An alterative pathophysiological mechanism other than the toxin production of K. oxytoca in inducing colitis cannot be ruled out by this study. However, taken together with the typical histological features of toxin-induced colitis seen in AAHC and in colitis induced by K. oxytoca in animal models of this disease (10), citation the current results support the hypothesis that the K. oxytoca cytotoxin is associated with AAHC. Future studies need to clarify this issue. Cytotoxic effects of K. oxytoca isolates from AAHC patients were reported previously (1, 8, 10, 15-17). To date, however, those reports were not extended to include other Klebsiella species or K. oxytoca strains from infections of other organs.

An important finding of the current study was that the majority of toxin-positive strains were obtained from stool cultures regardless of whether they were isolated from symptomatic or asymptomatic carriers. Accordingly, we propose that K. oxytoca should not be viewed as a naive constituent of the normal bowel microflora, in contrast to other Klebsiella species. Given its capacity to induce AAHC, resident K. oxytoca should be classified as an opportunistic pathogen that is able to induce disease under certain circumstances, such as an alteration of the normal colonic microflora due to antibiotic treatment and the subsequent overgrowth of the toxin-producing bacterium (5). This proposal is supported by the finding that despite the fact that a high proportion of isolates originating from asymptomatic carriers showed cytotoxicity, their amounts in stools were significantly lower than amounts in stools from symptomatic patients (<101 CFU/ml compared to 4 �� 106 CFU/ml for AAHC patients) (23).

The coresidence of toxin-positive and toxin-negative isolates in patients and in healthy individuals is consistent with the hypothesis that colitis may result from toxin production during the outgrowth of these strains following antibiotic treatment. Moreover, for the patient group with acute or chronic diarrheal diseases, more than half of the isolates were cytotoxin positive. Thus, the role of cytotoxin-producing K. oxytoca in intestinal disease other than AAHC will require further investigation (23). Interestingly, cytotoxicity was also detected for a large proportion of skin isolates, which were derived primarily from foot ulcers.

These wound infections are thought to be derived via fecal contamination Drug_discovery (2). None of the isolates originating from typical Klebsiella infection sites, i.e., the urinary and respiratory tracts, showed a cytotoxic phenotype. Two isolates from bloodstream infections were cytotoxin positive: one was isolated from a patient with CRBSI, and the second was obtained from a patient with cholangitis. It is reasonable to propose that the origin of these infection-causing strains was the skin or intestine. In summary, we found that cytotoxin-positive K.