Laboratory technical advances in the diagnosis of clostridium difficile

Abstract

Clostridium difficile (C. difficile) is a spore-forming, anaerobic, gram positive rod that colonizes the colon of 5 % of healthy adults and 30-70 % of healthy infants [1]. The organism can also be found in a variety of environmental sources including soil, river water, domestic animals, and home and healthcare environments [2]. C. difficile acquired its name from the observations by Hall and O'Toole [3] in the difficulty of isolating the organism because of its slow growth (doubling time 40-70 min) compared to other Clostridium spp. During logarithmic growth, when vegetative cells predominate, the organism is very aerointolerant. In 1978, prior knowledge of the organism and the observation that antibiotic associated diarrhea was associated with a cytotoxin in the hamster model, converged in the work by Bartlett et al. that demonstrated that C. difficile caused disease in humans through the elaboration of a cytotoxin [2, 4, 5]. Later it was established that the organism produces two toxins, toxin A, a 308 kDa enterotoxin and toxin B, a 270 kDa cytotoxin. Both toxins cause disease by glycosylating small GTPases such as Rho, Rac, and Cdc42 in the cell [2, 6]. Glycosylation of these small proteins disrupts signaling pathways causing irreversible changes in cellular morphology and consequent inhibition of cell division and membrane trafficking, leading to cell death [2, 6].