para>C. difficile is the most common cause of acute diarrheal illness in long-term care facilities. Elderly patients also commonly have multiple other risk factors (comorbid disease, antibiotic exposure, medication use).
Pediatric Considerations
Neonates have a higher rate of C. difficile colonization (25-80%) but are generally less symptomatic than adults (possibly due to immature toxin receptors)
Frequently serve as carrier for symptomatic infection in adults
GENERAL PREVENTION
- A comprehensive infection control program decreases the incidence of C. difficile infection.
- 2010 Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDS) guidelines:
- For health care workers, patients, and visitors:
- Contact precautions, including gloves and gowns, on entry to room
- Alcohol-based hand sanitizers not effective. Hand hygiene with soap and water before and after patient interaction
- Accommodate patients with C. difficile infection in private rooms, if possible.
- Environmental cleaning and disinfection
- Disinfection with hypochlorite solution or other spore-killing solutions
- Identification and reduction of environmental sources of C. difficile, including the use of nondisposable rectal thermometers
- Antimicrobial use restrictions
- Minimize the frequency and duration of antibiotic therapy.
COMMONLY ASSOCIATED CONDITIONS
Pseudomembranous colitis, toxic megacolon, sepsis, colonic perforation
DIAGNOSIS
HISTORY
- Age and underlying comorbidities
- Recent antibiotic use
- Diarrhea (defined as >3 stools in 24 hours) that is watery, foul-smelling, and sometimes bloody (1)
- Fever (<10%), anorexia, nausea
- Recent hospitalization or stay at nursing facility
PHYSICAL EXAM
Physical exam findings range from mild abdominal pain to peritoneal findings and shock:
- Mild or moderate disease: mild lower abdominal pain, often cramping pain
- Severe disease: fever, nausea/vomiting, dehydration
- Severe, complicated disease: shock, peritonitis, ileus
DIFFERENTIAL DIAGNOSIS
- Antibiotic-associated diarrhea
- Inflammatory bowel disease
- Enteric infections
- Food poisoning
DIAGNOSTIC TESTS & INTERPRETATION
- SHEA/IDSA guidelines (2)
- Mild or moderate disease: leukocytosis with white blood cell (WBC) count <15,000 cells/μL and a serum creatinine level <1.5 — the premorbid level
- Severe, uncomplicated disease: leukocytosis with WBC count >15,000 cells/μL or a serum creatinine level >1.5 — the premorbid level
- Severe, complicated disease: markers of severe infection include hypotension, sepsis, markedly elevated WBC count, and bandemia
- Other signs seen on imaging include obstruction, perforation, toxic megacolon, and colonic wall thickening
Initial Tests (lab, imaging)
- Polymerase chain reaction (PCR)-based testing is preferred for C. difficile. Rapid, highly sensitive, and hightly specific (2)[B].
- Alternative to PCR: screening and confirmatory testing. C. difficile common antigen tests: Tests for glutamate dehydrogenase (GDH), found in both toxic and nontoxic strains of C. difficile (sensitivity, 85-95%; specificity, 89-99%).
- Confirmatory: enzyme immunoassay for toxins (A/B or A); rapid results, inexpensive, easy to use (sensitivity 63-94%)
- Stool culture is the most sensitive test; however, non-toxin-producing strains also detected.
- Repeat testing during the same episode of diarrhea is not recommended. Stool carriage persists for 3 to 6 weeks after successful treatment (2)[A].
Diagnostic Procedures/Other
- Endoscopy can be used to evaluate for pseudomembranes and exclude other conditions
- While not all patients with C. difficile infection have pseudomembranes, their presence is pathognomonic for C. difficile.
- Flexible sigmoidoscopy may miss 15-20% of pseudomembranes present in the proximal colon.
- Colonoscopy evaluates the entire colon: used when diagnosis is in doubt or severity demands rapid diagnosis
- Plain films may show thumbprinting and colonic distension.
- CT may show mucosal wall thickening, thickened colonic wall, and pericolonic inflammation.
Test Interpretation
Pseudomembranes consist of inflammatory and cellular debris that forms visible exudates that can obscure the underlying mucosa. These exudates have a yellow to grayish color.
TREATMENT
GENERAL MEASURES
- Avoid antimotility agents and opiates.
- Avoid indiscriminate use of antibiotics.
- Proton pump inhibitors associated with recurrent infection, however have not shown to be causal
- Discontinue offending antibiotic, if possible.
MEDICATION
First Line
- Mild or moderate infection (3)[A]
- Oral metronidazole is the drug of choice for mild to moderate C. difficile infection:
- 500 mg PO TID for 10 to 14 days
- If patient is unable to take oral medications, then intravenous (IV) metronidazole or intraluminal vancomycin can be used.
