Clostridium difficile infection (CDI) is increasingly found in children worldwide, but limited data are available from children living in southern Europe. A 6-year retrospective study was performed to investigate the epidemiology, clinical features, treatment, and risk of recurrence in Italy. Data of children with community- and hospital-acquired CDI (CA-CDI and HA-CDI, respectively) seen at seven pediatric referral centers in Italy were recorded retrospectively. Annual infection rates/10,000 hospital admissions were calculated. Logistic regression was used to investigate risk factors for recurrence. A total of 177 CDI episodes was reported in 148 children (83 males, median age 55.3 months), with a cumulative infection rate of 2.25/10,000 admissions, with no significant variability over time. The majority of children (60.8 %) had CA-CDI. Children with HA-CDI (39.2 %) had a longer duration of symptoms and hospitalization (p = 0.003) and a more common previous use of antibiotics (p = 0.0001). Metronidazole was used in 70.7 % of cases (87/123) and vancomycin in 29.3 % (36/123), with similar success rates. Recurrence occurred in 16 children (10.8 %), and 3 (2 %) of them presented a further treatment failure. The use of metronidazole was associated with a 5-fold increase in the risk of recurrence [odds ratio (OR) 5.18, 95 % confidence interval (CI) 1.1–23.8, p = 0.03]. Short bowel syndrome was the only underlying condition associated with treatment failure (OR 5.29, 95 % CI 1.17–23.8, p = 0.03). The incidence of pediatric CDI in Italy is low and substantially stable. In this setting, there is a limited risk of recurrence, which mainly concerns children treated with oral metronidazole and those with short bowel syndrome.

Clostridium difficile infection in children: epidemiology and risk of recurrence in a low-prevalence country

Toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT) produced by Clostridium difficile (CD) are thought to play a key role in inducing diarrhea. The aim of this study was to investigate the individual and combined roles of CD toxins in inducing enterotoxic and cytotoxic effect. Ion secretion and epithelial damage were evaluated in the Ussing chambers as measure of enterotoxic or cytotoxic effect, respectively, in human-derived intestinal cells. When added to the mucosal side of Caco-2 cells, TcdB, but not TcdA, induced ion secretion and its effects increased in the presence of TcdA. CDT also induced ion secretion when added to either the mucosal or serosal compartment. Serosal addition of TcdB induced epithelial damage consistent with its cytotoxic effect. However, mucosal addition of TcdB had similar effects, but only in the presence of TcdA. CDT induced epithelial damage when added to the serosal side of cell monolayers, and this was associated with a late onset but prolonged effect. All data were replicated using human colon biopsies. These data indicate that CD, through the combined and direct activity of its three toxins, induces integrated and synergic enterotoxic and cytotoxic effects on the intestinal epithelium.

/pdf/differential-effects-of-clostridium-difficile-toxins-on-ion-2c4ny7j6q6.pdf

Differential effects of Clostridium difficile toxins on ion secretion and cell integrity in human intestinal cells.

Monoclonal antibodies against Clostridium difficile infection in the pipeline

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Monoclonal antibodies against Clostridium difficile infection in the pipeline