Improving peak concentrations of a single dose regime of gentamicin in patients with sepsis in the emergency department

PLoS One. 2019 Jan 22;14(1):e0210012. doi: 10.1371/journal.pone.0210012. eCollection 2019.

Abstract

Objective: To achieve an optimal effect in patients with sepsis at the emergency department (ED), the gentamicin peak-concentration should be sufficiently high (i.e. peak-concentration/MIC ≥8-10). ICU patients with sepsis often need higher gentamicin doses to achieve sufficiently high peak-concentrations. The aim of this study is to investigate which dose is needed to reach adequate peak-concentrations in patients presenting with sepsis at the ED.

Methods: Patients with sepsis at the ED were included from August 2015 until February 2017. Peak-concentrations were measured in blood 30 minutes after the first gentamicin dose. The study consisted of three phases. In the first phase, peak-concentrations were measured after a standard dose of 5mg/kg. In the second phase, a simulation ((peak-concentration/actual dose) × simulated dose) was performed to determine which dose was needed to reach adequate gentamicin peak-concentrations of ≥16mg/L. In the third phase, peak-concentrations were measured for the best simulated dose.

Results: In phase one, of 86 patients who received a dose of 5mg/kg, 34 (39.5%) patients did not reach the target peak-concentration of ≥16mg/L, and 73 (84.9%) did not reach ≥20mg/L. In phase two, the simulation showed that with a dose of 7mg/kg 83 (96.5%) patients would reach peak-concentrations ≥16mg/L, and 67 (77.9%) of ≥20mg/L. In phase three, 53 patients received a dose of 7mg/kg, of whom 45 (84.9%) reached peak-concentrations of ≥16mg/L, and 31 (58.5%) of ≥20mg/L.

Conclusion: Patients with sepsis at the ED need higher doses of gentamicin. A dose of 7mg/kg is needed to achieve adequate peak-concentrations in the majority of patients.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics
  • Anti-Bacterial Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Emergency Service, Hospital*
  • Female
  • Gentamicins / administration & dosage
  • Gentamicins / pharmacokinetics
  • Gentamicins / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Sepsis / blood
  • Sepsis / drug therapy*

Substances

  • Anti-Bacterial Agents
  • Gentamicins

Grants and funding

The authors received no specific funding for this work.