Risk Factors for Systemic Vancomycin Exposure Following Administration of Oral Vancomycin for the Treatment of Clostridium difficile Infection Natasha N. Pettit, 1,2 Daryl D. DePestel, 1,2 Alexander L. Fohl, 1,2 Rachel Eyler, 1,2 and Peggy L. Carver 1,2, * 1 Department of Clinical, Social and Administrative Sciences, University of Michigan College of Pharmacy, Ann Arbor, Michigan; 2 Department of Pharmacy Services, University of Michigan Health System, Ann Arbor, Michigan OBJECTIVE To identify risk factors for systemic exposure to vancomycin (VAN) following administra- tion of oral vancomycin (POV) for the treatment of Clostridium difficile infection (CDI). DESIGN Prospective, observational, single-center case series. SETTING Academic medical center. PATIENTS Hospitalized patients with suspected or confirmed CDI who received POV for at least 5 days. INTERVENTION Random VAN serum levels were obtained on days 5, 10, and weekly thereafter in patients treated for ≥ 5 days with POV without concomitant intravenous VAN. MEASUREMENTS AND RESULTS Of 117 random VAN serum levels from 85 patients, 58 patients (68.2%) had one or more detectable (≥ 0.05 lg/ml) levels and 15 (17.6%) of 85 patients had one or more levels > 2.5 lg/ml. Risk factors for detectable VAN exposure following administration of POV included POV dosages > 500 mg/day (odds ratio [OR] 35.83, 95% confidence interval [CI] 7.56–169.8), the presence of severe CDI (OR 4.11, 95% CI 2.76–10.83, p=0.028), intensive care unit (ICU) admission (OR 3.80, 95% CI 1.02–14.21, p=0.032), and the administration of POV ≥ 10 days (OR 6.71, 95% CI 1.81– 24.83, p=0.0025). Risk factors for exposure to serum VAN concentrations > 2.5 lg/ml included the presence of gastrointestinal (GI) pathology (OR 5.22, 95% CI 3.45–18.3, p=0.031), ICU admission (OR 3.21, 95% CI 1.40–10.28, p=0.022), the use of VAN retention enemas (OR 4.73, 95% CI 2.42– 20.39, p=0.036), and having a creatinine clearance ≤ 50 ml/minute or undergoing hemodialysis or continuous renal replacement therapy (OR 4.03, 95% CI 1.26–12.84, p=0.039). CONCLUSIONS Serum VAN levels were detected in 58 (68.2%) of 85 patients receiving POV for CDI. Risk factors for systemic exposure to VAN following administration of POV included ICU admission; VAN dosages > 500 mg/day; administration ≥ 10 days or as retention enemas; and the presence of severe CDI, renal dysfunction, or inflammatory conditions of the GI tract. Unique to our study, we identified ICU admission and the concomitant use of VAN retention enemas to be significant risk factors for systemic exposure to VAN. KEY WORDS vancomycin retention enemas, intestinal absorption, biologic availability. (Pharmacotherapy 2015;35(2):119–126) doi: 10.1002/phar.1538 Funding: This study was carried out as part of our routine quality assurance work. This work was supported by internal funding. This work was previously presented at IDWeek: A Joint Meeting of IDSA, SHEA, HIVMA, and PIDS, San Diego, CA, Octo- ber 17–21, 2012. Abstract 1637, but has otherwise not been published, nor submitted for publication elsewhere. * Address for correspondence: Peggy L. Carver, Department of Clinical, Social and Administrative Sciences, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109-1063; e-mail: peg@med.umich.edu. Ó 2015 Pharmacotherapy Publications, Inc. O RIGINAL R ESEARCH A RTICLES