A biomarker-based exclusion of ventilator-associated pneumonia : towards improved antibiotic stewardship

Abstract

Ventilator-associated pneumonia (VAP) is a common complicating condition amongst patients mechanically ventilated in the Intensive Care Unit (ICU). It is a common reason for antibiotics to be administered. The diagnosis of VAP is challenging and amongst patients in whom VAP is suspected, approximately a third will have infection confirmed. Therefore many patients receive antibiotics for VAP despite the condition not being present. Antimicrobial resistance (AMR) is a growing global concern and the overuse of antibiotics is an important factor in increasing AMR. The ICU is an environment with high antibiotic use and improving antibiotic stewardship is a priority. Rapid biomarker-based diagnostics could achieve this by expediting the diagnostic process. In this thesis I present the findings of a multi-centre validation study of a novel bronchoalveolar lavage-based biomarker test. The diagnostic value of the measured biomarkers is discussed and the optimum biomarker-based diagnostic test for use in VAP is presented. I subsequently present a multi-centre randomised controlled trial in which the biomarker-based test is assessed in the clinical environment to determine whether it does indeed result in improved antibiotic stewardship. Trial outcomes are reported and implications are discussed.