Clostridium difficile Toxin A in Infants

C difficile produces two toxins, each of which is cytotoxic and lethal to animals [1]. Whether one or both of the toxins is responsible for pseudomembranous colitis in humans is unknown. C difficile is rarely found in the intestinal tracts of healthy adults, and then only in relatively low numbers. The same numbers of C difficile found in adults with pseudomembranous colitis may be present in infants with no obvious adverse effects [3]. The primary cytotoxin of C difficile, toxin B, may also be found in these infants, but the presence of toxin A, which causes intestinal fluid accumulation and mucosal necrosis in hamsters, has not been demonstrated [3]. However, an ELISA developed in our laboratory has been used to detect toxin A in fecal specimens from adults with pseudomembranous colitis [1]. Using this assay, we attempted to determine whether this toxin might be found in hospitalized infants with no obvious gastrointestinal distress. Ten of the 21 infants tested had toxin A in their feces. No infant had toxin A in the absence of toxin B. This is not surprising, because both toxins are produced in about the same ratio in vitro by all strains of C difficile we have tested [1]. In general, those specimens with high titers of toxin B had correspondingly high concentrations of toxin A. The infant with the highest titers of both toxin A and B was the eight-month-old infant with a clinical diagnosis of antibiotic-associated colitis. The other nine infants with toxin A had no enteric symptoms. Hence, the lack of diarrhea in infants colonized with C difficile cannot be explained by the absence from their stools of toxin A, which caused enterotoxin-like symptoms in animals [1]. Conversely, the finding of toxin A does not necessarily imply the existence of associated enteric signs. It may be that certain infants are protected from the effects of the toxin(s), because, for example, they lack toxin receptors or the means for further processing of the toxin.