Rentsch Katharina M, Khanna Nina, Halbeisen Delia, Osthoff Michael
Department of Laboratory Medicine, University Hospital Basel, 4031 Basel, Switzerland.
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, 4031 Basel, Switzerland.
Antibiotics (Basel). 2024 Oct 14;13(10):970. doi: 10.3390/antibiotics13100970.
: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use of benzylpenicillin in OPAT requires special consideration because of its limited stability at elevated temperatures. : We tested the benzylpenicillin stability, pH, and degradation of products in elastomeric pumps at different concentrations in saline and in buffered solution containing sodium citrate during a prolonged storage and at high temperatures (seven days at 2-8 °C followed by 24 h at 37 °C). Additionally, drug concentrations during intermittent bolus infusion and during OPAT were determined in five patients. The concentrations and degradation products of benzylpenicillin were measured using liquid chromatography mass spectrometry (LC-MS/MS). : Unbuffered benzylpenicillin solutions that were already degraded during refrigerator storage and analyte concentration were not measurable after 8 days. The stability of the buffered solutions was acceptable at all three of the tested concentrations (97.6 ± 1.3%, 96.3 ± 0.8%, and 94.9 ± 1.1% for 10 Mio IU, 20 Mio IU, and 40 Mio IU of benzylpenicillin). The stability was influenced by benzylpenicillin concentration, and several breakdown products were identified. Benzylpenicillin concentrations were measured in five patients during OPAT and ranged from 7.2 to 60 mg/L. : Benzylpenicillin buffered with sodium citrate is a safe and convenient option for use in continuous infusions during OPAT and should be favored over broad-spectrum antibiotics. Therapeutic drug monitoring data indicate sufficient to high plasma levels when patients received benzylpenicillin as continuous infusions.
窄谱β-内酰胺类抗生素，如苄青霉素和氟氯西林，越来越多地用于门诊胃肠外抗菌治疗（OPAT）项目中，以减轻与广谱抗生素相关的不良反应。在OPAT期间，这些β-内酰胺类药物需要通过便携式输液设备持续给药。然而，由于苄青霉素在高温下稳定性有限，在OPAT中使用时需要特别考虑。：我们测试了在长时间储存和高温（2-8°C下7天，然后在37°C下24小时）条件下，弹性泵中不同浓度的苄青霉素在生理盐水和含柠檬酸钠的缓冲溶液中的稳定性、pH值和产物降解情况。此外，还测定了5例患者在间歇推注输液和OPAT期间的药物浓度。使用液相色谱质谱联用仪（LC-MS/MS）测量苄青霉素的浓度和降解产物。：未缓冲的苄青霉素溶液在冷藏储存和分析物浓缩过程中已经降解，8天后无法测量。在所有三个测试浓度下，缓冲溶液的稳定性都是可以接受的（1000万IU、2000万IU和4000万IU苄青霉素的稳定性分别为97.6±1.3%、96.3±0.8%和94.9±1.1%）。稳定性受苄青霉素浓度影响，并鉴定出几种分解产物。在OPAT期间对5例患者的苄青霉素浓度进行了测量，范围为7.2至60mg/L。：用柠檬酸钠缓冲的苄青霉素是OPAT期间连续输注的一种安全方便的选择，应优先于广谱抗生素使用。治疗药物监测数据表明，当患者接受苄青霉素连续输注时，血浆水平足以达到高浓度。
