某院肠杆菌科细菌耐药性与抗菌药物使用强度时间相关性分析

目的　探讨肠杆菌科细菌耐药性与抗菌药物使用强度时间相关性,为优化抗菌药物临床选用提供依据。方法　采用回顾性调查方法,统计连云港市第一人民医院2016年1月至2021年12月期间住院患者各类标本中检出肺炎克雷伯菌、大肠埃希菌对哌拉西林/他唑巴坦、美罗培南以及亚胺培南耐药率和同期β‐内酰胺酶复合制剂、碳青霉烯类抗菌药物使用强度。采用线性回归分析抗菌药物季度使用强度和细菌季度耐药率变化趋势,运用互相关函数分析抗菌药物季度使用强度与细菌季度耐药率之间时间相关性。结果　6年期间肺炎克雷伯菌对哌拉西林/他唑巴坦（P<0.001）、美罗培南（P=0.001）耐药率均呈上升趋势,大肠埃希菌对哌拉西林/他唑巴坦耐药率逐渐下降（P<0.001）。研究期间碳青霉烯类抗菌药物使用强度呈上升趋势（P=0.008）,β-内酰胺酶复合制剂类抗菌药物使用强度呈下降趋势（P=0.032）。肺炎克雷伯菌对哌拉西林/他唑巴坦耐药率与碳青霉烯类抗菌药物使用强度高度同步（r=0.812,Lag=0,P=0.022）,对美罗培南（r=0.704,Lag=1,P=0.037）和亚胺培南（r=0.885,Lag=1,P=0.005）耐药率与碳青霉烯类抗菌药物使用强度均呈显著正相关。β-内酰胺酶复合制剂类抗菌药物使用强度与大肠埃希菌（r=0.587,Lag=3,P=0.045）和肺炎克雷伯菌（r=0.531,Lag=2,P=0.039）对哌拉西林/他唑巴坦耐药率均呈正相关。结论　医院肠杆菌科细菌耐药率与抗菌药物使用强度存在一定时间相关性,临床应优化抗菌药物合理选用,遏制肠杆菌科细菌耐药性进展。     

碳青霉烯类抗菌药物对肠杆菌科细菌及非发酵菌的防突变浓度研究

目的评价碳青霉烯类抗菌药物对临床分离的100株大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌的防突变浓度(MPC)。方法采用琼脂稀释法测定碳青霉烯类抗菌药物(亚胺培南、美洛培南、厄他培南和多利培南)对临床分离的肠杆菌科和非发酵菌菌株的最小抑菌浓度(MIC)及MPC,并计算MPC/MIC比值。结果碳青霉烯类抗菌药物对肠杆菌科敏感株的MPC为0.25~4.0μg·m L~(-1),耐药株MPC为8.0~>64.0μg·m L~(-1)。多利培南、亚胺培南、美洛培南对非发酵菌敏感株的MPC为2.0~4.0μg·m L~(-1),耐药株MPC为8.0~128μg·m L~(-1)。肠杆菌科细菌和非发酵菌敏感株的MPC/MIC比值为2~4,耐药株多为8~>16。结论碳青霉烯类抗菌药物对肠杆菌科和非发酵菌敏感株的MPC为0.125~4.0μg·m L~(-1),MPC/MIC比值为2~4;对耐药株的MPC为2.0~128.0μg·m L~(-1),MPC/MIC比值为8~>16。     

我院2010-2012年肠杆菌科细菌耐药性研究

目的：了解某儿童医院2010-2012年临床分离的肠杆菌科菌群分布及其耐药性。方法：收集2010-2012年该院临床分离的肠杆菌科细菌2494株,对其药敏试验结果进行统计、分析。结果：2494株肠杆菌科菌株中,分离最多的是肺炎克雷伯菌1069株（42．9％）,其次是大肠埃希菌1044株（41．9％）和阴沟肠杆菌134株（5．4％）。肠杆菌科细菌对常用抗菌药物均有不同程度耐药,对哌拉西林／他唑巴坦、头孢噻肟、头孢他啶、头孢吡肟的耐药率较低（〈27．7％）,对亚胺培南、美罗培南的耐药率最低（〈1．3％）。结论：肠杆菌科细菌对多数抗菌药物有不同程度的耐药,对碳青霉烯类抗菌药物最为敏感。定期进行耐药性监测有助于了解医院细菌耐药性变迁,为临床经验用药提供依据。     

碳青霉烯类耐药的肠杆菌科细菌实验室研究现状

<正>碳青霉烯类抗生素主要包括亚胺培南、美罗培南、厄他培南等,具有抗菌谱广、抗菌活性强、并具有对β-内酰胺酶稳定及毒性低等特点,已经成为临床治疗严重革兰阴性菌感染的最有效的途径。其疗效在临床上已得到广泛认可,近年随着此类药物的大量使用甚至过度治疗,碳青霉烯类耐药肠杆菌科细菌(CRE)不断增加。因其质粒携带耐药基因,CRE在细菌之间迅速传播,极易在病区内传播流行,对人体健康构成严重的威胁。本文就CRE流     

