title: Evolution of interventional vancomycin trials in light of new antibiotic development in the USA, 1999-2012.
abstract: Use of vancomycin has increased following the emergence of resistant Gram-positive bacterial infections. Investigation into recent vancomycin clinical studies provides insight into the optimal use of vancomycin and the development of novel antibiotics for the treatment of resistant infections. Interventional vancomycin trials registered in ClinicalTrials.gov from January 1999 to December 2012 were identified. Trial trends and characteristics were evaluated in the context of vancomycin use and new antibiotic development. Overall, 122 interventional vancomycin trials were identified, with a significant increase in the number of registered trials per year (P<0.001). The top three indications studied were skin and soft-tissue infections (28.7%), Clostridium difficile infections (13.1%) and surgical prophylaxis (12.3%). Trials testing vancomycin as an experimental agent differed from trials using vancomycin as an active comparator. Experimental agent trials commonly investigated new formulations, dosing regimen optimisation and combination therapy, which were less likely to be in phase 2 or 3 (25% vs. 70%; P<0.001), adopt a randomisation procedure (70% vs. 98%; P<0.001), report results (15% vs. 35%; P=0.02) or be funded by industry (8% vs. 76%; P<0.001). Active comparator trials mainly focused on monotherapy, which led to six FDA-approved drug products and ten investigational new drugs in late-phase development. This study demonstrated a significant increase in interventional vancomycin trials and its recent success, which resulted in several novel agents against resistant Gram-positive bacteria. Further studies are warranted to determine how these agents can best be incorporated within clinical practice.
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Balch
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Spigarelli
authors.affiliation: Division of Clinical Pharmacology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA. Electronic address: catherine.sherwin@hsc.utah.edu.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D004363:Drug Utilization / Q000706:statistics & numerical data; D006801:Humans; D014481:United States; D014640:Vancomycin / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Antibiotics; Clinical trials; Drug development; Vancomycin