Does guideline-based dosing of beta lactam antibiotics and vancomycin achieve the target drug concentrations more than therapeutic drug monitoring-based dosing in critically ill patients? (GUIDE TRIAL)

The primary aim of the GUIDE TRIAL is to determine whether locally endorsed guideline based antibiotic dosing achieves pharmacodynamic target attainment of 100% fT>MIC for beta lactam antibiotics, or a steady state trough concentration of 15-20mg/L for vancomycin in critically ill patients. The GUIDE TRIAL is a single centred, prospective, observational study in critically ill patients admitted to the ICU with infections treated with the study antibiotics (piperacillin/tazobactam, flucloxacillin, meropenem, cefepime and vancomycin). All patients admitted over a 12 month period who meet the inclusion criteria are eligible for inclusion. The local guideline titled ‘Antibiotic dosing, Critical Care’ is published as a guideline on the Hospital and Health Service intranet site. A manuscript describing the development of this guideline is currently under review in a peer-reviewed journal. The guideline was compiled from the primary literature and dosing regimens were selected by author consensus based on the available evidence. Briefly, the guideline sought to provide clinicians with a dosing nomogram based on renal function, continuous renal replacement therapy, and suspected augmented renal clearance. Information regarding pharmacokinetics, pharmacodynamics, drug penetration in site of action and minimum inhibitory concentration clinical breakpoints were aimed for inclusion. The local guideline is endorsed by the hospital and health service and used in practice currently in the ICU, therefore this study reflects current prescribing practices in the ICU and no interventions or exposures included in this study. Patients prescribed beta lactams and vancomycin will require 4 blood samples to be taken (2 samples taken during day 1-3 of therapy, and 2 samples taken on day 4-6 of therapy). Samples are required to be taken at both 50% of the dosing interval and at 100% of the dosing interval. The duration of observations will be a maximum of six days.