Towards precision medicine: Therapeutic drug monitoring-guided dosing of vancomycin and β-lactam antibiotics to maximize effectiveness and minimize toxicity

Am J Health Syst Pharm. 2020 Jul 7;77(14):1104-1112. doi: 10.1093/ajhp/zxaa128.

Abstract

Purpose: The goal of this review is to explore the role of antimicrobial therapeutic drug monitoring (TDM), especially in critically ill, obese, and older adults, with a specific focus on β-lactams and vancomycin.

Summary: The continued rise of antimicrobial resistance prompts the need to optimize antimicrobial dosing. The aim of TDM is to individualize antimicrobial dosing to achieve antibiotic exposures associated with improved patient outcomes. Initially, TDM was developed to minimize adverse effects during use of narrow therapeutic index agents. Today, patient and organism complexity are expanding the need for precision dosing through TDM services. Alterations of pharmacokinetics and pharmacodynamics (PK/PD) in the critically ill, obese, and older adult populations, in conjunction with declining organism susceptibility, complicate attainment of therapeutic targets. Over the last decade, antimicrobial TDM has expanded with the emergence of literature supporting β-lactam TDM and a shift from monitoring vancomycin trough concentrations to monitoring of the ratio of area under the concentration (AUC) curve to minimum inhibitory concentration (MIC). PK/PD experts should be at the forefront of implementing precision dosing practices.

Conclusion: Precision dosing through TDM is expanding and is especially important in populations with altered PK/PD, including critically ill, obese, and older adults. Due to wide PK/PD variability in these populations, TDM is vital to maximize antimicrobial effectiveness and decrease adverse event rates. However, there is still a need for studies connecting TDM to patient outcomes. Providing patient-specific care through β-lactam TDM and transitioning to vancomycin AUC/MIC monitoring may be challenging, but with experts at the forefront of this initiative, PK-based optimization of antimicrobial therapy can be achieved.

Keywords: aged; beta-lactams; critical illness; drug monitoring; obesity; vancomycin.

Publication types

  • Review

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Area Under Curve
  • Critical Illness
  • Dose-Response Relationship, Drug
  • Drug Monitoring / methods*
  • Drug Resistance, Bacterial
  • Humans
  • Obesity / complications
  • Precision Medicine
  • Vancomycin / administration & dosage*
  • Vancomycin / adverse effects
  • Vancomycin / pharmacokinetics
  • beta-Lactams / administration & dosage*
  • beta-Lactams / adverse effects
  • beta-Lactams / pharmacokinetics

Substances

  • Anti-Bacterial Agents
  • beta-Lactams
  • Vancomycin