Pathogenesis of postantibiotic diarrhoea caused by Clostridium difficile: an in vitro study in the rabbit intestine.

Abstract

SUMMARY To elucidate the pathophysiological changes leading to postantibiotic diarrhoea caused by Clostridium difficile and its cytotoxin, oral ampicillin was given to rabbits, and jejunal, ileal, and caecal segments of those that developed diarrhoea were investigated in vitro. The rabbits that, in response to treatment, harboured Clostridium difficile in their colonic lumen were studied, and the results expressed according to the presence or absence of Clostridium difficile and/or its cytotoxin.Thus, we refer to either CD+ or CD-segments. The influx of glucose, phenylalanine, glycylphenylalanine, and lysine across the brush border of jejunum and ileum of CD+ segments was severely impaired, while only slightly blunted in CD-. No significant change was detected in the influx of glutamic acid in the jejunum of all treated animals and in the CD-ilea. Morphologic damage in ileum and caecum of CD+ was also more evident than in CD-. Transepithelial ion transport across short circuited ileal mucosa (CD+ and CD-) revealed secretory changes in Cl net transport that were more marked in CD-. We conclude that: (1) Clostridium difficile may also colonise the upper intestinal tract, where it induces morphological and functional damage, severely impairing nutrient absorption; and (2) the ileum contributes to the diarrhoea caused by CD even when the micro-organism is confined to the more distal gut by showing moderate impairment of nutrient absorption and marked electrolyte secretion.The administration of antibiotics, particularly by the oral route, may be accompanied by gastrointestinal complaints, the most severe of which is diarrhoea. It is well known that Clostridium difficile (CD) may mediate such a complication by inducing a colitis of variable severity; the most widely recognised form being pseudomembranous colitis, an entity occurring both in adults and in children.' 2 Although it is well known that CD releases toxic factors (two of which have been extensively investigated -toxin A or enterotoxin and toxin B or cytotoxin),' the pathophysiological changes actually ensuing after CD

Enteroaggregative Escherichia coli heat-stable enterotoxin 1 represents another subfamily of E. coli heat-stable toxin.

“…Experiments were done according to Guandalini et al (16). Adult male New Zealand White rabbits (2-3 kg) were anesthetized by methoxyflurane inhalation and sacrificed by air embolism.…”

Rabbit Gastroenterology

“…Bacteria such as Bacteriodes, are associated with exerting an inhibitory effect on potentially pathogenic bacteria including Clostridium and coliforms [48]. Mechanisms for antibiotic associated enteritis include: (1) alteration in intestinal motility and enterocyte ion transport was shown in lincomycin, clindamycin, erythromycin, and gentamicin [49,50]; and (2) altered microbial flora and overgrowth of C difficile and its cytotoxin following to oral ampicillin administration, and C sporogenes and its enterotoxin, following intravenous cephalosporin administration [51,52].…”

Enteric Toxins from Bacteria Colonizing Human Gut

“…It is possible to speculate that the different biological effects of toxins A and B in the animal model (77) are related to the different receptors used by the toxins.…”