Systematic review of the stability of antimicrobial agents in elastomeric devices for outpatient parenteral antimicrobial therapy services based on NHS Yellow Cover Document standards.

Abstract

Background: In order to use aseptically prepared elastomeric infusers, outpatient parenteral antimicrobial therapy (OPAT) services require extended stability data for antimicrobial agents to assign a product shelf-life. In the UK, the relevant standards for stability testing and shelf-life assignment are published in 'A Standard Protocol for Deriving and Assessment of Stability-Part 1 (Aseptic Preparations-Small Molecules), commonly called the Yellow Covered Document (YCD). A previous systematic review published in 2017 failed to identify data on the stability of antimicrobials in elastomeric devices for OPAT services that met YCD requirements in force at the time. The aim of this review was to update that search, following a subsequent change to YCD requirements in 2017 and 2019 and expand that dataset to identify progress made in providing assurance about the stability of antimicrobial agents for OPAT services.

Methods: Searches were undertaken for papers relating to extended stability of antimicrobials. Citations were included when antimicrobial shelf-life was assessed using a stability-indicating method and considered a period of storage, either refrigerated or at room temperature, followed by in-use testing at a temperature at or above 32°C.

Results: Of 267 initial citations, six met the inclusion criteria and underwent full text review for data extraction. Included antimicrobials were cefazolin, ceftazidime, piperacillin/tazobactam, flucloxacillin and ceftolozane/tazobactam. Of these, only flucloxacillin and piperacillin demonstrated YCD compliant stability over the 24-hour infusion period while cefazolin, ceftazidime and ceftolozane/tazobactam could be infused over 12-hour period.

Conclusions: Contrary to the position found in 2017 review, high-quality data are now available to support the use of a number of antimicrobial agents in extended infusion in elastomeric devices for OPAT services. There is a need to expand the dataset, as well as developing international consensus on the ideal parameters for stability assessment of such infusions in elastomeric devices.