Tolevamer, a Novel Nonantibiotic Polymer, Compared with Vancomycin in the Treatment of Mild to Moderately Severe Clostridium difficile-Associated Diarrhea

作者：Thomas Louie, Jennifer Peppe, Chi‐Leung Watt, David A. Johnson, Rezika Mohammed, Garrett T. Dow, K.H. Weiss, Stacey L. Simon, Joseph F. John, Gary E Garber, Samantha Taber, David M. Davidson, the Tolevamer Study Investigator Group · 发表于：Clinical Infectious Diseases · 年份：2006 · DOI：10.1086/506349 · 被引用次数：204 · 研究领域：Clostridium difficile and Clostridium perfringens research、Antimicrobial agents and applications、Nosocomial Infections in ICU

BACKGROUND: Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS: In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS: In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day ...