycin based on clinical severity) ❑ Hand hygiene and barrier precautions ❑ Single-use disposable equipment should be used

❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Review further inciting antibiotic and other drug history and risk factors for CDI

Hospital approval/affordable for Nucleic acid amplification tests (NAATs) for C. difficile toxin

Yes

No

Fecal glutamate dehydrogenase (GDH) screening tests for C. difficile

Positive

Negative

Enzyme immunoassay (EIA) for toxins A + B

Evalute for other acute diarrhea causes

Negative

Positive

Fecal nucleic acid amplification tests: ❑ Polymerase chain reaction (PCR): Most preferred ❑ Isothermal amplification tests

Negative

Positive

Evalute for other acute diarrhea causes

No strong clinical suspicion of CDI

Strong clinical suspicion of CDI

Rx for CDI

❑ Isolate the patient ❑ Discontinue non-C.Difficle treatment antibiotics ❑ Stop all anti-peristaltic agents ❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Appropriate attention to infection prevention and control ❑ Hand hygiene and barrier precautions ❑ Single-use disposable equipment should be used

Assessment of severity

Any of the following: ❑ Admission to intensive care unit for CDI ❑ Hypotension with or without required use of vasopressors ❑ Fever ≥20.5 °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.)

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

Diarrhea plus any additional signs or symptoms not meeting severe or complicated criteria

Severe and complicated

Severe

Mild-moderate

Significant abdominal distention

No significant abdominal distention

Oral vancomycin 125 mg QID X 10 days

Oral metronidazole 500 mg TID X 10 days

❑ Oral vancomycin 125 mg QID Plus ❑ Intravenous metronidazole 500 mg TID ❑ CT ❑ Venous thromboembolism (VTE) prophylaxis

Any ONE of the following: ❑ Failure to respond to metronidazole therapy within 5–7 days ❑ Intolerant/allergic to metronidazole ❑ Pregnant/breastfeeding women

❑ Oral vancomycin 500 mg QID Plus ❑ Vancomycin per rectum (500 mg in a volume of 500 ml QID) Plus ❑ Intravenous metronidazole 500 mg TID ❑ Venous thromboembolism (VTE) prophylaxis

CT showing colon wall thickening, ascites, “megacolon”, ileus, or perforation

CT normal

❑ Oral vancomycin 125 mg QID X 10 days OR ❑ Oral fidaxomicin 200 mg BD X 10 days)

Surgical consultation and operative management in required cases

❑Monitor patient status ❑Complete the antibiotic course ❑ Discharge when completely recovered ❑Disinfection of environmental surfaces using an Environmental Protective Agency (EPA)-registered disinfectant

First recurrence ❑ Confirm diagnosis as above

Severe

Mild-moderate

Initial vancomycin regimen

Intial metronidazole regimen

❑Tapered and pulsed vancomycin regimen Oral vancomycin 125 mg QID, followed by 125 mg daily pulsed every 3 days for ten doses X 10 days

❑Tapered and pulsed vancomycin regimen Oral vancomycin 125 mg QID, followed by 125 mg daily pulsed every 3 days for ten doses X 10 days

❑ Oral metronidazole 500 mg TID X 10 days OR ❑ Oral vancomycin 125 mg QID X 10 days

Second recurrence ❑ Confirm diagnosis as above ❑ Pulsed vancomycin regimen

Third recurrence ❑ Confirm diagnosis as above ❑ Pulsed vancomycin regimen ❑ Fecal microbiota transplant trail

Do's

• Only stools from patients with diarrhea should be tested for C. difficile.. Very occasionally, a patient with ileus and complicated disease will have a formed stool, in which case the laboratory should be made aware of this special clinical situation. Rectal swabs can be used for PCR and thus may be useful in timely diagnosis of patients with ileus.
• Vancomycin therapy delivered via enema should be added 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.
• Do C. difficile testing in all patients with IBD who develop diarrhea in the setting of previously quiescent disease or with a disease flare. Initiate empirical therapy directed against CDI in inflammatory bowel disease IBD patients with severe colitis.
• Do C. difficile testing in patients with underlying immunosuppression (including malignancy, chemotherapy, corticosteroid therapy, organ transplantation, and cirrhosis), with any diarrheal illness.
• Do C. difficile testing in women who are pregnant or periparturient with any diarrheal illness because of increased rate of maternal and fetal mortality.
• Until the resolution of diarrhea, a patient with CDI should be placed in a private room or in a room with another patient with documented CDI as C.Difficle can be cultured from the skin surface of patients and from the surfaces in rooms of infected patients. The ideal recommendation is to maintain contact precautions for 48hr after diarrhea ceases.
• The evidence for the use of probiotics, Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus to decrease the incidence of antibiotic-associated diarrhea is insufficient.

Don't s

• Don't screen for clostridium difficle among patients without diarrhea.
• Don't repeat testing for negative tests.
• Dont 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.

References

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