Higashi Mika, Nakano Takafumi, Sato Keisuke, Eguchi Yukiomi, Moriwaki Norihiro, Kamada Mitsuhiro, Ikeuchi Tadahiro, Kaneshige Susumu, Uchiyama Masanobu, Hayashi Toshinobu, Togawa Atsushi, Matsuo Koichi, Kamimura Hidetoshi
Department of Pharmacy, Fukuoka University Hospital, Jonan-ku, Fukuoka 814-0133, Japan.
Department of Oncology and Infectious Disease Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University, Jonan-ku, Fukuoka 814-0180, Japan.
J Clin Med Res. 2024 Aug;16(7-8):325-334. doi: 10.14740/jocmr5238. Epub 2024 Aug 10.
Vancomycin regimens are designed to achieve an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio ranging between 400 and 600 µg·h/mL in the steady state. However, in cases of critical infections such as bacteremia requiring an early treatment approach, the clinical course may be affected by the AUC/MIC before reaching the steady state, that is, the AUC/MIC values 24 h after the first dose (first 24-h AUC/MIC). This study evaluated the relationship between the first 24-h AUC/MIC and the clinical course of methicillin-resistant (MRSA) infection.
We retrospectively reviewed the records of patients with MRSA bacteremia in a university hospital between 2015 and 2022. The first 24-h AUC/MIC cutoff was set at 300 µg·h/mL based on the results of early response, and eligible patients were divided into groups with a first 24-h AUC/MIC either < 300 µg·h/mL (< 300 group, n = 32) or ≥ 300 µg·h/mL (≥ 300 group, n = 38). The primary endpoint was the rate of treatment efficacy, and the secondary endpoints were time to clinical and bacteriological improvement and 30-day survival rate.
Treatment efficacy and 30-day survival rates were not significantly different between the two groups (78.1% vs. 79.0%, P = 0.933 and 83.9% vs. 87.2%, P = 0.674, respectively). Among patients who showed treatment efficacy, the median time to clinical and bacteriological improvement was 11.5 days and 8.0 days in the < 300 and ≥ 300 groups, respectively; compared to the ≥ 300 group, the < 300 group had a significantly longer time to improvement (P = 0.001).
The first 24-h AUC/MIC had no effect on the treatment efficacy and 30-day survival rates. However, the time to clinical and bacteriological improvement was significantly prolonged in the < 300 group, indicating that the first 24-h AUC/MIC does not affect the rate of therapeutic efficacy but may affect the treatment period.
万古霉素治疗方案旨在使稳态下浓度-时间曲线下面积/最低抑菌浓度（AUC/MIC）比值在400至600µg·h/mL之间。然而，在诸如菌血症等需要早期治疗的严重感染病例中，临床病程可能在达到稳态之前就受到AUC/MIC的影响，即首剂给药后24小时的AUC/MIC值（首剂24小时AUC/MIC）。本研究评估了首剂24小时AUC/MIC与耐甲氧西林金黄色葡萄球菌（MRSA）感染临床病程之间的关系。
我们回顾性分析了2015年至2022年期间某大学医院MRSA菌血症患者的病历。根据早期反应结果，将首剂24小时AUC/MIC临界值设定为300µg·h/mL，符合条件的患者被分为首剂24小时AUC/MIC＜300µg·h/mL（＜300组，n = 32）或≥300µg·h/mL（≥300组，n = 38）两组。主要终点是治疗有效率，次要终点是临床和细菌学改善时间以及30天生存率。
两组之间的治疗有效率和30天生存率无显著差异（分别为78.1%对79.0%，P = 0.933；83.9%对87.2%，P = 0.674）。在显示治疗有效的患者中，＜300组和≥300组临床和细菌学改善的中位时间分别为11.5天和8.0天；与≥300组相比，＜300组的改善时间明显更长（P = 0.001）。
首剂24小时AUC/MIC对治疗有效率和30天生存率没有影响。然而，＜300组的临床和细菌学改善时间显著延长，这表明首剂24小时AUC/MIC不影响治疗有效率，但可能影响治疗周期。
