Study protocol for ADAPT-TDM: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring.

INTRODUCTION: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting. METHODS AND ANALYSIS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity. ETHICS AND DISSEMINATION: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.

Good quality of life outcomes after treatment of prosthetic joint infection with debridement and prosthesis retention.

Patients treated for early prosthetic joint infection (PJI) with surgical debridement and prosthesis retention have a rate of successful infection eradication that is similar to patients treated with the traditional approach of prosthesis exchange. It is therefore important to consider other outcomes after prosthetic joint infection treatment that may influence management decisions, such as quality of life (QOL). Our aim was to describe infection cure rates and quality of life for patients with prosthetic joint infection treated with debridement and prosthesis retention and to determine if treatment with this approach was a risk factor for poor quality of life outcomes. Prospectively collected pre and post-arthroplasty data were available for 2,134 patients, of which PJI occurred in 41. For patients treated for prosthetic joint infection, the 2-year survival free of treatment failure was 87% (95%CI 84-89). Prosthetic joint infection cases treated with debridement and retention had a similar improvement from pre-arthroplasty to 12-months post-arthroplasty as patients without PJI in QOL according to the SF-12 survey. Prosthetic joint infection treated with debridement and retention was not a risk factor for poor quality of life on univariate or multivariate analysis. Prosthetic joint infection treated with debridement and prosthesis retention results in good cure rates and quality of life. Further studies are required that directly compare quality of life for different surgical approaches for prosthetic joint infection to better inform management decisions. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:898-902, 2016.