- Severe infection (3)[A]
- Enteral vancomycin is 1st-line therapy in patients with severe or fulminant C. difficile infection:
- 125 mg PO QID for 10 to 14 days
- Vancomycin retention enema if unable to take PO, or if there is evidence of poor gastrointestinal motility
- Severe, complicated infection-consider surgical and critical care consultation (3)[A]
- Vancomycin: 500 mg PO QID and metronidazole 500 mg PO TID
- 1st recurrence
- Treat the same as 1st episode
- 2nd recurrence
- Vancomycin taper and/or pulse: vancomycin 125 mg PO QID for 10 to 14 days, then 125 mg PO BID for 7 days, then 125 mg PO once daily for 7 days, then 125 mg PO every 2 to 3 days for 2 to 8 weeks:
- Pulse dosing every 2 to 3 days allows spores to germinate and then be killed.
ALERT
When using vancomycin for treatment of C. difficile infection, oral or rectal formulations must be used. IV formulations are not excreted into the colonic lumen.
Second Line
- Vancomycin: indicated for patients who cannot tolerate or have failed metronidazole therapy and for those who are pregnant
- Fidaxomicin is another option 200 mg PO BID. Similar cure rates to vancomycin and lower recurrence rates, however can be cost prohibitive.
- Fidaxomicin rapidly kills C. difficile whereas vancomycin inhibits growth. Fidaxomicin has a narrow antimicrobial spectrum and helps preserve normal anaerobic flora.
- Fecal transplant: Stool from healthy, screened donor. Administered via either rectal or oral route. Highly effective treatment for recurrent infections (>90% cure rate) when offending antibiotic stopped. Recipient gut flora have been transformed in as few as 3 days following fecal transplantation (4)[A].
SURGERY/OTHER PROCEDURES
- Most patients improve with conservative management and oral antibiotics.
- Patients with severe fulminant colitis develop paralytic ileus, leading to distention (megacolon), and potential perforation.
- Severe lower quadrant abdominal pain or signs of hemodynamic instability in the setting of known infection should prompt surgical and critical care consultation.
ALERT
BI/NAP1/027 strain associated with fulminant colitis, often requiring surgical intervention. More common in younger patients with severe disease.
COMPLEMENTARY & ALTERNATIVE MEDICINE
- Adjunctive therapy with intravenous immunoglobulin (IVIG) has shown initial promise, but more data are required before routine clinical use.
- Probiotics have an (strain-specific) inhibitory effect on C. difficile and may play a role in prevention.
- Other investigational treatment options:
- New antibiotics (Rifalazil, Tolevamer, and Ramoplanin)
- Monoclonal antibodies to directly modulate the effects of toxins
- Vaccine form of C. difficile antitoxin antibody
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
- Hypovolemia
- Inability to keep up with enteric losses
- Hematochezia
- Electrolyte disturbances
IV Fluids
To maintain volume status
Discharge Criteria
- Decreased diarrhea severity and frequency
- Tolerating oral diet and medications
- Do not repeat testing for toxins, as they may shed for weeks following an acute infection.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Many patients can be treated as outpatients.
Patient Monitoring
- Relapses of colitis occur in 15-30%
- Relapses typically occur 2 to 10 days after discontinuing antibiotics.
DIET
Regular diet or NPO if severe and surgical evaluation required
PATIENT EDUCATION
Educate patients about C. difficile transmission, the importance of hand washing, and the appropriate use of antibiotics.
ALERT
Alcohol-based hand sanitizers are not effective against C. difficile. Wash with soap and water.
PROGNOSIS
- Most patients improve with conservative management and oral antibiotics.
- 1-3% of patients develop severe/fulminant colitis requiring emergency colectomy.
REFERENCES
11 Khanna S, Pardi DS. Clostridium difficile infection: management strategies for a difficult disease. Therap Adv Gastroenterol. 2014;7(2):72-86.22 Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372(16):1539-1548.33 Debast SB, Bauer MP,Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Clin Microbiol Infect. 2014;20(Suppl 2):1-26.44 Shankar V, Hamilton MJ, Khoruts A, et al. Species and genus level resolution analysis of gut microbiota in Clostridium difficile patients following fecal microbiota transplantation. Microbiome. 2014;2:13.
ADDITIONAL READING
- Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431-455.
- Kassam Z, Lee CH, Yuan Y, et al. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):500-508.
- McCollum DL, Rodriguez JM. Detection, treatment, and prevention of Clostridium difficile infection. Clin Gastroenterol Hepatol. 2012;10(6):581-592.
CODES
ICD10
- A04.7 Enterocolitis due to Clostridium difficile
ICD9
- 008.45 Intestinal infection due to Clostridium difficile
SNOMED
- 186431008 Clostridium difficile infection (disorder)
- 423590009 Clostridium difficile colitis (disorder)
- 5891000119102 Clostridium difficile diarrhea (disorder)
CLINICAL PEARLS
- C. difficile is spread by fecal-oral contact.
- Alcohol-based hand sanitizers are ineffective against C. difficile. Wash hands with soap and water.
- Testing and treatment of asymptomatic patients is not recommended.
- PCR is the preferred initial test.
- Patients may shed organism or toxin for weeks after treatment. Repeat toxin assays following treatment are not helpful.
- Metronidazole remains the drug of choice for mild to moderate disease.