Risk factors for systemic vancomycin exposure following administration of oral vancomycin for the treatment of Clostridium difficile infection.

Abstract

To identify risk factors for systemic exposure to vancomycin (VAN) following administration of oral vancomycin (POV) for the treatment of Clostridium difficile infection (CDI). Prospective, observational, single-center case series. Academic medical center. Hospitalized patients with suspected or confirmed CDI who received POV for at least 5days. Random VAN serum levels were obtained on days 5, 10, and weekly thereafter in patients treated for ≥5days with POV without concomitant intravenous VAN. Of 117 random VAN serum levels from 85 patients, 58 patients (68.2%) had one or more detectable (≥0.05μg/ml) levels and 15 (17.6%) of 85 patients had one or more levels >2.5μg/ml. Risk factors for detectable VAN exposure following administration of POV included POV dosages >500mg/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 ≥10days (OR 6.71, 95% CI 1.81-24.83, p=0.0025). Risk factors for exposure to serum VAN concentrations >2.5μg/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 ≤50ml/minute or undergoing hemodialysis or continuous renal replacement therapy (OR 4.03, 95% CI 1.26-12.84, p=0.039). 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 >500mg/day; administration ≥10days 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.