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Clostridium Difficile Infection

Clostridium difficile is a gram-positive anaerobic bacterium most often associated with antibiotic-associated diarrhea. Symptoms may range from asymptomatic carrier states to severe pseudomembranous colitis and are caused by exotoxins produced by the organism: toxin A (an enterotoxin) and toxin B (a cytotoxin).

C. difficile spores are found frequently in hospitals, nursing homes, extended care facilities, and nurseries for newborn infants. They can be found on bedpans, furniture, toilet seats, linens, telephones, stethoscopes, fingernails, rings, floors, infants' rooms, and diaper pails. They even can be carried by pets. Thus, these environments are a ready source for infection with C. difficile.

Causes

Although Clostridium difficile infection can be caused by almost any antibiotic that disrupts the intestinal flora, it's classically associated with clindamycin use. Patients at high risk for this disorder include those taking many kinds of antibiotics or antineoplastic agents that have antibiotic activity; candidates for abdominal surgery; immunocompromised individuals; pediatric patients (infections are common in day-care centers); and those in nursing homes.

Additional factors that alter normal intestinal flora include enemas and intestinal stimulants. Clostridium difficile may be transmitted directly from patient to patient via contaminated hands of facility personnel (most common) or indirectly through contaminated equipment - such as bedpans, urinals, call bells, rectal thermometers, and nasogastric tubes - and surfaces - such as bed rails, floors, and toilet seats.

CLINICAL TIP Because spores of difficile are resistant to most commonly used facility disinfectants,the patient's room may be contaminated even after the patient is discharged. The immediate environment must be thoroughly cleaned and disinfected with 0.5% sodium hypochlorite.

Signs and symptoms

Symptoms include:

• watery diarrhea (at least three bowel movements per day for two or more days)
• fever
• loss of appetite
• nausea
• abdominal pain/tenderness

Diagnosis

Clostridium difficile infection is confirmed by identification of toxins, using one of the following methods:

• cell cytotoxin test - highly sensitive and specific for toxins A and B of C. difficile; results available in 2 days
• enzyme immunoassays-slightly less sensitive than the cell cytotoxin test, but results are obtained in a few hours; specificity is excellent.
• stool culture-most sensitive, with 2-day turnaround. Non-toxin-producing strains of C. difficile can be easily identified using three separate stool samples to test for the presence of the toxin.
• endoscopy (flexible sigmoidoscopy)­ may be used in patients who present with an acute abdomen but no diarrhea, making it difficult to obtain a stool sample. If pseudomembranes are seen, treatment for C. difficile is usually initiated.

Treatment

Withdrawing the causative antibiotic (if possible) resolves symptoms in patients who are mildly symptomatic. This is usually the only treatment required.For more severe cases, metronidazole 250 mg by mouth (P.O.) four times daily or 500 mg P.O. three times daily, or vancomycin 125 mg P.O. four times daily for 10 days are effective therapies, with metronidazole being the preferred treatment. Retesting for C. difficile is unnecessary if symptoms resolve.

In 10% to 20% of patients, C. difficile may recur within 14 to 30 days of treatment. Beyond 30 days, it's questionable whether the recurrence is a relapse or reinfection with C. difficile. If metronidazole was the initial treatment, low-dose vancomycin, given 125 mg P.O. four times daily for 21 days, may be effective. Alternatively, give vancomycin (125 mg P.O. four times daily) in combination with rifampin (600 mg P.O. twice daily) for 10 days.

There is no evidence to support the use of yogurt or Lactobacillus in these infections. Other experimental treatments include giving the yeast Saccharomyces boulardii with metronidazole or vancomycin and giving biological vaccines to restore normal intestinal flora.