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Background: Clostridium difficile colitis is associated with increased age, antibiotic usage, and hospitalization. Severe C. difficile colitis refractory to medical therapy may require surgical intervention including subtotal colectomy. We initiated an adjuvant intracolonic vancomycin (ICV) enema protocol for inpatients with severe C. difficile colitis and compared the response to this therapy in patients from the community and nursing homes., Methods: A single-hospital, retrospective chart review was done on 47 consecutive patients with C. difficile colitis treated with ICV (1 g/500 mL normal saline q6h) from January 2007 through October 2009. The proportions of patients with the outcomes of response to the ICV protocol, need for subtotal colectomy, and death were described. Associations of patient characteristics with these outcomes were examined with bivariate tests and multivariable logistic models with adjustment for age, hypoalbuminemia, acidosis, and nursing-home status., Results: Thirty-three of 47 patients (70%) with severe C. difficile colitis responded to adjunct ICV with complete resolution without surgery. Incomplete responders who had surgery were more likely to survive than those patients who did not undergo subtotal colectomy (p<0.01). Seven of nine patients who underwent surgery survived >90 d, and overall, 37 of 47 patients (79%) survived after ICV therapy. Nursing-home residence, acidosis, and hypoalbuminemia were significantly associated with the non-resolution of colitis in bivariate analyses (all p<0.01), whereas nursing-home residence and hypoalbuminemia showed non-significant trends toward association with death (p=0.07 and p=0.06, respectively). Multivariate logistic-regression models showed significant associations of acidosis with an incomplete response to ICV (p=0.02), of older age with death (p=0.04), and of hypoalbuminemia with both an incomplete response to ICV and death (both p=0.04). No complications were attributable to ICV., Conclusion: Complete resolution without surgery was achieved in 70% in this series of patients with severe C. difficile colitis who received adjunct ICV therapy. A clinical trial will be needed to determine whether ICV as compared with standard therapy alone can reduce the need for surgery with non-inferior or superior outcomes.

Objective: To determine the effect of WBC accumulation on the concentration of enrofloxacin in inflamed tissues in dogs., Animals: 6 adult Bloodhounds., Procedures: Dogs were instrumented bilaterally with tissue chambers. Peripheral WBCs collected from each dog were exposed in vitro to radiolabeled enrofloxacin ((14)C-ENR). Inflammation was induced with carrageenan in 1 chamber. Ten hours later, treated cells were administered IV to each dog such that (14)C-ENR was delivered at a mean +/- SD dosage of 212 +/- 43 microg. Samples of extracellular fluid from inflammation and control chambers and circulating blood were then collected before (baseline) and for 24 hours after WBCs were administered. Samples were centrifuged to separate WBCs from plasma (blood) or chamber fluid. Radiolabeled enrofloxacin was scintigraphically detected and pharmacokinetically analyzed. Comparisons were made between extra- and intracellular chamber fluids by use of a Student paired t test., Results: (14)C-ENR was not detectable in plasma, peripheral WBCs, control chambers, or baseline samples from inflammation chambers. However, (14)C-ENR was detected in extra- cellular fluid from inflammation chambers (mean +/- SD maximum concentration, 2.3 +/- 0.5 ng/mL) and WBCs (maximum concentration, 7.7 +/- 1.9 ng/mL). Mean disappearance half-life of (14)C-ENR from extracellular fluid and WBCs from inflammation chambers was 26 +/- 10 hours and 17 +/- 6 hours, respectively., Conclusions and Clinical Relevance: WBCs were responsible for the transport and release of (14)C-ENR at sites of inflammation. Accumulation of drug by WBCs might increase the concentration of drug at the site of infection, thus facilitating therapeutic success.

Concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were detected in tissues following single intravenous administration of 20 mg/kg to four anesthetized dogs. Two hours after treatment, serum samples were collected, animals were euthanized, and tissues were collected from each dog. Solid tissues were homogenized, and both enrofloxacin and ciprofloxacin were detected using high-performance liquid chromatography. Enrofloxacin was detected in all tissues examined; the highest concentrations were found in the gall bladder, urine, bile, stomach, and liver. Concentrations in the cerebral cortex, cerebrospinal fluid, skin, and prostate were 5.7, 5.3, 9.2, and 23.5 microg/ml, respectively. Tissues for which the concentration of enrofloxacin was 4 microg/ml or lower included the trachea, articular cartilage, aqueous humor, fat, and tendon. An inhibitory quotient of 8 or more was achieved for enrofloxacin in the majority of tissues studied. Ciprofloxacin was detected in 29 of 40 tissues examined.