title: Conserving antibiotics for the future: new ways to use old and new drugs from a pharmacokinetic and pharmacodynamic perspective.
abstract: There is a growing need to optimize the use of old and new antibiotics to treat serious as well as less serious infections. The topic of how to use pharmacokinetic and pharmacodynamic (PK/PD) knowledge to conserve antibiotics for the future was elaborated on in a workshop of the conference (The conference "The Global Need for Effective Antibiotics - moving towards concerted action", ReAct, Uppsala, Sweden, 2010). The optimization of dosing regimens is accomplished by choosing the dose and schedule that results in the antimicrobial exposure that will achieve the microbiological and clinical outcome desired while simultaneously suppressing emergence of resistance. PK/PD of antimicrobial agents describe how the therapeutic drug effect is dependent on the potency of a drug against a microorganism and the exposure (the concentration of antimicrobial available for effect over time). The description and modeling of these relationships quantitatively then allow for a rational approach to dose optimization and several strategies to that purpose are described. These strategies include not only the dosing regimen itself but also the duration of therapy, preventing collateral damage through inappropriate use and the application of PK/PD in drug development. Furthermore, PK/PD relationships of older antibiotics need to be urgently established. The need for global harmonization of breakpoints is also suggested and would add efficacy to antibiotic therapy. For each of the strategies, a number of priority actions are provided.
authors: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, The Netherlands. jwmouton@gmail.com
authors: Johan W
authors: JW
authors: Mouton
authors: Paul G
authors: PG
authors: Ambrose
authors: Rafael
authors: R
authors: Canton
authors: George L
authors: GL
authors: Drusano
authors: Stephan
authors: S
authors: Harbarth
authors: Alasdair
authors: A
authors: MacGowan
authors: Ursula
authors: U
authors: Theuretzbacher
authors: John
authors: J
authors: Turnidge
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests / Q000379:methods; D008954:Models, Biological; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents