Loeuille Guillaume, D'Huart Elise, Vigneron Jean, Nisse Yann-Eric, Beiler Benoit, Polo Caroline, Ayari Gillian, Sacrez Matthieu, Demoré Béatrice, Charmillon Alexandre
Pharmacy Department, University Hospital, 54511 Vandoeuvre-lès-Nancy, France.
Infostab, Non-Profit Association, 54180 Heillecourt, France.
Antibiotics (Basel). 2022 Mar 29;11(4):458. doi: 10.3390/antibiotics11040458.
The use of continuous infusion to improve the therapeutic efficacy of time-dependent antibiotics has been demonstrated. There is still a lack of data to safely perform these continuous infusions. The objectives in this study were to evaluate the stability by using stability-indicating methods (High-Performance Liquid Chromatography) of 16 antibiotics in concentrated solutions, especially for administration in intensive care units and solutions in elastomeric diffusers at 37 °C for outpatient parenteral antimicrobial therapy. The solutions were considered stable if the percentage of the drug was ≥90%, and the colour and clearness remained unchanged. In syringes, the stability data vary from 4 to 8 h (h) for meropenem in Dextrose 5% (D5W) and Normal Saline (NS), respectively, 6 h for cefotaxime, 12 h for cefoxitin, and 24 h for aztreonam, cefazolin, cefepime, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam in NS and D5W, and in water for injection for cloxacillin. A stability period of 48 h has been validated for vancomycin (D5W), aztreonam, and piperacillin/tazobactam. Cefoxitin, cefazolin, cefepime, cefotaxime, cloxacillin, and piperacillin are unstable for diffuser administration. In diffusers, stability times vary from 6 h for cefiderocol, 8 h for ceftazidime, 12 h for ceftazidime/avibactam and ceftolozane/tazobactam (NS), 24 h for temocillin (NS) and piperacillin/tazobactam (D5W), up to 48 h for aztreonam and vancomycin. Solutions stored at 37 °C are less stable and allow the administration of seven antibiotics using diffusers.
持续输注以提高时间依赖性抗生素的治疗效果已得到证实。目前仍缺乏安全进行这些持续输注的数据。本研究的目的是使用稳定性指示方法(高效液相色谱法)评估16种抗生素在浓缩溶液中的稳定性,特别是用于重症监护病房给药以及在37℃下用于门诊胃肠外抗菌治疗的弹性体扩散器中的溶液。如果药物百分比≥90%且颜色和澄清度保持不变,则认为溶液稳定。在注射器中,美罗培南在5%葡萄糖(D5W)和生理盐水(NS)中的稳定性数据分别为4至8小时,头孢噻肟为6小时,头孢西丁为12小时,氨曲南、头孢唑林、头孢吡肟、头孢地尔、头孢他啶/阿维巴坦、头孢托罗/他唑巴坦在NS和D5W以及注射用水中用于氯唑西林时为24小时。万古霉素(D5W)、氨曲南和哌拉西林/他唑巴坦的稳定期已验证为48小时。头孢西丁、头孢唑林、头孢吡肟、头孢噻肟、氯唑西林和哌拉西林用于扩散器给药时不稳定。在扩散器中,稳定性时间从头孢地尔的6小时、头孢他啶的8小时、头孢他啶/阿维巴坦和头孢托罗/他唑巴坦(NS)的12小时、替莫西林(NS)和哌拉西林/他唑巴坦(D5W)的24小时到氨曲南和万古霉素的48小时不等。在37℃下储存的溶液稳定性较差,使用扩散器可用于七种抗生素的给药。