Initial serum C-reactive protein level as a predictor of increasing serum vancomycin concentration during treatment

Initial serum C-reactive protein level as a predictor of increasing serum vancomycin concentration during treatment
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初始血清 C 反应蛋白水平可作为治疗期间血清万古霉素浓度增加的预测因子

DOI：
10.1097/ftd.0000000000000870
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发表时间：
2021
期刊：
TDM
影响因子：
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通讯作者：
Tsutomu Shimada; Yoshimichi Sai
Tsutomu Shimada; Yoshimichi Sai
中科院分区：
--
文献类型：
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作者：
Kazuya Isoda;Junya Nakade; Yukio Suga; Arimi Fujita;Tsutomu Shimada; Yoshimichi Sai

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背景：万古霉素治疗窗较窄，治疗期间其血药浓度-剂量比升高可引起肾毒性。因此，本研究的目的是寻找一个标记物，以确定患者的风险增加血清万古霉素在treatment.Methods：这是一个回顾性队列研究的患者万古霉素治疗的金泽大学医院，日本，从2012年4月至2015年5月。计算斯皮尔曼相关系数，以确定万古霉素浓度-剂量比变化与初始值或实验室数据和其他参数变化之间的相关性。此外，进行了多元回归分析。结果：199例患者的治疗药物监测（TDM）的静脉万古霉素治疗的2个或更多点的数据，并没有接受透析被纳入本研究。万古霉素浓度-剂量比的变化与TDM第一天的C-反应蛋白（CRP）和钠（Na）水平以及白色血细胞计数、Na和估计的肾小球滤过率（eGFR）的变化相关。多元回归分析有助于确定CRP和钠水平的TDM和eGFR的变化作为独立的影响variables.Conclusions：在TDM的第一天的血清CRP水平高是一个独立的预测增加万古霉素的浓度剂量比在接受静脉万古霉素治疗的患者，即使eGFR保持不变。背景万古霉素（VCM）用于治疗耐甲氧西林金黄色葡萄球菌感染，1，2，但它有一个狭窄的治疗指数（10-20 mg/L）。因此，血清中VCM水平的治疗药物监测（TDM）是强制性的，以最大限度地提高疗效和降低毒性，以及防止抗生素耐药性的发展。3-7由于VCM主要通过肾小球滤过消除，因此在设计VCM给药计划时必须考虑肾功能。8然而，我们观察到几个肾功能稳定的患者血清VCM浓度升高。我们医院的一个病例可以证明这一点：一名76岁的感染性心内膜炎女性接受了二尖瓣置换术，静脉注射VCM，剂量为500 mg，每日两次。第10-13天，血清VCM浓度从12.1 mg/L升高至20.0 mg/L，尽管她的病情在手术后稳定改善，但她的血清肌酐（SCr）水平保持不变（1.0-0.92 mg/dL）。最终，她在第18天发生了VCM相关肾毒性（SCr为1.53 mg/dL）。尽管已经在一些特定人群（包括肝脏疾病、肥胖和癌症患者）中研究了影响VCM药代动力学（PK）的因素9-11，但可能导致肾功能不受影响的患者中VCM PK改变的因素仍不清楚。由于在相对较短的VCM治疗期间，预计肥胖和癌症等病理因素不会发生急剧变化，因此本研究将临床实验室数据作为预测血清VCM浓度-剂量比增加的潜在标志物，旨在识别治疗期间存在万古霉素毒性风险的患者。除了现有的生物标志物（如SCr）外，确定影响血清VCM浓度的新因素将有助于优化VCM个体化给药方案。因此，本研究的目的是通过研究万古霉素治疗期间血清浓度升高的关系，找到一个预测患者在治疗期间血清万古霉素浓度升高风险的标志物。
Background:Vancomycin has a narrow therapeutic window, and an increase in its serum concentration-to-dose ratio during treatment can cause renal toxicity. Therefore, this study was aimed at finding a marker to identify patients at risk of increasing serum vancomycin during treatment.Methods:This was a retrospective cohort study of patients treated with vancomycin at Kanazawa University Hospital, Japan, from April 2012 to May 2015. Spearman correlation coefficients were calculated to determine the correlations between changes in vancomycin concentration-to-dose ratio and initial values or changes in laboratory data and other parameters. In addition, a multiple regression analysis was conducted.Results:One hundred ninety-nine patients for whom 2 or more points of data on therapeutic drug monitoring (TDM) of intravenous vancomycin treatment were available and did not undergo dialysis were included in the study. Changes in vancomycin concentration-to-dose ratio were associated with C-reactive protein (CRP) and sodium (Na) levels on the initial day of TDM and with changes in white blood cell count, Na, and estimated glomerular filtration rates (eGFRs). Multiple regression analysis helped identify CRP and Na levels on the initial day of TDM and change in eGFR as independent influencing variables.Conclusions:A high serum CRP level on the initial day of TDM is an independent predictor of increasing vancomycin concentration-to-dose ratio in patients receiving intravenous vancomycin treatment, even if eGFR remains unchanged.BACKGROUNDVancomycin (VCM) is used to treat methicillin-resistant Staphylococcus aureus infection, 1, 2 but it has a narrow therapeutic index (10–20 mg/L). Therefore, therapeutic drug monitoring (TDM) of VCM levels in serum is mandatory to maximize efficacy and minimize toxicity, as well as to prevent the development of antimicrobial resistance. 3–7 Because VCM is primarily eliminated through glomerular filtration, it is essential to consider renal function when designing a VCM dosing plan. 8 However, we observed elevation in serum VCM concentrations in several patients with stable renal function. This can be exemplified by a case in our hospital: a 76-year-old woman with infective endocarditis received mitral valve replacement, and intravenous VCM was initiated at a dose of 500 mg twice daily. The serum VCM concentrations increased from 12.1 to 20.0 mg/L on day 10–13, although her condition improved steadily after the operation, and her serum creatinine (SCr) level remained unchanged (1.0–0.92 mg/dL). Eventually, she developed VCM-associated nephrotoxicity on day 18 (SCr was 1.53 mg/dL). Although the factors influencing VCM pharmacokinetics (PK) have been studied in some specific populations, including patients with hepatic disorder, obesity, and cancer, 9–11 the factors that may cause altered VCM PK in patients with unaffected kidney function remain unclear. Because pathological factors such as obesity and cancer are not expected to change drastically during the relatively short periods of VCM treatment, this study focused on clinical laboratory data as potential markers for predicting an increase in serum VCM concentration-to-dose ratios, with the aim of identifying patients at risk for vancomycin toxicity during treatment. The identification of new factors influencing serum VCM concentrations, in addition to existing biomarkers such as SCr, would be helpful for optimizing individualized VCM dosing schedules. Therefore, the aim of this study was to find a marker to predict patients at risk of increasing serum vancomycin concentrations during treatment, by investigating the relationship …