Prevalence and pathogenicity of binary toxin–positive Clostridium difficile strains that do not produce toxins A and B

Abstract

Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B (TcdB). A third toxin, called binary toxin (CDT), can be detected in 17% to 23% of strains, but its role in human disease has not been clearly defined. We report six independent cases of patients with diarrhoea suspected of having C. difficile infection due to strains from toxinotype XI/PCR ribotype 033 or 033-like, an unusual toxinotype/PCR ribotype positive for CDT but negative for TcdA and TcdB. Four patients were considered truly infected by clinicians and were specifically treated with oral metronidazole. One of the cases was identified during a prevalence study of A−B−CDT+ strains. In this study, we screened a French collection of 220 nontoxigenic strains and found only one (0.5%) toxinotype XI/PCR ribotype 033 or 033-like strain. The description of such strains raises the question of the role of binary toxin as a virulence factor and could have implications for laboratory diagnostics that currently rarely include testing for binary toxin.

Clostridium difficile infection: Evolution, phylogeny and molecular epidemiology

“…CDT has been associated with more severe disease (Barbut et al, 2005), but not proven to cause disease on its own Gerding et al, 2014). While strains that produce CDT in the absence of toxins A and B have recently been linked to symptomatic CDI in immunocompromised individuals, their pathogenicity in general still remains unclear (Androga et al, 2015;Eckert et al, 2015;Grandesso et al, 2016).…”

An Update on Clostridium difficile Toxinotyping

“…As already mentioned above, type 244/IXb is an emerging cause of community infections in Australia (27). Toxinotype XI (all subtypes) is still rare in humans, and its role in the associated disease is debated because of the lack of toxins A and B and production of CDT only (34).…”

Clostridium difficile infection: Early history, diagnosis and molecular strain typing methods

“…A further study suggested that CDT was a predictor of recurrent infection, and its presence may require longer antibiotic treatments [148]. CDT þ C. difficile strains that do not produce toxins A and B have been described in independent cases of patients with diarrhoea suspected of having CDI [149].…”