某院新生儿肠杆菌感染败血症耐药性及其抗菌药物治疗分析

目的 对新生儿肠杆菌感染败血症耐药性和抗菌药物治疗进行分析,旨在为临床用药提供参考。方法 回顾性分析武汉大学人民医院2020年1月—2021年12月新生儿科诊断为败血症且血培养肠杆菌的住院患儿,对患儿的一般临床特征、病原菌、药敏试验结果、产酶类型以及患儿的治疗方案及临床结局进行收集统计。结果 共收集肠杆菌感染败血症患儿30例,主要病原菌为大肠埃希菌与肺炎克雷伯菌,大肠埃希菌主要耐药机制为耐碳青霉烯酶,且以产B类金属β-内酰胺酶型为主,主要治疗方案为氨曲南单药治疗;肺炎克雷伯菌主要耐药机制为产超广谱β-内酰胺酶,主要治疗药物为碳青霉烯抗菌药物,接受治疗的患儿均取得较好的治疗效果。结论 耐碳青霉烯大肠埃希菌推荐给予氨曲南治疗,产超广谱β-内酰胺酶的肺炎克雷伯菌可优先给予碳青霉烯类抗菌药物,本研究可为临床多重耐药肠杆菌感染败血症新生儿提供用药参考。     

对碳青霉烯类抗菌药不敏感肠杆菌科细菌耐药性分析

目的:了解我院临床分离的对碳青霉烯类抗菌药不敏感的肠杆菌科细菌对常用抗菌药物的耐药性。方法:收集2013年4月-2014年3月我院临床分离的30株对碳青霉烯类抗菌药不敏感的肠杆菌科细菌,使用由美国BD公司生产的Phoenix-100全自动细菌鉴定/药敏系统进行菌株鉴定和药敏试验,产碳青霉烯酶的表型确证采用改良Hodge试验。结果:30株对碳青霉烯类抗菌药不敏感的肠杆菌科细菌对多黏菌素、阿米卡星和复方新诺明的敏感率较高,依次为100.0%,73.3%和66.7%;对碳青霉烯类抗菌药亚胺培南和美罗培南的耐药率分别为100.0%和86.7%;对氨苄西林、头孢菌素类、含β-内酰胺酶抑制剂的复合制剂和单环β-内酰胺类抗菌药的耐药率均为100.0%;对其余抗菌药的耐药率均在60.0%以上。30株菌的改良Hodge试验阳性率为86.7%(26/30)。结论:对碳青霉烯类抗菌药不敏感的肠杆菌科细菌对常用抗菌药物表现为高度多重耐药,为高产碳青霉烯酶菌株。为防止产碳青霉烯酶基因的流行,临床应合理使用抗菌药物并加强对肠杆菌科细菌产碳青霉烯酶的监测。     

25株肠杆菌科菌株对碳青霉烯类抗菌药物的耐药性分析

目的:分析肠杆菌科菌株对碳青霉烯类抗菌药物的耐药性,为临床合理使用碳青霉烯类抗菌药物所提供参考。方法:选取2015年9月—2016年9月间分离出的25株肠杆菌科菌株,采用改良后的Hodge实验法对菌株进行药敏试验和鉴定,分析其对碳青霉烯类抗菌药物的耐药情况。结果:肠杆菌科菌株对多黏菌素敏感,其敏感率为100.00%;对阿米卡星和复方磺胺甲噁唑敏感率依次为76.40%和68.20%;而对氨苄西林、头孢菌素和亚胺培南的耐药性均为100.00%;对美罗培南的耐药性为87.40%;经Hodge检测阳性率为84.00%。结论:碳青霉烯类抗菌药物对肠杆菌科菌株在临床上均表现为多重且高度耐药性。     

三种碳青霉烯类抗生素的体外抗菌作用

为评价亚胺培南、帕尼培南与美罗培南的体外抗菌作用 ,以琼脂对倍稀释法测定三者对 2 2 5株临床分离菌的最低抑菌浓度 (MIC) ,并与相关抗菌药物进行比较。结果 ,三种碳青霉烯类抗生素对肠杆菌科细菌具高度抗菌活性 ,对铜绿假单胞菌、不动杆菌属、粪肠球菌等亦具良好抗菌作用。帕尼培南与亚胺培南体外抗菌作用相仿 ,两者对肺炎克雷伯氏菌、肠杆菌属等革兰氏阴性菌作用略逊于美罗培南。三种碳青霉烯类抗生素体外抗菌作用优于头孢他啶、β-内酰胺类抗生素与β-内酰胺酶抑制剂合剂、氟喹诺酮类等其它受试药物。结果表明 ,碳青霉烯类抗生素是治疗多重耐药菌所致院内感染、免疫缺陷者感染和严重需氧菌与厌氧菌混合感染的适用药物。     

