title: Improved treatment of multidrug-resistant bacterial infections: utility of clinical studies.
abstract: In a time of increasing antibacterial resistance and limited availability of new antibiotics, clinical studies are much needed to assess treatment options against multidrug-resistant organisms (MDROs). In this review, we describe the clinical challenge caused by MDROs and present recent evidence on how clinical studies may generate quality data to improve antibiotic treatment of MDRO infections. To this aim, we critically assess the current status, gaps and challenges associated with observational and interventional studies performed to assess MDRO treatment options. We address why observational studies are useful, which treatment options for MDRO have been explored by observational studies and how to improve quality and usefulness of observational studies. Furthermore, the utility of clinical pharmacokinetic/pharmacodynamic studies for improving MDRO treatment is described. Finally, we discuss interventional study designs, end points and margins, as well as ethical, logistic and statistical challenges, and current regulatory changes proposed to foster the development of new antibiotics.
authors.affiliation: Infection Control Program, University of Geneva Hospitals & Faculty of Medicine, Geneva, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Bettiol
authors.forename: Wouter C
authors.initials: WC
authors.lastname: Rottier
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Del Toro
authors.forename: Stephan
authors.initials: S
authors.lastname: Harbarth
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Bonten
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents
keywords: antibacterial resistance; antibacterial treatment; clinical trials; epidemiology; interventional; multidrug-resistant organisms; observational; pharmacokinetic/pharmacodynamic; regulatory guidance; study design