Saiyuri Naicker, Jason A Roberts, Hayoung Won, Steven C Wallis, Sean Unwin, Conor Jamieson, Tim Hills, Mark Gilchrist, Mark Santillo, R Andrew Seaton, Felicity Drummond, Fekade B Sime
{"title":"利用国家稳定性协议框架,评估用于门诊非肠道抗菌治疗的弹性输注装置中头孢他啶/阿维菌素的稳定性。","authors":"Saiyuri Naicker, Jason A Roberts, Hayoung Won, Steven C Wallis, Sean Unwin, Conor Jamieson, Tim Hills, Mark Gilchrist, Mark Santillo, R Andrew Seaton, Felicity Drummond, Fekade B Sime","doi":"10.1093/jacamr/dlae056","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure.</p><p><strong>Conclusions: </strong>Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.</p>","PeriodicalId":14594,"journal":{"name":"JAC-Antimicrobial Resistance","volume":"6 2","pages":"dlae056"},"PeriodicalIF":3.7000,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995722/pdf/","citationCount":"0","resultStr":"{\"title\":\"Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.\",\"authors\":\"Saiyuri Naicker, Jason A Roberts, Hayoung Won, Steven C Wallis, Sean Unwin, Conor Jamieson, Tim Hills, Mark Gilchrist, Mark Santillo, R Andrew Seaton, Felicity Drummond, Fekade B Sime\",\"doi\":\"10.1093/jacamr/dlae056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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 <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure.</p><p><strong>Conclusions: </strong>Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.</p>\",\"PeriodicalId\":14594,\"journal\":{\"name\":\"JAC-Antimicrobial Resistance\",\"volume\":\"6 2\",\"pages\":\"dlae056\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-04-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10995722/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAC-Antimicrobial Resistance\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/jacamr/dlae056\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/4/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAC-Antimicrobial Resistance","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jacamr/dlae056","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/4/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Evaluation of the stability of ceftazidime/avibactam in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy utilizing a national stability protocol framework.
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 <10% for at least 12 h of the running phase, if stored in a fridge for not more than 72 h prior to in-use temperature exposure.
Conclusions: Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12 hourly infusion in those territories where degradation of ≤10% is deemed acceptable.