Jamieson Conor, Drummond Felicity, Hills Tim, Ozolina Laima, Gilchrist Mark, Seaton R Andrew, Santillo Mark, Wilkinson Alan-Shaun, Allwood Michael C
Pharmacy Department, Sandwell and West Birmingham NHS Trust, Birmingham, UK.
British Society for Antimicrobial Chemotherapy (BSAC), Birmingham, UK.
JAC Antimicrob Resist. 2021 Sep 27;3(3):dlab141. doi: 10.1093/jacamr/dlab141. eCollection 2021 Sep.
To investigate the stability of ceftolozane/tazobactam 5 mg/mL and 20 mg/mL solutions for infusion in two elastomeric devices: FOLFusor LV10 (Baxter Healthcare) and Easypump II (B. Braun Medical Ltd) and determine if an extended shelf life of up to 8 days storage at 2-8°C plus 24 h 'in use' at 32°C was achievable.
Testing was as per the latest NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A stability-indicating LC method was used for assessing the stability of solutions of ceftolozane/tazobactam at 5 mg/mL and 20 mg/mL (combined concentration of both actives) respectively, tested in two batches in triplicate (3) at five timepoints according to the requirements of the YCD.
Ceftolozane/tazobactam, diluted in 0.9% w/v sodium chloride at 5 mg/mL and 20 mg/mL, degraded during in-use storage at 32°C with <95% remaining after 18 h for some device/concentration combinations and all device/concentration combinations at 24 h, respectively. The data does support extended storage of up to 8 days at 2-8°C plus 12 h at 32°C 'in-use' when using either FOLFusor LV10 or Easypump II devices and is compliant with YCD.
Solutions of ceftolozane/tazobactam can be administered in outpatient parenteral antimicrobial therapy (OPAT) services following refrigerated storage for up to 8 days, when limited to a 12 h infusion at in-use temperature of 32°C. For UK OPAT services where twice daily dosing is feasible, our data provides another treatment option for challenging infections. In countries where a 10% loss of ceftolozane/tazobactam is acceptable, a 24 h infusion is supported by the data.
研究头孢洛扎/他唑巴坦5mg/mL和20mg/mL输注溶液在两种弹性输液装置（FOLFusor LV10，百特医疗公司；Easypump II，贝朗医疗有限公司）中的稳定性，并确定在2-8°C下最多储存8天加上在32°C下“使用中”24小时的延长保质期是否可行。
按照英国国家医疗服务体系（NHS）药品质量保证委员会黄色封面文件（YCD）的最新要求进行测试。采用一种稳定性指示液相色谱法，分别评估5mg/mL和20mg/mL（两种活性成分的总浓度）头孢洛扎/他唑巴坦溶液的稳定性，根据YCD的要求，分两批进行测试，每个批次重复三次，在五个时间点进行检测。
以5mg/mL和20mg/mL稀释于0.9%w/v氯化钠中的头孢洛扎/他唑巴坦，在32°C使用过程中储存时会降解，对于某些装置/浓度组合，18小时后剩余量<95%，而在24小时时，所有装置/浓度组合的剩余量均<95%。数据确实支持使用FOLFusor LV10或Easypump II装置时，在2-8°C下最多储存8天加上在32°C“使用中”12小时的延长储存时间，并且符合YCD要求。
头孢洛扎/他唑巴坦溶液在冷藏储存长达8天后，可用于门诊肠外抗菌治疗（OPAT）服务，但在使用温度32°C下的输注时间限制为12小时。对于英国可行每日两次给药的OPAT服务，我们的数据为治疗难治性感染提供了另一种治疗选择。在头孢洛扎/他唑巴坦损失10%可接受的国家，数据支持24小时输注。
