门诊患者肠外抗菌治疗中替莫西林的稳定性：这是一个可行的选择吗？

Stability of temocillin in outpatient parenteral antimicrobial therapy: is it a real option?

机构信息

Unidad de Gestión Clínica de Farmacia, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.

Unidad de Gestión Clinica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío/Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain.

出版信息

J Antimicrob Chemother. 2023 Oct 3;78(10):2451-2456. doi: 10.1093/jac/dkad251.

DOI:10.1093/jac/dkad251

PMID:37574704

Abstract

BACKGROUND

Temocillin is an interesting alternative to carbapenems for susceptible Enterobacteriaceae. Although its use in outpatient parenteral antimicrobial therapy (OPAT) programmes has generated interest, this has been hampered by the lack of stability data.

OBJECTIVES

The purpose of the present study was to evaluate the physical and chemical stability of temocillin at the recommended dose for its use in OPAT programmes, contained in polypropylene infusion bags or polyisoprene elastomeric devices at different temperatures, and to describe a novel LC-MS/MS developed for the quantification of temocillin.

METHODS

Temocillin daily dose (6 g) was diluted in 500 mL of 0.9% sodium chloride to obtain a final concentration of 12 g/L. This solution was stored at 4°C, 25°C, 32°C and 37°C for 72 h, both in polypropylene infusion bags and in polyisoprene elastomeric pumps. Physical and chemical stability were evaluated during 72 h after manufacturing. Solutions were considered stable if colour, clearness and pH remained unchanged and if the percentage of intact drug was ≥90%.

RESULTS

Temocillin attained the chemical stability criterion of ≥90% of the original concentration for the whole experiment in both devices at 4°C, 25°C and 32°C. At 37°C, temocillin was stable for 24 h but its concentration dropped below 90% from that timepoint. No precipitation occurred and minor colour changes were observed.

CONCLUSIONS

Temocillin is stable under OPAT conditions and it would be an appropriate candidate for the treatment of patients who can be discharged to complete therapy in an OPAT programme. For this study, an LC-MS/MS method was developed.

摘要

背景

替莫西林是一种替代敏感肠杆菌科碳青霉烯类药物的有趣选择。尽管其在门诊患者的肠外抗菌治疗（OPAT）方案中的应用引起了关注，但由于缺乏稳定性数据，这一应用受到了阻碍。

目的

本研究的目的是评估替莫西林在 OPAT 方案中推荐剂量下的物理和化学稳定性，该剂量在不同温度下分别装在聚丙烯输液袋或聚异戊二烯弹性体装置中，并描述一种新开发的用于替莫西林定量的 LC-MS/MS 方法。

方法

将替莫西林的每日剂量（6 g）稀释至 500 mL 0.9%氯化钠中，以获得最终浓度为 12 g/L。该溶液在 4°C、25°C、32°C 和 37°C 下储存 72 h，分别在聚丙烯输液袋和聚异戊二烯弹性体泵中储存。在生产后 72 h 内评估物理和化学稳定性。如果颜色、透明度和 pH 值保持不变，且药物的完整百分比≥90%，则认为溶液稳定。