There were no significant differences in the pharmacokinetics of micafungin and expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2) between analbuminemic and Sprague-Dawley rats. Micafungin bound strongly to high-density lipoprotein (HDL) and moderately to gamma globulin. These results suggest that HDL and gamma globulin contribute to the pharmacokinetics of micafungin.Micafungin is widely used for the treatment and prevention of various fungal infections. This antibiotic appears to be predominantly eliminated by hepatic cytochrome P450 (CYP)-mediated metabolism and partly excreted in unchanged form in the feces via hepatobiliary excretion, whereas urinary excretion is a minor excretion route (6,12,20). Moreover, it has also been reported that micafungin has no effect on the metabolism of various substrates for CYP isoforms such as CYP3A4, CYP1A2, and CYP2C9 (4,5,14,16). We have recently demonstrated that micafungin is excreted into bile mainly by multidrug resistance-associated protein 2 (ABCC2/Mrp2) and partly by ABCB1/P-glycoprotein, and its plasma protein binding level is very high (Ͼ99%) in Sprague-Dawley (SD) rats (1). The effect of plasma protein binding on the pharmacokinetics of micafungin, however, is not clear yet.Nagase analbuminemic rats, which have been established from SD rats, are characterized by a considerably low plasma albumin concentration and hyperlipidemia (13). Many studies regarding the pharmacokinetic characteristics of various drugs in Nagase analbuminemic rats have been published (2,3,(7)(8)(9)18).The present study aims to clarify the role of plasma proteins such as albumin, high-density lipoprotein (HDL), and gamma globulin in the pharmacokinetics of micafungin in analbuminemic rats.Standard solutions of micafungin and FR195743 (an internal standard) were kindly supplied by Astellas Pharma Inc. (Tokyo, Japan). Micafungin for injection was purchased commercially. Human serum albumin (HSA) was obtained from Sigma Chemicals (St. Louis, MO). Human HDL and gamma globulin were purchased from Wako Chemicals (Tokyo, Japan). C219 mouse monoclonal antibody to P-glycoprotein (Dako, Glostrup, Denmark), human monoclonal antibody against Mrp2 (Alexis Biochemicals, San Diego, CA), mouse monoclonal antibody to -actin (Sigma), and horseradish peroxidase-conjugated anti-mouse immunoglobulin G (GE Healthcare UK Ltd., Buckinghamshire, United Kingdom) were used for Western blotting. All other reagents were obtained commercially and were of the highest purity available. Micafungin, HSA, gamma globulin, and HDL were dissolved in saline.Male SD rats (8 weeks old; body weight, 270 to 295 g) and male Nagase analbuminemic rats (body weight, 225 to 250 g) of the same age as the SD rats were obtained from Japan SLC Inc. (Hamamatsu, Japan). The rats were housed under controlled environmental conditions (temperature of 23 Ϯ 1°C and humidity of 55% Ϯ 5%) with a commercial diet and water freely available. All animal experiments were carried out in accordance with the guidelines of Aichi Med...
We developed a total management system of hospital preparations to manage the preparation of raw materials, hospital preparations and the use of patient information for hospital preparations generally in Aichi Medical University Hospital and built a safe means of preparing the hospital preparations and an appropriate use regime. We used an object-relational database management system. The main functions are the management of raw materials of hospital preparations and hospital preparation stock, checking preparations and management of information of hospital preparations. In administration of hospital preparation stock, when raw materials of hospital preparations are stocked, we record in the system the batch number of raw materials for hospital preparations to secure their traceability. When the system is started up, the information of hospital preparations is shown on the display before a deadline that makes possible the administration of all hospital preparations in terms of validity in the hospital. In preparing an evaluation, we made a preparation master of hospital preparations and then raw materials of hospital preparations were authenticated and the weight checked to make it possible to prepare hospital preparations by only a pharmacist. It was effective in reducing the working hours for preparation and recording information. Moreover, the information of patient's administration ensures that informed consent is obtained where necessary and reports on clinical use results are collected. The clinical use results report recorded in the system make it possible to administer hospital preparations validly, safely, and with awareness of the side effects.
Departments of 1) Infection Control and Prevention, 2) Pharmacy, and 3) Clinical Infectious Diseases, Aichi Medical University, 4) Center for Anti-infective Research and Development, Hartford Hospital (2015 年 1 月 21 日 受付・2015 年 3 月 10 日 受理) 要 旨 Methicillin-resistant Staphylococcus aureus (MRSA)は,院内感染を引き起こす極めて重要な原因 菌である.我々は,2012 年 4 月から 2013 年 6 月までに当院で分離された新規 MRSA 検出率と消 毒量および抗菌薬使用量(AUD)について検討した.MRSA 検出率は消毒量と負の相関(r=-0.34)があり,カルバペネム系薬の AUD と正の相関(r=0.61)があった.次いで,第一世代セフ ァロスポリン(r=0.59),キノロン系薬(r=0.48)と正の相関を示した.この結果を用いて主成分分 析を行ったところ,MRSA 検出率に対する寄与率は消毒量が 20.7,カルバペネム系薬の AUD が 12.7であった.その MRSA 検出率に対する累積寄与率は,消毒量とカルバペネム系薬の AUD の総和で 86.7であった.新規解析法により,MRSA 検出率をビジュアル化することが可 能となり,MRSA 検出率の低下に繋がった. Key wordsmethicillin-resistant Staphylococcus aureus 検出率,主成分分析,消毒薬,抗菌薬使用量
Hand hygiene plays a major role in preventing infections. We analyzed the eŠect of a hand hygiene campaign for decreasing healthcare-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) at our hospital. Monthly data were retrospectively reviewed from February 2013 to March 2014. Consumption values of alcohol-based hand scrub before and after the campaign were 5.8 and 11.6 L/1000 patient-days, respectively (p<0.01). Moreover, the isolation rate of MRSA signiˆcantly decreased after the campaign from 2.5 to 1.5 (p<0.01). Aggressive hand hygiene campaigns are useful to decrease the isolation rate of HA-MRSA.
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