title: Effective suppression of vancomycin-resistant Enterococcus species in asymptomatic gastrointestinal carriers by a novel glycolipodepsipeptide, ramoplanin.
abstract: Nosocomial bloodstream infections due to vancomycin-resistant enterococci (VRE) are associated with increased morbidity rates, mortality rates, and hospitalization costs. Gastrointestinal carriage of VRE is an important risk factor for subsequent infections. This 3-arm, phase II, double-blinded, randomized, multicenter, placebo-controlled study evaluated the safety and efficacy of oral ramoplanin (a novel, nonabsorbed glycolipodepsipeptide) versus placebo for suppression of gastrointestinal VRE colonization. Sixty-eight patients who were colonized with VRE were enrolled and received 2 daily doses of ramoplanin (100 mg or 400 mg) or placebo orally for 7 days. The primary end point was the proportion of persons per group from whom VRE were not recovered (VRE-free) on days 7, 14, and 21 after screening. After treatment, VRE-free status was as follows: day 7, none of the 20 patients in the placebo group, and 17 of 21 (P<.001) and 18 of 20 (P<.001) in the 100-mg and 400-mg ramoplanin groups, respectively; on day 14, 2 of 20 patients in the placebo group, and 6 of 21 (P=.134) and 7 of 17 (P=.028), in the 100-mg and 400-mg ramoplanin groups, respectively. By day 21, there were no differences between treatment groups. Adverse events were similar for all treatment groups. Ramoplanin was safe and effective in temporarily suppressing gastrointestinal VRE carriage.
authors.affiliation: Department of Internal Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia, USA. mwong@caregroup.harvard.edu
authors.forename: M T
authors.initials: MT
authors.lastname: Wong
authors.forename: C A
authors.initials: CA
authors.lastname: Kauffman
authors.forename: H C
authors.initials: HC
authors.lastname: Standiford
authors.forename: P
authors.initials: P
authors.lastname: Linden
authors.forename: G
authors.initials: G
authors.lastname: Fort
authors.forename: H J
authors.initials: HJ
authors.lastname: Fuchs
authors.forename: S B
authors.initials: SB
authors.lastname: Porter
authors.forename: R P
authors.initials: RP
authors.lastname: Wenzel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002353:Carrier State / Q000382:microbiology*; D003257:Consumer Product Safety; D047630:Depsipeptides; D004064:Digestive System / Q000382:microbiology*; D004311:Double-Blind Method; D016983:Enterococcus / Q000187:drug effects* / Q000302:isolation & purification; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010456:Peptides, Cyclic; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C041438:ramoplanin