Pharmacy, University Hospitals Birmingham, Birmingham, UK
NHS England, Birmingham, UK.
Eur J Hosp Pharm. 2023 Dec 27;31(1):2-9. doi: 10.1136/ejhpharm-2023-003855.
Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)', which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world.
Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022.
We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.This review has not been registered under PROSPERO.
β-内酰胺类抗生素的延长输注（EI）可能会带来临床益处，与与疗效相关的关键药代动力学/药效学参数的达标概率提高相关。人们对延长和连续输注（统称为延长输注）β-内酰胺类药物以改善患者结局，特别是在重症监护病房的重症患者中，产生了浓厚的研究兴趣。虽然正在等待具有有益结果的确定性临床试验数据，但对 EI 中给予的药物的稳定性关注有限，这可能是一个同样关键的参数。由于减少了药物再配制的需求，EI 可能会节省护理时间。我们着手检查 EI 在室温下的稳定性数据，这与“稳定性推导和评估标准协议第 1 部分：无菌制备（小分子）”的要求一致，该协议允许活性药物成分（API）损失 5%，适用于使用英国药典的那些地区，也允许 API 损失 10%，适用于世界其他大部分地区。
2021 年 11 月和 2022 年 12 月，根据系统评价和荟萃分析的首选报告项目（PRISMA）原则，对室温下（23°C 或以上）延长使用的新鲜制备的β-内酰胺类抗菌药物的稳定性数据进行了搜索。
我们找到了支持扩展 12 种关键β-内酰胺类抗生素的保质期的数据，这些抗生素一旦重新配制，即可在符合 NHS 方案的情况下延长保质期（氨曲南、阿莫西林、苄青霉素、氟氯西林、哌拉西林/他唑巴坦、头孢唑林、头孢美唑、头孢卡品、头孢他啶、头孢曲松、亚胺培南和美罗培南），以及另外五种药物（替卡西林、头孢吡肟、头孢地尔、头孢西丁和多尼培南）的数据，这些药物在英国以外的地区也可以接受，超出了产品特性摘要中列出的范围。本综述未在 PROSPERO 中注册。
