老年人抗菌药物的合理应用

对老年人药代动力学的特点,各类抗菌药物的药理作用、适应症以及在老年病人中的不良反应进行综述,从而提出老年人合理应用抗菌药物的具体措施,为临床治疗老年感染性疾病提供理论依据。     

抗菌药物致血液系统不良反应分析

近年来,随着抗菌药物在临床上的广泛应用,抗菌药物相关不良反应也越来越引起人们的关注。其中,由于抗菌药物所引起的血液系统不良反应严重影响了患者的身体健康和医生的药物选择。例如,部分β-内酰胺类抗生素可以引起凝血功能障碍和溶血性贫血,氯霉素、磺胺等可以引起再生障碍性贫血,利奈唑胺可以引起血小板减少和贫血等。正确认识各种抗菌药物所引起的血液系统不良反应及其机制,对于临床抗菌药物的选择具有重要意义。本文针对临床常见抗菌药物引起的血液系统不良反应及其机制进行综述,以期为临床抗菌药物的选择提供参考。     

抗菌药物在不同人群中的应用

抗菌药物在预防及治疗疾病中占据重要地位,如在新生儿期,妊娠期、哺乳期等应用广泛,现报道如下。1抗菌与耐药自1928年发现青霉素以来,抗感染药物至今国内外已大量使用,临床各科均应用较多,挽救了很多人的生命,但它具有两重性。由于各种原因,细菌耐药性发展快而严重,感染性疾病又面临严重威胁。有的细菌含有多种耐抗菌药物基因,抗菌药物在临床、养殖业是否合理使用已成为公共卫生问题。     

抗菌药物PK/PD与给药方案优化

药物代谢动力学(PK)和药物效应动力学(PD)是药理学的重要组成部分.PK/PD的研究结合了PK与PD的研究方法,旨在研究某一给药剂量相应的时间-效应过程.目前随着PK与PD研究的日益深入,对药物的体内过程和药效的相关性的进一步了解,使得PK/PD的研究已成为现代药物治疗学的热点.本文对抗菌药物的PK/PD研究进展和PK/PD参数指导给药方案设计进行综述.     

利用蒙特卡洛模拟程序优化抗菌药物治疗

合理的抗菌药物应用是临床抗感染治疗成败的关键,由于抗菌药物在不同群体存在药物动力学差异,往往需要个体化用药.目前临床常用几种抗菌药物的给药剂量预估方法包括回归分析法、群体模型列线图以及蒙特卡洛模拟,本文综合比较3种方法的优劣,为临床安全合理使用抗菌药物提供参考.     

持续性血液净化在急性肾功能衰竭治疗中的临床应用研究

目的 探讨持续性血液净化在急性肾功能衰竭治疗中的临床应用效果.方法 30例急性肾功能衰竭患者,依据随机数字表法分为对照组与试验组,各15例.试验组患者接受持续性血液净化治疗,对照组患者接受间歇性血液净化治疗.比较两组治疗前和治疗2个月后的尿酸(UA)、血肌酐(Scr)、尿素氮(BUN)、白细胞介素6(IL-6)、C反应...     

儿童血液系统疾病抗菌药物使用分析

目的:分析儿童血液系统疾病抗菌药物的使用情况,促进抗菌药物的合理使用.方法:利用合理用药监测系统( PASS)随机抽取苏州大学附属儿童医院血液科2011年1～8月住院患儿病历145例,对抗菌药物的使用方案、使用种类、疗效、联用情况、用药合理性等进行统计、分析.结果:使用抗菌药物的有64例(44.14％).头孢菌素类、碳青霉烯类和青霉素类的使用率分别为38.37％、32.56％和8.14％;头孢哌酮/舒巴坦钠、美罗培南和头孢美唑的用药频次居前3位;联用率为21.90％;临床有效率为93.75％.结论:我院儿童血液病并发感染的抗菌药物应用基本合理且效果明显,但儿童血液系统疾病抗菌药物的合理使用仍有待进一步研究.     

血液肿瘤患者抗菌药物的综合应用分析

血液肿瘤患者免疫功能低下,随时面临各类严重感染,临床上多采用广覆盖、多联合的经验性抗感染治疗,且抗菌药物使用级别高。本次调研发现恶性血液病患者存在抗菌药物预防使用不合理等问题。此外,药物不良反应发生率较高、治疗窗窄的抗菌药物如万古霉素、伏立康唑的血药浓度达标率偏低,临床应加强用药管理,结合病原学检查及血药浓度监测实现精准治疗。     

Dosing of antibiotics in critically ill patients undergoing renal replacement therapy

