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409 Defining The Vulnerable Period for Re-establishment of Clostridium difficile Colonization After Treatment With Oral Vancomycin

Sunday, April 3, 2011
Trinity Ballroom (Hilton Anatole)
Jennifer Cadnum, BS , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Lucy A. Jury, NP , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Michelle M. Nerandzic, BS , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Robin L. Jump, MD, PhD , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Brett M. Sitzlar, BS , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH
Curtis J. Donskey, MD , Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, OH

Background: A significant proportion of patients receiving oral vancomycin for treatment of Clostridium difficile infection (CDI) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined. In theory, this period will extend from the time vancomycin levels reach subinhibitory concentrations to the time when the intestinal microflora recovers sufficiently to inhibit C. difficile growth. 

Objective: To determine the vulnerable period for re-establishment of C. difficile colonization after vancomycin therapy.

Methods: We conducted a 6-month prospective study of all inpatients receiving oral vancomycin for CDI. Stool samples were collected before, during, and after therapy and vancomycin concentrations were measured using AxSymII fluorescence polarization immunoassay. To evaluate for presence of antimicrobial inhibitory activity, we assessed growth of C. difficile inoculated into stool filtrates supplemented with nutrient broth. We examined growth of C. difficile in stool suspensions to assess functional recovery of the microflora (vulnerability to colonization was defined as ≥1 log increase in C. difficile concentration).

Results: Of 82 inpatients receiving oral vancomycin, 48 (59%) had stool samples available for analysis during and after therapy. During therapy, high concentrations of vancomycin were present and growth was suppressed in stool filtrates and suspensions (figure). Inhibitory levels of vancomycin persisted in stool of most patients for 3-4 days after therapy. From 5 to 21 days after therapy, a majority of stool suspensions supported growth of C. difficile, whereas after 21 days most samples were inhibitory.

Conclusions: Our results suggest that there is a vulnerable period for re-establishment of C. difficile colonization after oral vancomycin therapy that begins a few days after discontinuation of treatment and extends for about 3 weeks in most patients.