Identification of Toxemia in Patients with Clostridium difficile Infection

Toxemia can develop in Clostridium difficile -infected animals, and correlates with severe and fulminant disease outcomes. Circumstantial evidence suggests that toxemia may occur in patients with C . difficile infection (CDI), but positive diagnosis is extremely rare. We analyzed the potential for C . difficile toxemia in patients, determined its characteristics, and assessed challenges. C . difficile toxins in serum from patients were tested using an ultrasensitive cell-based assay and further confirmed by Rac1 glucosylation assay. The factors that hinder a diagnosis of toxemia were assessed, including investigation of toxin stability, the level of toxins-specific neutralizing antibodies in sera and its effect on diagnosis limits. CDI patients develop detectable toxemia in some cases (2.3%). Toxins were relatively stable in stored sera. Neutralizing anti-toxin antibodies were present during infection and positively correlated with the diagnosis limits. Thus, the masking effect of toxin-specific neutralizing antibodies is the major obstacle in diagnosing C . difficile toxemia using cell-based bioassays.