Binary Toxin and Death after C. difficile Infection | CDC EID

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Volume 17, Number 6–June 2011
Research
Binary Toxin and Death after Clostridium difficile Infection
Sabrina Bacci, Kåre Mølbak, Marianne K. Kjeldsen, and Katharina E.P. Olsen
Author affiliations: European Programme for Intervention Epidemiology Training, Stockholm, Sweden (S. Bacci); and Statens Serum Institut, Copenhagen, Denmark (S. Bacci, K. Mølbak, M.K. Kjeldsen, K.E.P. Olsen)

Suggested citation for this article

Abstract
We compared 30-day case-fatality rates for patients infected with Clostridium difficile possessing genes for toxins A and B without binary toxin (n = 212) with rates for patients infected with C. difficile possessing genes for A, B, and binary toxin. The latter group comprised patients infected with strains of PCR ribotype 027 (CD027, n = 193) or non-027 (CD non-027, n = 72). Patients with binary toxin had higher case-fatality rates than patients without binary toxin, in univariate analysis (relative risk [RR] 1.8, 95% confidence interval [CI] 1.2–2.7) and multivariate analysis after adjustment for age, sex, and geographic region (RR 1.6, 95% CI 1.0–2.4). Similar case-fatality rates (27.8%, 28.0%) were observed for patients infected with CD027 or CD non-027. Binary toxin either is a marker for more virulent C. difficile strains or contributes directly to strain virulence. Efforts to control C. difficile infection should target all virulent strains irrespective of PCR ribotype.

Clostridium difficile infection (CDI) is a common cause of health care–associated diarrhea in industrialized countries (1), and the leading cause of intestinal infection related to antimicrobial drug consumption (2). Clinical manifestations range from mild to severe diarrhea, pseudomembranous colitis, toxic megacolon, sepsis, and ultimately death. Risk factors for CDI include duration of hospital stay, underlying illness, age (3), and previous use of virtually any antimicrobial drug, most frequently cephalosporins and fluoroquinolones (4–10).

The hypervirulent fluoroquinolone-resistant C. difficile PCR ribotype 027 North American pulsed-field type 1 (NAP1) (REA type BI, toxinotype III) has received attention as the cause of increasingly severe outbreaks and higher death rates, longer hospital stays, and frequent relapses (8,9,11,12). However, whether it really causes increased severity is questionable. Characteristics observed by previous studies may be due to selection bias or to the procedures used for diagnostic testing and reporting of cases; disease severity was similar in 2 groups of patients (PCR ribotype 027 and non-027) when recruitment to the study was done without reference to clinical signs and symptoms or PCR ribotype (13).

The pathogenicity of C. difficile is based on the action of at least 1 of the 2 main cytotoxins (A and B) acting as glycosyltransferases that modify guanose triphosphatases within the intestinal epithelial cells and lead to the disruption of the actin cytoskeleton. A recent study, which used a gene knock-out system, reinforced the fact that toxins A and B are comparable in terms of virulence, as shown by in vitro cytotoxicity and virulence in vivo (14). A binary toxin C. difficile transferase is found in some strains and belongs to the actin-modifying adenide dinucleotide protein–ribosyltransferases, which also impair the structure of actin cytoskeleton in epithelial cells (15,16). The pathologic significance of binary toxin is not yet clear. However, a recent study reports that binary toxin not only affects the actin cytoskeleton but also induces the formation of microtubule-based protrusions on the surface of epithelial cells, leading to increased adherence of bacteria (17).

Cultures positive for C. difficile are notifiable by the diagnostic laboratories in Denmark as part of the surveillance for gastrointestinal infections; in addition, isolates are selected under certain criteria and submitted to the National Reference Laboratory at Statens Serum Institut for further typing. The aim of the present study was to determine the case-fatality rate after diagnosis with C. difficile, according to toxin profile and PCR ribotype.

full-text:
Binary Toxin and Death after C. difficile Infection | CDC EID


Suggested Citation for this Article
Bacci S, Mølbak K, Kjeldsen MK, Olsen KEP. Binary toxin and death after Clostridium difficile infection. Emerg Infect Dis [serial on the Internet]. 2011 Jun [date cited].
http://www.cdc.gov/EID/content/17/6/976.htm

DOI: 10.3201/eid1706.101483


Comments to the Authors
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Sabrina Bacci, Department of Epidemiology, Statens Serum Institut, Artillerivej 5, Copenhagen S, 2300, Denmark; email: cci@ssi.dk