Nguyen Tam, Spriet Isabel, Quintens Charlotte, Vander Elst Lotte, Ha Pham Thi Thanh, Van Schepdael Ann, Adams Erwin
Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, KU Leuven, Herestraat 49, O&N2, PB 923, 3000 Leuven, Belgium.
Hospital Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
Microorganisms. 2024 Oct 9;12(10):2039. doi: 10.3390/microorganisms12102039.
Although the addition of buffers provides improved stability to flucloxacillin (FLU) solutions, unbuffered solutions are often preferred in clinical practice. The first purpose of this study was to investigate whether a 50 mg/mL solution of FLU in normal saline is stable for 24 h at 33 °C so that it can be applied for outpatient parenteral antimicrobial therapy (OPAT) using portable elastomeric infusion pumps (PEIPs). When the PEIPs were stored in an oven at 33 °C and deflated over 24 h, the volume of the collected solution, pH, and FLU concentration were checked every 4 h. Obtaining better results than expected based on the literature data, other storage conditions, such as refrigeration, room temperature (RT), 37 °C, refrigeration followed by 24 h at 33 °C and 37 °C, and different batches/brands, were also tested. This study confirmed the pronounced effect of temperature on the stability of FLU and also showed the relationship between the stability of FLU and the initial pH of the solution. FLU was quite stable at refrigeration and RT conditions, with more than 99% and 95% remaining. After 24 h at 33 °C, more than 92% of FLU was still present in the solution, while this number decreased to less than 85% when the storage temperature reached 37 °C. The remaining percentage was found to be even lower when the solution was stored at 2-8 °C for 6 days, followed by 24 h storage at 33 °C or 37 °C, with losses of 17% and 30%, respectively. The stability of FLU became worse when the initial pH of the solution was lower than 5.9 since the concentration of FLU dropped to less than 90% after 24 h at 33 °C, and a precipitate started to form when the initial pH of the solution was around 5.3. Therefore, FLU in PEIPs could be employed for 24 h if the temperature was ideally not more than 33 °C, while the pH should be not less than 5.9 upon reconstituting the FLU solution.
尽管添加缓冲剂可提高氟氯西林（FLU）溶液的稳定性，但临床实践中通常更倾向于使用未缓冲的溶液。本研究的首要目的是调查50mg/mL的FLU生理盐水溶液在33°C下能否稳定24小时，以便可使用便携式弹性输液泵（PEIP）用于门诊胃肠外抗菌治疗（OPAT）。当PEIP在33°C的烤箱中储存并在24小时内放气时，每4小时检查收集的溶液体积、pH值和FLU浓度。基于文献数据获得了比预期更好的结果，还测试了其他储存条件，如冷藏、室温（RT）、37°C、先冷藏再在33°C和37°C下储存24小时，以及不同批次/品牌。本研究证实了温度对FLU稳定性有显著影响，还显示了FLU稳定性与溶液初始pH值之间的关系。FLU在冷藏和室温条件下相当稳定，剩余量分别超过99%和95%。在33°C下放置24小时后，溶液中仍有超过92%的FLU，而当储存温度达到37°C时，这一数字降至低于85%。当溶液在2-8°C下储存6天，然后在33°C或37°C下储存24小时时，发现剩余百分比更低，损失分别为17%和30%。当溶液的初始pH值低于5.9时，FLU的稳定性变差，因为在33°C下放置24小时后FLU浓度降至低于90%，当溶液的初始pH值约为5.3时开始形成沉淀。因此，如果温度理想情况下不超过33°C，PEIP中的FLU可使用24小时，而在重新配制FLU溶液时pH值应不低于5.9。
