Optimization of linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis

Future Microbiol. 2017 Jan:12:39-50. doi: 10.2217/fmb-2016-0140. Epub 2016 Dec 6.

Abstract

Aim: To optimize linezolid treatment regimens for Gram-positive bacterial infections based on pharmacokinetic/pharmacodynamic analysis.

Materials & methods: The minimum inhibitory concentration (MIC) distribution of 572 Gram-positive strains from patients with clinically confirmed infections was analyzed. Using the Monte Carlo simulation method, the cumulative fraction of response and probability of target attainment were determined for linezolid regimens of 600 mg q.12h and q.8h Results: Linezolid dosage of 600 mg q.12h yielded >90% cumulative fraction of response and probability of target attainment for staphylococcal infections with an MIC of ≤1 mg/l, enterococcal infections with higher MIC values required 600 mg q.8h.

Conclusion: Linezolid 600 mg q.12h is still the clinically recommended empirical dosage for Gram-positive bacterial infections. However, as bacterial MICs increase, 600 mg q.8h may be required to achieve better efficacy.

Keywords: Gram-positive bacteria; Monte Carlo simulation; linezolid; pharmacokinetic/pharmacodynamic analysis.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use*
  • Asian People
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial
  • Enterococcus faecalis / drug effects
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Linezolid / pharmacokinetics*
  • Linezolid / therapeutic use*
  • Male
  • Microbial Sensitivity Tests
  • Monte Carlo Method
  • Prospective Studies
  • Staphylococcal Infections / drug therapy

Substances

  • Anti-Bacterial Agents
  • Linezolid