On September 11, 1945 Maria Schafstaat was the first patient who successfully underwent a dialysis treatment for acute kidney injury (AKI), formerly known as acute renal failure. Since then, the number of patients with AKI is increasing worldwide. Today AKI is generally one feature of a multiple organ dysfunction syndrome (MODS), which develops in response to major surgery, cardiogenic shock or sepsis. Several clinical studies have shown that early and appropriate antibiotic therapy in those patients is of utter importance, yet it remains one of the most difficult challenges to meet. Even in critically ill patients with conserved renal function a myriad of pathophysiological changes, resulting in increased volume of distribution, decreased protein binding and altered hepatic drug clearance, makes appropriate antibiotic dosin difficult. Adequate pharmacotherapy, i.e. dose of anti-infective agens is becoming even more complicated if it has to be tailored to counteract their removal by different modes and intensities of renal replacement therapy. This review summarizes our sparse knowledge about pharmacokinetic studies and dosing recommendations of drugs in patients with AKI undergoing continuous renal replacement therapies (CRRTs) such as continuous venovenous hemofiltration (CVVH) as well as extended dialysis (ED), an increasingly used method to treat patients with AKI in the intensive care setting. We reflect on failure of several large prospective controlled studies to show a survival benefit of higher doses of renal replacement therapy, a finding that might be caused by the fact that we still adhere to dosing guidelines for antibiotics which are at best ineffectual but might also lead to potentially dangerous underdosing of these life saving drugs. Lastly we address possible strategies to overcome the lack of knowledge, the lack of data and the lack of interest in this important area of critical care medicine. Improvement of clinical outcomes and reduction of antibiotic resistance in this patient population will require nephrologist, intensivists and pharmacists to work together.     

Population pharmacokinetics of meropenem in critically ill patients undergoing continuous renal replacement therapy

BACKGROUND AND OBJECTIVE: Meropenem is a carbapenem antibacterial frequently prescribed for the treatment of severe infections in critically ill patients, including those receiving continuous renal replacement therapy (CRRT). The objective of this study was to develop a population pharmacokinetic model of meropenem in critically ill patients undergoing CRRT. PATIENTS AND METHODS: A prospective, open-label study was conducted in 20 patients undergoing CRRT. Blood and dialysate-ultrafiltrate samples were obtained after administration of 500 mg, 1000 mg or 2000 mg of meropenem every 6 or 8 hours by intravenous infusion. The data were analysed under the population approach using NONMEM version V software. Age, bodyweight, dialysate plus ultrafiltrate flow, creatinine clearance (CL(CR)), the unbound drug fraction in plasma, the type of membrane, CRRT and the patient type (whether septic or severely polytraumatized) were the covariates studied. RESULTS: The pharmacokinetics of meropenem in plasma were best described by a two-compartment model. CL(CR) was found to have a significant correlation with the apparent total clearance (CL) of the drug during the development of the covariate model. However, the influence of CL(CR) on CL differed between septic and polytraumatized patients (CL = 6.63 + 0.064 x CL(CR) for septic patients and CL = 6.63 + 0.72 x CL(CR) for polytraumatized patients). The volume of distribution of the central compartment (V(1)) was also dependent on the patient type, with values of 15.7 L for septic patients and 69.5 L for polytraumatized patients. The population clearance was 15 L/h, and the population apparent volume of distribution of the peripheral compartment was 19.8 L. From the base to the final model, the interindividual variabilities in CL and the V(1) were significantly reduced. When computer simulations were carried out and efficacy indexes were calculated, it was shown that polytraumatized patients and septic patients with conserved renal function may not achieve adequate efficacy indexes to deal with specific infections. Continuous infusion of meropenem is recommended for critically septic patients and polytraumatized patients when pathogens with a minimum inhibitory concentration (MIC) of > or =4 mg/L are isolated. Infections caused by pathogens with an MIC of > or =8 mg/L should not be treated with meropenem in polytraumatized patients without or with moderate renal failure because excessive doses of meropenem would be necessary. CONCLUSION: A population pharmacokinetic model of meropenem in intensive care patients undergoing CRRT was developed and validated. CL(CR) and the patient type (whether septic or polytraumatized) were identified as significant covariates. The population pharmacokinetic model developed in the present study has been employed to recommend continuous infusion protocols in patients treated with CRRT.     

Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy

Data on the optimal amikacin regimen during continuous renal replacement therapy (CRRT) are scarce and the proposed loading dose of 10mg/kg may result in inadequate drug levels. The aim of this study was to describe the pharmacokinetics of a 25 mg/kg first dose of amikacin in septic shock patients treated with CRRT. Serum samples were collected before (t=0 h) and at 1 (peak), 1.5, 4.5, 8 and 24 h after a 30-min amikacin infusion in 13 consecutive patients treated with a combination of amikacin and β-lactam. Blood amikacin levels were measured using a validated fluorescence polarisation immunoassay method. In 9 patients (69%) the peak concentration was >64 mg/L, which corresponds to eight times the minimal inhibitory concentration breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Enterobacteriaceae and Pseudomonas aeruginosa (susceptible <8 mg/L, resistant >16 mg/L). The median (range) total volume of distribution was 0.50 L/kg (0.22-4.05 L/kg), the elimination half-life was 6.5h (4.5-279.6h) and total drug clearance (CL) was 1.26 mL/min/kg (0.1-3.30 mL/min/kg). Only three patients had drug concentrations at 24h (C(min)) of <5mg/L and the median predicted time needed to reach this value was 34 h (14-76 h). There was no correlation between CRRT parameters and C(min), CL or the time to C(min)<5mg/L. In septic shock patients treated with CRRT, a first dose of ≥ 25 mg/kg amikacin is therefore required to reach therapeutic peak concentrations. However, as drug clearance is reduced, amikacin concentrations remained above the threshold of renal toxicity at 24h. The therapeutic benefit of high-dose aminoglycoside therapy should be balanced with its potential renal effects in septic patients receiving CRRT.     

