Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework

• Published in: JAC-antimicrobial resistance 2024-04, Vol.6 (2), p.dlae056-dlae056
• Main Authors: Naicker, Saiyuri, Roberts, Jason A, Won, Hayoung, Wallis, Steven C, Unwin, Sean, Jamieson, Conor, Hills, Tim, Gilchrist, Mark, Santillo, Mark, Seaton, R Andrew, Drummond, Felicity, Sime, Fekade B
• Format: Article
• Language: English
• ISSN: 2632-1823; 2632-1823
• DOI: 10.1093/jacamr/dlae056

Abstract Objectives To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK’s Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice. Methods Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000 mg/1500 mg in 240 mL. The infusers were exposed to a fridge storage (2°C–8°C) for 14 days followed by 24 h in-use temperature (32°C). Results After 14 days of fridge storage and subsequent 24 h exposure to 32°C, mean ± SD of ceftazidime percent remaining was 75.5% ± 1.8%, 79.9% ± 1.1%, 82.4% ± 0.6%, for Easypump, and 81.7% ± 1.2%, 82.5% ± 0.5%, 85.4% ± 1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, mean ± SD percent remaining was 83.2% ± 1.8%, 87.4% ± 2.0%, 93.1% ± 0.9% for Easypump, and 85.1% ± 2.0%, 86.7% ± 0.1%, 92.5% ± 0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4 mg at low dose to 76.9 mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was