Is there a multinational consensus of tobramycin prescribing and monitoring for cystic fibrosis? Survey of current therapeutic drug monitoring practices in USA/Canada, UK/Ireland, and Australia/New Zealand.

Abstract

Objectives: Sophisticated scientific methods have facilitated dose individualisation with substantial advancements in therapeutic drug monitoring (TDM) practice. It is unclear whether these methods have translated to the clinical setting. This study aimed to determine current TDM practice for tobramycin monitoring in cystic fibrosis (CF) centres in the USA and Canada, UK and Ireland, and Australia and New Zealand due to a high prevalence of CF.

Methods: A web-based survey was developed and circulated via CF specialist groups within the targeted geographical regions. Themes included centre demographics, tobramycin usage, dosing and infusion practices, TDM practices, and blood sampling methods.

Results: In total 77 responses were received from 75 different CF centres over the 3-month evaluation period (October 2019-January 2020). Respondents were from the USA and Canada (60%), Australia and New Zealand (25%), and the UK and Ireland (15%). Tobramycin was used in 97% of sites, with an international variation in practice across all survey aspects including dosing and infusion practice. TDM-based dose adjustment in the UK and Ireland was most commonly based only on trough sample collection for avoidance of toxicity, where use of computer programs for targeting both efficacy and toxicity endpoints were most common in Australia and New Zealand. The underlying pharmacokinetic basis of that program was not known by 33% of sites who utilised a computer program for tobramycin dose individualisation.

Conclusion: There remains substantial heterogeneity in tobramycin management worldwide. Despite two decades of research into TDM of tobramycin, there has been a slow uptake of new technologies and evolution of practice. An improved understanding of TDM processes is required for translation of evidence-based research into clinical practice. International guidelines require updating due to the advances in research to support confidence in the changes in clinical practice.