Healthcare resource utilization for recurrent Clostridium difficile infection in a large university hospital in Houston, Texas.

BACKGROUND: There are limited data examining healthcare resource utilization in patients with recurrent Clostridium difficile infection (CDI). METHODS: Patients with CDI at a tertiary-care hospital in Houston, TX, were prospectively enrolled into an observational cohort study. Recurrence was assessed via follow-up phone calls. Patients with one or more recurrence were included in this study. The location at which healthcare was obtained by patients with recurrent CDI was identified along with hospital length of stay. CDI-attributable readmissions, defined as a positive toxin test within 48 hours of admission and a primary CDI diagnosis, were also assessed. RESULTS: 372 primary cases of CDI were identified of whom 64 (17.2%) experienced at least one CDI recurrence. Twelve of 64 patients experienced 18 further episodes of CDI recurrence. Of these 64 patients, 33 (50.8%) patients with recurrent CDI were readmitted of which 6 (18.2%) required ICU care, 29 (45.3%) had outpatient care only, and 2 (3.1%) had an ED visit. Nineteen (55.9%) readmissions were defined as CDI-attributable. For patients with CDI-attributable readmission, the average length of stay was 6 ± 6 days. CONCLUSION: Recurrent CDI leads to significant healthcare resource utilization. Methods of reducing the burden of recurrent CDI should be further studied.

Variable isoflavone content of red clover products affects intestinal disposition of biochanin A, formononetin, genistein, and daidzein.

BACKGROUND: Marketed red clover (Trifoleum pratense) products use a wide variety of labels, and the isoflavone content from the label is ambiguous. MATERIALS AND METHODS: In the present study, we analyzed the content of various isoflavone products, and determined (1) the content and (2) how the sample matrix of red clover products affects the intestinal disposition of main isoflavones within it, using the human intestinal Caco-2 cell model. RESULTS: Analysis using high- and ultraperformance liquid chromatography indicates that the isoflavone content varied significantly (p < 0.05) between the chosen products. Consequently, rates of isoflavone absorption across the Caco-2 cell monolayers varied (p < 0.05) greatly. Unexpectedly, permeabilities of biochanin A and formononetin (two key biomarkers) were found to be significantly affected (p < 0.05) by the product matrix. As expected, biochanin A was the only isoflavone with noticeable metabolite peaks in both the apical and basolateral sides. Interestingly, rates of metabolism and the polarity of the glucuronidated biochanin A excretion were also significantly altered (p < 0.05) by the product matrix. Studies using the breast cancer resistance protein (BCRP) inhibitor, dipyridamole, showed that both the apical and basolateral excretion of biochanin A glucuronides were significantly (p < 0.05) reduced (7.5- and 9.4-fold, respectively) when dipyridamole is present. This provides evidence that BCRP is the main transporter responsible for the apical efflux of isoflavone glucuronides. CONCLUSIONS: The isoflavone content of the marketed red clover products is highly variable, and the product matrix significantly affected the intestinal disposition of red clover isoflavones by altering their absorption rates, permeabilities, biochanin A glucuronide excretion rates, and the polarity of biochanin A glucuronide excretion. This research provides scientific evidence to support the standardization effort, so that consumers can make intelligent product choices.

Disposition of flavonoids via enteric recycling: enzyme stability affects characterization of prunetin glucuronidation across species, organs, and UGT isoforms.

We characterized the in vitro glucuronidation of prunetin, a prodrug of genistein that is a highly active cancer prevention agent. Metabolism studies were conducted using expressed human UGT isoforms and microsomes/S9 fractions prepared from intestine and liver of rodents and humans. The results indicated that human intestinal microsomes were more efficient than liver microsomes in glucuronidating prunetin, but rates of metabolism were dependent on time of incubation at 37 degrees C. Human liver and intestinal microsomes mainly produced metabolite 1 (prunetin-5- O-glucuronide) and metabolite 2 (prunetin-4'- O-glucuronide), respectively. Using 12 human UGT isoforms, we showed that UGT1A7, UGT1A8, and UGT1A9 were mainly responsible for the formation of metabolite 1, whereas UGT1A1, UGT1A8, and UGT1A10 were mainly responsible for the formation of metabolite 2. This isoform-specific metabolism was consistent with earlier results obtained using human liver and intestinal microsomes, as the former (liver) is UGT1A9-rich whereas the latter is UGT1A10-rich. Surprisingly, we found that the thermostability of the microsomes was isoform- and organ-dependent. For example, human liver microsomal UGT activities were much more heat-stable (37 degrees C) than intestinal microsomal UGT activities, consistent with the finding that human UGT1A9 is much more thermostable than human UGT1A10 and UGT1A8. The organ-specific thermostability profiles were also evident in rat microsomes and mouse S9 fractions, even though human intestinal glucuronidation of prunetin differs significantly from rodent intestinal glucuronidation. In conclusion, prunetin glucuronidation is species-, organ-, and UGT-isoform-dependent, all of which may be impacted by the thermostability of specific UGT isoforms involved in the metabolism.