目的:分析恶性血液病儿童患者中泊沙康唑血浆谷浓度(trough concentration,Cmin)数据,并探讨影响Cmin的因素,为泊沙康唑个体化用药提供参考.方法:回顾性收集广州市第一人民医院2021年3月至2023年1月开展泊沙康唑治疗药物监测的恶性血液病儿童患者临床资料,分析年龄、性别、体质量、腹泻、合并用药等因素对泊沙康唑Cmin的影响.结果:共纳入符合标准的儿童患者39例,收集130例次Cmin监测数据,其中70例次的泊沙康唑Cmin＞0.7mg·L-1,达标率为53.8％.患者体质量、给药剂量、合用质子泵抑制剂、特殊病理状态(腹泻、呕吐和肝功能)与泊沙康唑Cmin显著相关.结论:影响恶性血液病儿童患者泊沙康唑Cmin的因素较多,需密切进行治疗药物监测,且需根据体质量、合并质子泵抑制剂及特殊病理状态调整泊沙康唑给药方案,以确保应用泊沙康唑的有效性和安全性.

BACKGROUND:Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT. METHODS:This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety. DISCUSSION:This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT. TRIAL REGISTRATION:Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .

目的 通过分析某院0～6岁患者万古霉素血药浓度达标率及用药剂量的关系,探讨优化儿童患者万古霉素给药方案.方法 根据纠正胎龄后的年龄将患儿分为A(年龄＜7 d),B(年龄7～28 d),C(年龄＞28 d)3组,分析不同年龄组患儿万古霉素血药浓度水平和达标率情况,比较说明书推荐剂量、指南推荐剂量与实际剂量的差别.结果 106例0～6岁患儿监测万古霉素血药浓度168例次,以5～15 mg·L-1为目标谷浓度的万古霉素达标率为57.74％(98/168).A、B、C 3组的血药浓度达标率分别为43.59％(17/39),54.00％(27/50)和67.09％(53/79),A、B 组达标率低于 C 组,差异有统计学意义(P＜0.05).A、B、C 3组的平均血药浓度分别为(15.88±1.36),(13.51±0.82)和(11.10±0.69),C组的平均血药浓度低于另外2组,差异有统计学意义(P＜0.05).A组浓度达标患者的实际用量高于指南推荐剂量,差异有统计学意义(P＜0.05),与说明书推荐的最大剂量差异无统计学意义(P＞0.05).B组浓度达标患者的实际用量高于说明书及指南推荐剂量,差异均有统计学意义(P＜0.05).C组浓度达标患者的实际用量高于说明书推荐剂量,差异有统计学意义(P＜0.05),与指南推荐剂量差异无统计学意义(P＞0.05).结论 该院0～6岁患儿万古霉素血药浓度达标率整体偏低,尤其是新生儿.对于肾功能正常的儿童,日龄7 d以内的患儿初始剂量可以按照说明书用药,日龄大于7 d的患儿可用稍大于说明书推荐的最大剂量,说明书推荐1月以上患儿的用药剂量偏小,应按照指南每天至少给予60 mg·kg-1的初始剂量.

肺炎克雷伯菌致脓性肝脓肿(KP-PLA)是一种严重威胁生命的疾病[1],自1986年文献首次报道了高毒力肺炎克雷伯菌(hypervirulent Klebsiella pneumoniae,hvKP)引起多部位脓肿的病例后2],关于hvKP转移性或侵袭性的感染报道逐渐增加[3].目前多数文献为hvKP致肝脓肿的流行病学[4-5]、毒力基因[6]等研究,对KP-PLA的治疗可见于一些病例报告,而结合血药浓度监测的KP-PLA治疗尚无报道.本文通过介绍1例肝脓肿并发脑脓肿的患者,结合抗菌药物血药浓度监测情况,对患者抗感染治疗过程中抗菌药物使用情况进行分析和评价,为KP-PLA患者提供抗感染治疗方案的建议,为个体化治疗提供依据.

目的 了解某三级甲等医院永久性心脏起搏器植入术患者围术期预防用抗菌药物使用现状及存在问题,促进临床合理使用抗菌药物.方法 对该院2018～2020年161例永久性心脏起搏器植入术患者的病历资料进行回顾性调查分析.结果 161例永久性心脏起搏器植入术患者全部预防性使用抗菌药物,使用率100％;抗菌药物选择涉及6个类别共9个品种,合理率为90.1％;给药剂量合理率96.3％;给药频次合理率为78.9％;给药时机合理率为98.8％;给药途径均为静脉滴注,合理率100％;预防用药疗程为4.3～8.0 d,平均疗程为5.8d,疗程合理率为3.7％;无联合用药情况.结论 该院永久性心脏起搏器植入术预防使用抗菌药物存在的主要问题为用药疗程偏长、部分药物给药频次不适宜及部分过敏患者选药不适宜,医院管理部门应加大管理力度,临床药师应加强干预和用药教育,不断提高临床合理用药水平.

目的 通过对万古霉素引起儿童不良反应的文献进行统计和分析,探讨其不良反应发生的特点和原因,为儿童合理用药提供依据.方法 以"万古霉素"、"不良反应"等主要检索词,检索中国期刊全文数据库(CNKI)、万方数据库、维普医学网的文献资料,依据纳排标准对文献进行筛选,将纳入的文献病例资料进行归纳与分析,统计不同血药浓度的不良反应发生率.结果 检索建库以来至2019年10月,共筛选纳入文献7篇,总例数为946例,其中未达到10mg·L-1为715例(占75.58％),大于10mg·L-1为231例(占24.42％).按患儿血药浓度范围、总例数、肝功能损害例数、肾功能损害例数、听力损害例数以10mg·L-1为界限进行归纳与分析,超过10mg·L-1肝功能损害、肾功能损害发生率增加;而在听力损害中无统计学差异.结论 万古霉素的谷浓度大于10mg·L-1时,肝肾功能的损害明显增加,需及时监测其血药浓度,以保障用药安全性.

