Exploring the opportunity for therapeutic drug monitoring (TDM) and precision dose antimicrobials in an outpatient antimicrobial therapy (OPAT) service: a prospective observational study

TL;DR

This study explores the feasibility of drug monitoring in outpatient antimicrobial therapy to improve treatment precision.

Contribution

Demonstrates the practicality of therapeutic drug monitoring in outpatient antimicrobial therapy with no on-site lab.

Findings

Drug monitoring is feasible in OPAT settings without on-site analytical capabilities.

Current dosage regimens achieved acceptable pharmacokinetic-pharmacodynamic targets.

TDM could be a viable step for precision antimicrobial therapy in outpatient care.

Abstract

Notwithstanding the wide uptake of outpatient antimicrobial therapy (OPAT) in the UK, there is a paucity of data on antimicrobial exposure. We aimed to assess antimicrobial pharmacokinetic–pharmacodynamics (PK–PD) for several agents in our service with a view to understanding a potential role for therapeutic drug monitoring (TDM) and precision antimicrobial therapy in this setting.

The study was a prospective, observational, pilot PK–PD study. Adult patients receiving intravenous ceftazidime, ceftriaxone, daptomycin, ertapenem, flucloxacillin or teicoplanin, or oral treatment with linezolid were enrolled. Peak and trough blood samples were obtained. Total and unbound antibacterial concentrations were measured. Clinical details, laboratory findings and UK OPAT good practice recommendation metrics were extracted from the medical record. PK–PD was interpreted according to EUCAST rationale documents and other published guidance. Doses were not adjusted except for linezolid and teicoplanin.

In total, 39 patients were recruited to the study, predominantly on ceftriaxone (21/39, 54%) or ertapenem (6/39, 15%). Four patients received (10%) teicoplanin, three (8%) ceftazidime, three (8%) flucloxacillin, one (3%) linezolid and one (3%) daptomycin. The most common reason for OPAT was bacteraemia and endocarditis (6/39; 15% each). PK–PD target attainment was acceptable for all drugs and dose regimens, and all β-lactam-based treatments met conservative PK–PD targets.

We have demonstrated that drug monitoring is practicable in the OPAT setting of a large institution with no on-site analytical capability. Current dosage regimens result in acceptable PK–PD target attainment. Our findings provide an initial step towards supporting TDM in OPAT.

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