Optimal tigecycline dosage regimen is urgently needed: results from a pharmacokinetic/pharmacodynamic analysis of tigecycline by Monte Carlo simulation

Int J Infect Dis. 2014 Jan:18:62-7. doi: 10.1016/j.ijid.2013.09.008. Epub 2013 Oct 24.

Abstract

Background: The number of reported cases of resistance to tigecycline is increasing. The aim of this study was to evaluate the current standard tigecycline dosage regimen from a pharmacokinetic/pharmacodynamic (PK/PD) perspective.

Methods: Pharmacokinetic parameters and microbiological data were analyzed by Monte Carlo simulation in an evaluation of effectiveness.

Results: Tigecycline exhibits excellent in vitro antimicrobial activity, however the standard tigecycline dosing regimen fails to achieve the best outcome in vivo for the common drug-resistant strains, including Acinetobacter baumannii, Enterobacter spp, and Klebsiella pneumoniae. This may result in a lack of response to tigecycline therapy or to a further increase in the resistance rate.

Conclusions: In the absence of new drugs on the horizon, rather than using a single fixed dosing regimen, tigecycline dosing needs to be optimized in order to achieve the desired successful clinical response and to prevent an escalation in drug resistance.

Keywords: Monte Carlo simulation; Optimal dosage regimen; Pharmacokinetic/pharmacodynamic analysis; Tigecycline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Enterobacter / drug effects
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Microbial Sensitivity Tests
  • Minocycline / administration & dosage
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacokinetics
  • Monte Carlo Method
  • Tigecycline

Substances

  • Anti-Bacterial Agents
  • Tigecycline
  • Minocycline