Population pharmacokinetics and simulations of imipenem in critically ill patients undergoing continuous renal replacement therapy

Various dose regimens of imipenem have been prescribed in critically ill patients undergoing continuous renal replacement therapy (CRRT) but there are limited information on its pharmacokinetics (PK) and treatment efficacy. The aim of this study was to describe the population PK of imipenem in patients receiving CRRT, and utilize this model to inform optimal dosing regimens using pharmacokinetics/pharmacodynamics (PK/PD) target as a surrogate marker for treatment efficacy. Population PK modelling was undertaken in 20 patients receiving CRRT to characterize variabilities and identify influential covariates. Monte Carlo simulations were performed to evaluate differences in probability of target attainment (PTA) between empirically used dosing regimens (0.5 g q6h, 1 g q8h, and 1 g q6h), and to explore the impact of CRRT intensity and identified covariates on target attainment. Imipenem concentration data were adequately described using a one-compartment model. Residual diuresis and burn injury were identified modifiers for imipenem endogenous clearance. The simulations showed that the impact of CRRT intensity on target attainment is clinically irrelevant, whereas urine output and burn injury influence PTA for pathogens with an MIC ≥ 4 mg/L. At an MIC ≤ 2 mg/L, satisfactory PTAs (>80%) were achieved for all three investigated dose regimens regardless of urine output, burn injury, and CRRT intensity. Our results indicate that from a safety perspective, 0.5 g q6h imipenem is optimal in these patients for pathogens with an MIC ≤ 2 mg/L, and 1 g q6h is recommended for non-burn patients with anuria against MIC 4–16 mg/L.     

AKIN分期在急性肾损伤患者选择连续性肾脏替代治疗时机的意义

目的 探讨AKIN分期在创伤后急性肾损伤(AKI)患者进行连续性肾脏替代治疗(CRRT)时机选择中的应用价值.方法 创伤后AKI患者84例按AKIN标准分为1期(32例)、2期(22例)和3期(30例).均采用CRRT治疗,检测治疗前和治疗24 h后APACHEⅡ评分、氧合指数、血清肌酐、血尿素氮、血钾和血乳酸值,比较三组患者的病死率.结果 AKIN 3期组患者病死率为80.0％(24/30),AKIN 2期组病死率为68.2％ (15/22),均明显高于AKIN 1期组的37.5％(12/32) (P＜0.05).CRRT治疗24 h后,三组患者APACHEⅡ评分、血清肌酐、血尿素氮和血钾均明显下降(P＜0.05);治疗24 h后,AKIN 1期患者的氧合指数显著升高、血乳酸值显著降低(P＜0.05),但在AKIN 2、3期患者则无明显变化.结论 AKIN标准对创伤后AKI患者的早期诊断和预后判断有重要指导意义.     

美罗培南在连续性肾脏替代治疗患者中的药代动力学

目的研究美罗培南(碳青霉烯类抗生素)在连续性肾脏替代治疗(CRRT)患者的药代动力学特点。方法10名CRRT患者在30 min内匀速静滴美罗培南1.0 g,给药后不同时间收集血样和置换液,用HPLC检测药物浓度,用3P97软件计算药代动力学参数。结果在静脉滴注美罗培南1.0 g后。血药浓度-时间数据以二室模型拟合最佳,t_(1/2α)为(0.25±0.06)h,t_(1/2β)为(6.96±2.17)h,C_(max)为(48.50±12.32)mg·L~(-1),Vc为(24.48±7.21)L,AUC为(203.20±48.61)mg·h·L(-1)。结论美罗培南在CRRT患者的主要药代动力学参数与健康者有较大的差异,临床应用时应适当减少剂量或延长给药间隔。     

连续性肾脏替代治疗中抗菌药物剂量的调整

由于接受连续性肾脏替代治疗（CRRT）的危重患者体内病理生理学的改变,抗菌药物的药动学和药效学参数会发生较大变化,因而最终影响了抗菌药物的效能。本文综述CRRT时影响药物清除的主要因素,并提出CRRT患者使用抗菌药物的剂量建议,为临床合理用药提供参考。     

慢性肾病患者行连续性肾脏替代治疗时抗菌药物治疗方案调整的分析与思考

危重患者行连续性肾脏替代治疗（CRRT）时,受CRRT模式、药物特性及患者病生理状态等因素的影响,抗菌药物的药代动力学和药效动力学参数改变,进而影响抗菌药物给药方案的调整。本文就1例行CRRT治疗的慢性肾病患者应用万古霉素的病例进行分析,探讨CRRT时抗菌药物剂量调整的影响因素。提供个体化给药方案,保证了患者抗感染治疗的安全性和有效性。