Department of Internal medicine & Infectious Diseases, Ghent University hospital, Ghent, Belgium.
Department of Pharmacy, Ghent University hospital, Ghent, Belgium.
Acta Clin Belg. 2024 Jun;79(3):184-192. doi: 10.1080/17843286.2024.2382981. Epub 2024 Jul 26.
Flucloxacillin has the most narrow spectrum to treat staphylococcal infections, but has a large variability in bioavailability which hampers its intravenous (iv) to oral switch. To identify patients with adequate absorption, the use of an oral absorption test (OAT) measuring total plasma concentrations of flucloxacillin before and after an oral dose of 1 gram flucloxacillin, was previously published. The current pilot study aims to evaluate the fraction of patients with adequate absorption using a similar OAT; to assess the therapeutic consequences and to identify potential factors associated with adequate absorption.
Demographic data of adult patients treated with iv flucloxacillin and requiring prolonged therapy were collected retrospectively between May 2020 and November 2021 at Ghent University Hospital. A previously published OAT protocol was used, with addition of a protocol for intermittent dosing of iv flucloxacillin. Adequate absorption was defined as an increase in plasma concentration of at least 10 mg/L.
The flucloxacillin OAT was performed in 99 patients, of which 62% were men, with a median age of 58 years and 95% received intermittent dosing of iv flucloxacillin. Of the 99 patients, 55% had a result indicating an adequate absorption and 49% of all patients were switched to oral flucloxacillin afterwards. Inadequate absorption was found to be associated with higher Body Mass Index and higher flucloxacillin baseline concentration, while co-administration of acetylsalicylic acid was associated with an adequate absorption.
Based on the OAT, 49% of all patients were switched to oral flucloxacillin instead of broader-spectrum anti-staphylococcal antibiotics. This implicates that an OAT could be a valuable antimicrobial stewardship measure by restricting the use of broad-spectrum antibiotics. For each of the associations found, a hypothesis was formulated about the underlying reason or mechanism; these should be confirmed in future studies with prospective and multicentric design.
氟氯西林是治疗葡萄球菌感染的谱最窄的抗生素，但生物利用度变化很大，这阻碍了其从静脉（iv）给药到口服给药的转换。为了确定具有足够吸收能力的患者，可以使用口服吸收试验（OAT）测量 1 克氟氯西林口服剂量前后氟氯西林的总血浆浓度。之前已经发表了使用类似 OAT 来评估具有足够吸收能力的患者比例的研究；评估治疗结果并确定与足够吸收相关的潜在因素。
回顾性收集 2020 年 5 月至 2021 年 11 月期间在根特大学医院接受静脉注射氟氯西林治疗且需要长期治疗的成年患者的人口统计学数据。使用以前发表的 OAT 方案，并增加了静脉注射氟氯西林间歇性给药的方案。足够吸收定义为血浆浓度至少增加 10mg/L。
在 99 例患者中进行了氟氯西林 OAT，其中 62%为男性，中位年龄为 58 岁，95%接受了静脉注射氟氯西林的间歇性给药。在 99 例患者中，55%的结果表明吸收良好，49%的患者随后改用口服氟氯西林。吸收不足与较高的体重指数和较高的氟氯西林基线浓度相关，而同时使用乙酰水杨酸与吸收良好相关。
根据 OAT，49%的患者改用口服氟氯西林，而不是更广泛的抗葡萄球菌抗生素。这意味着 OAT 可以通过限制广谱抗生素的使用成为一种有价值的抗菌药物管理措施。对于发现的每一种关联，都提出了一个关于潜在原因或机制的假设；这些假设应在未来具有前瞻性和多中心设计的研究中得到证实。
