Translational interventions targeting the clinical use of vancomycin

Author: Cameron Phillips

Phillips, Cameron, 2020 Translational interventions targeting the clinical use of vancomycin, Flinders University, College of Medicine and Public Health

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After more than sixty years, vancomycin is still the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infection. However, vancomycin is a challenging antibiotic to prescribe and monitor as it requires individualisation of dosing and therapeutic drug monitoring. Although internationally accepted consensus-based guidelines for vancomycin dosing and monitoring are available, those recommendations have debatable impact on clinicians’ practice, as evidence shows vancomycin prescribing and monitoring is still very poor. Inappropriate dosing and monitoring of vancomycin can lead to inferior clinical outcomes, renal toxicity and the emergence of bacteria with reduced susceptibility, or resistance to the drug.

The work in this thesis aims to identify what interventions can be employed to improve vancomycin prescribing and monitoring. A theoretical framework was used to identify the barriers to improving vancomycin dosing and monitoring in our healthcare network. Domains identified were knowledge, skills, beliefs about consequences, environmental context and resources. Undertaking a systematic review and meta-analysis of interventions targeting the prescribing and monitoring of vancomycin found that multifaceted interventions are more effective than singular interventions. However, included studies were generally of short duration and poor quality. Interventional bundles comprising implementation of guidelines, providing educational meetings and the dissemination of educational materials had the greatest effect.

I conducted an initial pilot study and subsequent larger study, evaluating the effect of implementing a multifaceted intervention on vancomycin dosing and monitoring. Interventions consisted of implementing guidelines, face-to-face education, electronic continuing professional development (CPD) modules with assessment, provision of education material (pocket guideline) and dissemination of electronic communication and reminders. Post-implementation dosing, monitoring, nephrotoxicity and time-to-attainment of therapeutic target range significantly improved. Results were maintained at three-year follow-up.

The effect of face-to-face education, CPD modules and provision of pocket guidelines on junior doctors’ preparedness to use vancomycin clinically were evaluated. Attending an educational session and being in possession of a pocket guideline were associated with preparedness, measured by higher self-reported confidence to use vancomycin. High knowledge scores were achieved by pharmacists and junior doctors upon completion of a CPD module on vancomycin. Attending an educational session or being in possession of a pocket guideline did not significantly impact knowledge scores.

The determination of vancomycin minimum inhibitory concentration (MIC) can influence the decision to use vancomycin or in some cases, unnecessarily escalate therapy to a broader spectrum antibiotic. We measured the accuracy of different MIC methodology and found limited overall agreement. We established practical guidance to interpret results obtained from multiple MIC methods compared against the gold standard of broth-microdilution to inform the decision to treat with vancomycin. Further studies of these exploratory finding are required in a larger dataset.

Collectively, the work within this thesis found that a multifaceted intervention targeting healthcare professionals had a significant effect on vancomycin dosing, monitoring and safety outcomes. The multifaceted intervention studied in this work can be recommended to translate contemporary guidance on the clinical use of vancomycin to healthcare professionals, and the findings may also provide insight into implementing other antibiotic prescribing and monitoring guidelines

Keywords: anti-infective, drug monitoring, dosing, education, intervention, guideline, implementation, minimum inhibitory concentration, pharmacist, prescribing, systematic review and meta-analysis, vancomycin

Subject: Medical Science thesis

Thesis type: Doctor of Philosophy
Completed: 2020
School: College of Medicine and Public Health
Supervisor: Professor Ross McKinnon