title: Use of old antibiotics now and in the future from a pharmacokinetic/pharmacodynamic perspective.
abstract: Because of the increase in bacterial resistance to commonly used antibacterial drugs, old antibiotics are being 'revived' and, once again, are attracting interest. Many of these old antibiotics were approved long ago, in an era when there was no clear process for development, and requirements for efficacy to be demonstrated in rigorous clinical trials did not exist. At the time of these approvals, pharmacokinetic and pharmacodynamic principles were largely unknown, and did not inform the dose-finding process or recommendations for optimal usage. Indeed, the task of generating basic vital information for these old antibiotics remains to be performed. In this review, we provide a brief overview of the most essential data needed for dose justification and optimization. An overview of the shortage of data for selected old antibiotics illustrates the scope of the problem. In order to prevent harming patients with clinical decisions based on inadequate evidence, a redevelopment procedure for old antibiotics is urgently needed, including a regulatory framework.
authors.affiliation: Department of Medical Microbiology, Medical Centre Haaglanden (MCH), The Hague, The Netherlands.
authors.forename: A E
authors.initials: AE
authors.lastname: Muller
authors.affiliation: Centre for Anti-infective Agents, Vienna, Austria.
authors.forename: U
authors.initials: U
authors.lastname: Theuretzbacher
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands; Department of Medical Microbiology, Radboudumc, Nijmegen, The Netherlands. Electronic address: jwmouton@gmail.com.
authors.forename: J W
authors.initials: JW
authors.lastname: Mouton
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001424:Bacterial Infections / Q000188:drug therapy*; D017277:Drug Approval; D024901:Drug Resistance, Multiple, Bacterial; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents
keywords: Dose optimization; PK/PD; effectiveness; registration; revived antibiotics