Clostridium difficile-associated diarrhea: a review

Abstract

Clostridium difficile–associated diarrhea (CDAD) has become a major public health problem. The offending pathogen is acquired by the fecal-oral route from an environmental source or by contact with an infected person or health care worker who serves as a vector. Alteration of the intestinal microflora, frequently by antibiotics, generates a favorable environment results in the proliferation of C. difficile. The pathogen is not invasive but produces two toxins, A and B, that lead to severe inflammation of the colonic mucosa manifested as profound diarrhea, fever, abdominal pain, and leukocytosis. A new hypervirulent strain of C. difficile has become prevalent in the United States, Canada, and the United Kingdom. Identified by pulsed-field gel electrophoresis (PFGE), this strain is called North America PFGE type 1, abbreviated as NAP-1, and characteristically generates large amounts of toxins A and B, in addition to a binary toxin, and is associated with higher morbidity and failure of antibiotic therapy. Mild cases of CDAD may respond to withdrawal of antibiotic therapy, however the majority of patients require C. difficile-specific antimicrobial therapy. The US FDA has approved oral vancomycin for treatment of CDAD, but reluctance to use this antibiotic due to the fear of developing vancomycin- resistant organisms in the hospital setting has made metronidazole the recommended first-line therapy for mild to moderate disease. Some newer studies show a high rate of failure, due to infection by NAP-1 or to the presence, in hospitals, of geriatric patients with more concurrent illnesses who may also have been treated with many broad-spectrum antibiotics. The recurrence rate after initial successful treatment can be as high as 20-30%, depending on the initial treatment. A more C. difficile-targeted non-absorbable bacterial RNA polymerase inhibitor, fidaxomicin (also known as OPT-80 and PAR-101), has recently been approved in the US with initial efficacy similar to vancomycin and a lower recurrence rate. Some additional agents that have shown efficacy in humans are nitazoxanide, bacitracin, teicoplanin, and fusidic acid. Rifaximin, polymers that bind C. difficile toxin, monoclonal antibodies to toxins, and preventive measures such as toxoid vaccines are under investigation. Interventions for treatment of recurrences include repeated vancomycin or fidaxomicin courses, probiotics, rifaximin, intravenous immunoglobulin and fecal transplants. Measures for preventing the spread of the pathogen, appropriate diagnostic testing, and treatment may avert morbidity and mortality due to CDAD.