Office of Communicable Diseases

Center for Epidemiology
Advisory

Date: 2.28.07
To: All Rhode Island licensed physicians
Re: Virulent Clostridium difficile (NAP1 or ribotype 027): An emerging pathogen.

C difficile is an anaerobic spore forming bacillus that can cause diarrhea and pseudomembranous colitis. Complications include intestinal perforation and toxic mega-colon. The major risk factor is antibiotic exposure in a hospital or nursing home environment. C. difficile is not usually part of normal bowel flora and infection is acquired from fomites and environmental contamination with spores from a case. It can also be transmitted between patients by the hands of health care workers.

We are sending this advisory due to the emergence of a new strain of C. difficile -associated disease causing hospital outbreaks in several states (including CT, NY and MA), which has been reported by the Centers for Disease Control and Prevention (CDC) at scientific meetings. Over the past 3-4 years, several states have reported increased rates of C. difficile- associated disease, noting more severe disease (with complications such as perforation, shock, and increased rates of colectomy) and an associated increase in mortality. The new epidemic strain (PFGE type BI/NAP1, also called ribotype 027) appears to be more virulent, with the ability to produce greater quantities of toxins A and B.

In addition, it is resistant to newer fluoroquinolones. Increased fluoroquinolone resistance does not affect the management of infections caused by this strain, as fluoroquinolones have never been recommended for treatment of C. difficile -associated disease. However, resistance to fluoroquinolones may provide the new strain with an advantage to spread within healthcare facilities where these antibiotics are commonly used.

C. difficile is difficult to culture and none of the commercially available toxin tests differentiate between the various strains of C. difficile. The Department of Health (HEALTH) has noted anecdotal reports of severe C. difficile disease in Rhode Island hospitals. Though not yet culture confirmed, it is a reasonable assumption that the virulent strain is circulating in Rhode Island. HEALTH would like to emphasize that clinicians maintain a high index of suspicion for early recognition of possible cases, seek specialty consultation as needed (i.e. infectious disease consultation), and enforce strict adherence to infection control measures to prevent further transmission between patients.

The usual treatment for C. difficile -associated disease includes, if possible, stopping antibiotics being given for other purposes and/or treatment with metronidazole or oral vancomycin for GI-associated illness. In order to reduce selective pressure for vancomycin resistance in enterococci, current guidelines recommend the first-line use of metronidazole over vancomycin. While recent reports suggest that the new strain may not respond as well to treatment with metronidazole, metronidazole remains the appropriate first-line therapy for most cases. However, oral vancomycin should be used for patients:

• admitted to the ICU due to their C. difficile infection,
• with leukocytosis >15-20,000 cells/cubic mm,
• with new renal insufficiency with creatinine >2mg/dL,
• with elevated lactate levels,
• of advanced age ≥ 75 years.

For some patients with severe disease, colectomy may be life-saving. Recent literature from outbreaks of severe disease in Canada and the U.S. suggest that mortality is associated with advanced age (≥ 75 years), immunosuppression, shock requiring vasopressors, very high WBC (> 50,000 cells/mm), and elevated lactate levels ( ≥ 5 mmol/L).

Treatment of severe or recurrent C. difficile -associated diarrhea is an evolving science. Some important treatment considerations:

• Anti-motility agents should not be used in patients who have C. difficile diarrhea .
• Binding agents, such as cholestyramine, also bind oral vancomycin.
• "Tapering" and "pulsed" regimens of vancomycin may be effective for recurrent C. difficile- associated diarrhea.
• Adjunctive therapy (lactobacillus, Saccharomyces) for recurrent disease has limited data to support its use. Oral vancomycin kills lactobacillus.

We are asking healthcare facilities to monitor the number of C. difficile -associated disease cases. If an increase in rates or severity is observed, healthcare facilities should reassess compliance with the recommended infection control measures for known cases of C. difficile -associated disease including the following:

• Hand hygiene using soap and water or an alcohol-based hand gel. If your institution experiences a documented outbreak, consider using only soap and water for hand hygiene when caring for patients with C. difficile -associated disease after gloves are removed; there is a theoretical possibility that alcohol-based hand rubs may not be as effective against spore-forming bacteria.
• Contact precautions.
• Environmental cleaning and disinfection strategies.

Report institutional outbreaks to the Office of Communicable Disease at 222-2577.

For more information and publications see: http://www.cdc.gov/ncidod/dhqp/id_Cdiff.html

Suggested reading (first publication available at above link):

1. Sunenshine RH, McDonald LC. Clostridium difficile -associated disease: New challenges from an established pathogen. Cleveland Clinic J Med. Feb 2006; 73:187.

2. Bartlett JG. Narrative review: the new epidemic of Clostridium difficile -associated enteric disease. Ann Intern Med 2006 Nov 21;145(10):758-64.

Acknowledgement: RI-Infectious Disease physicians and infection control practitioners provided review and comment.