目的 建立HPLC法测定人血中伏立康唑浓度的方法,并应用于患者的个体化治疗.方法 以Agilent technologies ZORBAX SB-C18(150×4.6mm,5μm)色谱柱分离,柱温30℃,流动相为甲醇:水=53:47,流速1.0mL·min-1,检测波长为256nm,进样量为30μL,卡马西平为内标.结果 伏立康唑浓度在0.31～19.84μg·mL-1范围内,呈良好的线性关系,最低检测限0.31μg·mL-1(S/N≥10).结论 本方法快速、简便、稳定,适合用于伏立康唑血药浓度的测定.伏立康唑血药浓度个体差异大,开展治疗药物监测有利于保证患者安全、有效用药.

目的:探讨伏立康唑引起神经系统药品不良反应（ADRs）的特征,为临床合理用药提供参考。方法:对一例伏立康唑引起癫■发作及精神障碍病例的临床表现、高危因素进行分析,并结合相关文献分析其发生机制及防治措施。结果:癫■发作是伏立康唑少见的神经系统ADRs,本例患者伏立康唑血药浓度过高是引发神经系统ADRs的主要原因。结论:临床使用伏立康唑应进行血药浓度监测,实行个体化用药,避免因血药浓度过高引起神经系统ADRs。

OBJECTIVE To optimize the anti-infection regimen of meropenem in CRRT patients by Monte Carlo Simulation (MCS). METHODS The parameters of PK/PD of meropenem were retrieved through literature, and Crystal Ball software was used to simulate the target rate of meropenem with different dosage regimens for the treatment of pseudomonas aeruginosa infection at different CRRT dosages, and to analyze and summarize the best regimen. RESULTS The clearance rate of meropenem was higher in CVVH than in CVVHD. With the increase of CRRT dosage, the clearance rate of meropenem increased. When the MIC of pseudomonas aeruginosa was set at 2 mg·L-1, the f％T>4×MIC of meropenem treatment schemes could reach more than 40％. When the total daily dose was the same, the pharmacodynamic index of 500 mg q6 h was better than 1 000 mg q12 h, the f％ T> 4 × MIC of the first dosage doubling scheme increased, but all schemes could reach 40％, it could not show the advantage of the loading dosage. When the MIC was4 mg·L-1, the f％T>4×MIC of most treatments could reach more than 40％, but the CRRT dose was 35 m L·kg-1·h-1, and the total dose of meropenem was 2 g per day, which could not reach the pharmacodynamic index. CONCLUSION For sepsis patients with CRRT treated with meropenem, 500 mg q6 h administration regimen is recommended for sensitive pseudomonas aeruginosa. If it is a mediator, the dosage and frequency of meropenem should be increased. The total daily dose of meropenem is 2 g, which can not meet the pharmacodynamic index. There is no obvious advantage in load dose. It is suggested that therapeutic drug monitoring should be carried out to achieve the individualization of administration.

Purpose: Genistein belongs to the group of isoflavones, which include powerful anticancer agents. Its antitumor properties have been intensively described in many cancers, but related studies assessing ovarian cancer are scarce. The aim of this study was to develop a new method of the underlying mechanisms of genistein's effects and broaden the perspective of targeted therapies in ovarian carcinoma. Materials and methods: Genistein targets were searched in the DrugBank database. Prediction of drug interactions with targets (including secondary targets) was performed with STRING database. Interaction pairs with overall score above 0.9 were recorded for protein-protein interaction (PPI) network generation based on the Cytoscape software. Genes with intense interconnections were grouped into a module. Then, PPI network modules with significance were assessed using Molecular Complex Detection (MCODE) analysis tool. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for the critical genes. Furthermore, disease targets were searched in Comparative Toxicogenomics Database (CTD). The overlapping targets were studied using a Kaplan-Meier analysis to evaluate ovarian carcinoma survival. Results: A total of 13 direct targets and 372 secondary targets were identified for genistein and further analyzed with the MCODE analysis tool to identify critical genes. The top 72 genes were further assessed with KEGG. Then, the term "ovarian cancer" was searched in CTD, and 123 genes associated only with the marker "T" or "M" were recorded. Next, seven overlapping genes (CDKN1B, PTEN, EGFR, MAPK1, MAPK3, PIK3C, and AKT1) resulting from the intersection of three pathways and 123 genes were obtained from CTD. Elevated CDKN1B amounts showed correlation with overall survival (log-rank P=0.021) according to Kaplan-Meier analysis. Conclusion: The current findings indicated that drug-target-disease network analysis represents a useful tool in gene-phenotype connectivity for genistein in ovarian cancer. Our result also showed that CDKN1B is worthy of further research.

目的：研究益脑方改善记忆障碍模型小鼠学习记忆的药效学作用。方法连续灌服低、中、高剂量益脑方30d后，以东莨菪碱建立记忆障碍动物模型，并采用跳台法、穿梭箱法、Morris水迷宫法、避暗法检测小鼠的学习记忆能力的变化。结果与模型对照组相比，中、高剂量益脑方可显著延长小鼠跳台潜伏期并减少其5min内跳台错误次数，缩短小鼠穿梭箱及Morris水迷宫上台潜伏期，并可显著逆转由造模引起的超氧化物歧化酶（SOD）活力及乙酰胆碱（Ach）含量下降的作用（P＜0．05）。结论益脑方能显著改善记忆障碍模型小鼠的学习记忆能力。