Impact of β-lactam antibiotic therapeutic drug monitoring on dose adjustments in critically ill patients undergoing continuous renal replacement therapy

Int J Antimicrob Agents. 2017 May;49(5):589-594. doi: 10.1016/j.ijantimicag.2017.01.009. Epub 2017 Mar 21.

Abstract

The objective of this study was to describe the effect of therapeutic drug monitoring (TDM) and dose adjustments of β-lactam antibiotics administered to critically ill patients undergoing continuous renal replacement therapy (CRRT) in a 30-bed tertiary intensive care unit (ICU). β-Lactam TDM data in our tertiary referral ICU were retrospectively reviewed. Clinical, demographic and dosing data were collected for patients administered β-lactam antibiotics while undergoing CRRT. The target trough concentration range was 1-10× the minimum inhibitory concentration (MIC). A total of 111 TDM samples from 76 patients (46 male) with a mean ± standard deviation age of 56.6 ± 15.9 years and weight of 89.1 ± 25.8 kg were identified. The duration of antibiotic therapy was between 2 days and 42 days. TDM identified a need for dose modification of β-lactam antibiotics in 39 (35%) instances; in 27 (24%) samples, TDM values resulted in decreasing the prescribed dose of β-lactam antibiotic whereas an increase in the prescribed dose occurred in 12 (11%) cases. In patients treated for hospital-acquired pneumonia and primary or secondary bacteraemia, the dose was required to be decreased in 10/25 (40%) and 7/46 (15%) cases, respectively, to attain target concentrations. β-Lactam TDM is a useful tool for guiding drug dosing in complex patients such as those receiving CRRT. Although over one-third of patients manifested concentrations outside the therapeutic range, most of these CRRT patients had excessive β-lactam concentrations.

Keywords: Continuous renal replacement therapy; Pharmacodynamics; Pharmacokinetics; TDM; Therapeutic drug monitoring; β-Lactam antibiotic.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Critical Care
  • Critical Illness
  • Cross Infection / drug therapy*
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Intensive Care Units
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pneumonia, Bacterial / drug therapy*
  • Renal Replacement Therapy / methods*
  • Retrospective Studies
  • Tertiary Care Centers
  • Young Adult
  • beta-Lactams / administration & dosage
  • beta-Lactams / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • beta-Lactams