Clostridium difficile: Recent Epidemiologic Findings and Advances in Therapy

Abstract

Clostridium difficile-associated disease (CDAD) has become an important public health problem. The causative organism is acquired by the oral route from an environmental source or by contact with an infected person or a health care worker who serves as a vector. Disruption of the bowel microflora, generally by antibiotics, creates an environment that allows C. difficile to proliferate. Organisms produce toxins A and B, which cause intense inflammation of the colonic mucosa. The syndrome that results includes severe diarrhea, fever, abdominal pain, and leukocytosis. A new 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. Clostridium difficile NAP-1 characteristically generates large amounts of toxins A and B, as well as an additional binary toxin and is associated with enhanced morbidity and a poor response to antibiotic therapy. Mild cases of CDAD may respond to cessation of antibiotic therapy, perhaps related to antibody production by the infected person, but most infected persons require antimicrobial therapy. Vancomycin has been approved by the United States Food and Drug Administration for treatment of CDAD, but reluctance to use this antibiotic in the hospital setting has led to reliance on metronidazole as first-line therapy. Recent studies show a high rate of failure, due either to infection by NAP-1 or to the presence, in hospitals, of older and sicker adults who have been treated with many broad-spectrum antibiotics. Nitazoxanide, bacitracin, teicoplanin, and fusidic acid are additional agents that have published efficacy for this indication in humans. Rifaximin and PAR-101 are under investigation. Other therapies, including polymers that bind C. difficile toxin and monoclonal antibodies to toxins, and preventive measures such as toxoid vaccines are also under study.

Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?

“…[1][2][3][4][5] In addition to these primary factors, a number of additional co-factors are known to increase the risk of CDAD in an individual patient and include advanced age, medical comorbidities, long hospital stays, suppression of gastric acid production by H2 blockers and proton pump inhibitors, enteral intubation or feeding, and the number, type and duration of antibiotic exposure. [1][2][3][4][5][8][9][10][11] Specific antibiotic exposure risk varies somewhat between studies, but the antibiotics most commonly showing an increased risk for CDAD include clindamycin, extended spectrum cephalosporins and quinolones. [1][2][3][4][5][8][9][10][11] Antibiotics believed to have a decreased risk of CDAD include vancomycin, tetracyclines, macrolides and aminoglycosides.…”

“…[1][2][3][4][5][8][9][10][11] Specific antibiotic exposure risk varies somewhat between studies, but the antibiotics most commonly showing an increased risk for CDAD include clindamycin, extended spectrum cephalosporins and quinolones. [1][2][3][4][5][8][9][10][11] Antibiotics believed to have a decreased risk of CDAD include vancomycin, tetracyclines, macrolides and aminoglycosides. HSCT recipients in particular are known to be subjected to a variety of risk factors for CDAD, such as prolonged hospital stays, longterm and broad-spectrum antibiotic use, altered integrity of the intestinal mucosa from chemoradiation therapy and GVHD.…”

“…[1][2][3][4][5] The re-emergence of CDAD has been associated, in part, with the detection of a new hypervirulent strain of C. difficile known as the North American pulsed-field gel electrophoresis type 1 (NAP-1) strain. [6][7][8][9][10][11] In addition, there is growing concern regarding the selection of the optimal therapy for severe CDAD as well as the significant rate of recurrent disease after initially successful treatment regimens. [1][2][3][4][5] Hematologic stem cell transplant (HSCT) recipients have a large number of well-recognized risk factors for the development of CDAD.…”

Pseudo-outbreak of Clostridium difficile associated diarrhea (CDAD) in a tertiary-care hospital

“…Clostridium difficile is the most frequent cause of hospital-acquired diarrhea 18,20 . More recently C. difficile associated disease has become more severe leading to more frequent complications such as toxic megacolon and is more refractory to treatment 14 .…”

“…More recently C. difficile associated disease has become more severe leading to more frequent complications such as toxic megacolon and is more refractory to treatment 14 . Since the early 2000s, a new hyper virulent strain, NAP1/BI/027, has been responsible for outbreaks in North America and Europe 20,27,31 . Its epidemiology in Brazil is unknown and there have been no reports of outbreaks with hyper virulent strains in this country 3,30 .…”