Division of Pharmacy, School of Medicine, 3925University of Tasmania, Australia.
School of Healthcare, University of Leeds, UK.
Perit Dial Int. 2020 Sep;40(5):470-476. doi: 10.1177/0896860820902590. Epub 2020 Feb 13.
Peritonitis is a common and serious complication of peritoneal dialysis (PD). PD-associated peritonitis (PDAP) caused by is usually resistant to most antibiotics, resulting in high failure rates. Ceftolozane/tazobactam (C/T) has been shown to be effective in treating urinary tract and intra-abdominal infections caused by beta-lactam resistant and other gram-negative bacteria. Given its favourable adverse effects profile, it has a potential role in the treatment of PDAP caused by species resistant to other antibiotics. Intraperitoneal administration of antibiotics admixed with PD solutions for the treatment of PDAP is associated with superior outcomes. However, there is a lack of published data on the stability of C/T in PD solutions. Therefore, this study investigated the physical and chemical stability of C/T in commonly used PD solutions at different temperatures.
A total of 27 PD bags (3 PD bags for each type of PD solution including Dianeal®, Extraneal®, Balance® and Physioneal® PD bags) containing C/T were prepared and stored at 25°C for 6 h, followed by 4°C for 168 h and then 37°C for 12 h. An aliquot from each PD bag was withdrawn, and the concentration of C/T before (0 h) and after predefined time points was determined using a stability-indicating high-performance liquid chromatography assay. Samples were also assessed for pH, colour change and particulate matter immediately after preparation and on each day of analysis.
C/T retained more than 97% of their initial concentration when stored at 25°C for 6 h followed by storage at 4°C for 168 h and then at 37°C for 12 h. Particle formation was not detected at any time under the tested storage conditions. The pH and colour remained essentially unchanged throughout the study.
These results provide a platform for clinical studies to determine the safety and therapeutic efficacy of intraperitoneal C/T for the treatment of PDAP caused by resistant species.
腹膜炎是腹膜透析（PD）的常见且严重的并发症。由 引起的 PD 相关性腹膜炎（PDAP）通常对大多数抗生素具有耐药性，导致治疗失败率较高。头孢他唑巴坦/他唑巴坦（C/T）已被证明对由β-内酰胺耐药的 和其他革兰氏阴性菌引起的尿路感染和腹腔内感染有效。鉴于其有利的不良影响特征，它在治疗对其他抗生素耐药的 引起的 PDAP 方面具有潜在作用。混合 PD 溶液的腹腔内给予抗生素治疗 PDAP 与更好的结果相关。然而，关于 C/T 在 PD 溶液中的稳定性，目前尚无发表的数据。因此，本研究在不同温度下研究了 C/T 在常用 PD 溶液中的物理和化学稳定性。
共制备了 27 袋 PD（每种 PD 溶液 3 袋，包括 Dianeal®、Extraneal®、Balance®和 Physioneal®PD 袋），C/T 包含在其中，并在 25°C 下储存 6 小时，然后在 4°C 下储存 168 小时，再在 37°C 下储存 12 小时。从每个 PD 袋中取出一份样品，使用指示稳定性的高效液相色谱法测定 C/T 在预定时间点之前（0 小时）和之后的浓度。在制备后和分析的每一天，立即评估样品的 pH 值、颜色变化和颗粒物质。
C/T 在 25°C 下储存 6 小时后再在 4°C 下储存 168 小时，然后在 37°C 下储存 12 小时，其初始浓度保留超过 97%。在测试的储存条件下，任何时候都未检测到颗粒形成。在整个研究过程中，pH 值和颜色基本保持不变。
这些结果为临床研究提供了一个平台，以确定腹腔内 C/T 治疗耐药 引起的 PDAP 的安全性和治疗效果。