铜绿假单胞菌对不同抗菌药物的耐药性与碳青霉烯类抗菌药物使用的相关因素分析

目的:分析铜绿假单胞菌对不同抗菌药物的耐药性与碳青霉烯类抗菌药物使用的相关因素。方法:抽取2015年7月—2017年6月间收治的住院患者送检标本检验结果资料,统计其铜绿假单胞菌对不同抗菌药物的耐药率,以及其对碳青霉烯类抗菌药物的耐药率及碳青霉烯类抗菌药物的使用量、DDDs,分析两者间的相关性。结果:2年间碳青霉烯类抗菌药物的使用量由2015年第3季度DDDs 421.88增至2017年第2季度DDDs788.75,铜绿假单胞菌对碳青霉烯类的耐药率也逐年增长,而对美罗培南的耐药率由14.36%增至34.70%,对亚胺培南的耐药率由19.88%增至41.18%;显示铜绿假单胞菌对美罗培南、亚胺培南的耐药率与美罗培南、碳青霉烯类抗菌药物的使用量之间具有相关性。结论:各碳青霉烯类抗菌药物的使用量与铜绿假单胞菌对美罗培南、亚胺培南的耐药率呈正相关。     

我院肠杆菌科细菌对碳青霉烯类抗菌药物的耐药性分析

目的:探讨我院肠杆菌科细菌对碳青霉烯类抗菌药物的耐药性。方法:收集我院2014年1-4月分离的肠杆菌科细菌404株,分析其标本分布,选取57株对亚胺培南(IMI)或厄他培南(ETP)最低抑菌浓度(MIC)≥2μg/ml中介或耐药的肠杆菌科细菌,采用改良Hodge试验检测其碳青霉烯酶(KPC),纸片扩散法(K-B)检测其对美罗培南(MPN)的敏感性(抑菌环直径)。结果:57株肠杆菌科细菌对IMI敏感率为88.9%,对ETP敏感率为96.0%,对MPN敏感率为99.3%;8株细菌改良Hodge试验阳性。结论:对碳青霉烯类抗菌药物耐药的肠杆菌科细菌数量和种类检出率较高,应引起临床高度重视。     

耐碳青霉烯类肺炎克雷伯菌医院感染、耐药性及治疗的研究进展

医院感染的主要病原菌是肠杆菌科细菌。由于临床上对于抗菌药物的不合理使用,使得耐碳青霉烯类肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)的检出率不断增加,而耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant Klebsiella     

耐碳青霉烯类肺炎克雷伯菌医院感染、耐药性及治疗的研究进展

医院感染的主要病原菌是肠杆菌科细菌。由于临床上对于抗菌药物的不合理使用,使得耐碳青霉烯类肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)的检出率不断增加,而耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae,CRKP)是临床所分离CRE中最为常见的。本文将从CRKP感染现状、影响因素、耐药机制等方面进行介绍,提高人们对CRKP感染的重视和控制,以期对临床治疗CRKP提供有效的抗菌药物及联合治疗方案。     

PK/PD模型结合蒙特卡洛模拟评价和优化耐碳青霉烯类铜绿假单胞菌抗菌药物给药方案

目的： 评价和优化耐碳青霉烯类铜绿假单胞菌感染抗菌药物给药方案。方法： 收集中山市人民医院2019年耐碳青霉烯类铜绿假单胞菌对头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星耐药监测报告,确定头孢他啶、头孢吡肟、哌拉西林钠他唑巴坦和阿米卡星治疗方案,根据各抗菌药物的PK/PD模型,运用蒙特卡洛模拟计算4种抗菌药物不同给药方案的达标概率（PTA）和累积反应分数（CFR）,评价疗效和优化出最佳初始给药方案。结果： 4种抗菌药物15种给药方案CFR均<90%。当最低抑菌浓度（MIC）≤ 2 μg·mL^-1时,4种抗菌药物常规剂量下的给药方案均能达到满意的治疗效果,当MIC ≤ 16 μg·mL^-1时,可目标性选择头孢他啶2 g（q8h）、头孢吡肟2 g（q8h）和哌拉西林钠他唑巴坦4.5 g（q8h）给药方案治疗,当MIC=32 μg·mL^-1时,只有哌拉西林钠他唑巴坦4.5 g（q6h）给药方案PTA>90%,当MIC>32 μg·mL^-1时,所有给药方案PTA均<90%。4种抗菌药物MIC值的敏感相关性为范围-88.9%~-96.7%。结论： 在CRPA感染经验性治疗时,单药治疗并不能达到满意的抗感染治疗效果,应考虑联合用药,可选用较高剂量和增加给药频次的抗假单胞菌β内酰胺类抗菌药联合阿米卡星。MIC值是影响4种抗菌药物治疗效果的最主要因素,临床上应重视细菌耐药的培养,可根据MIC值调整给药方案进行目标治疗。     

2015-2017年某儿童医院耐碳青霉烯类肠杆菌科细菌分布及耐药性分析

目的 分析某三甲儿童医院临床标本分离耐碳青霉烯类肠杆菌科细菌(CRE)的分布及耐药情况,为临床抗感染治疗及医院感染防控提供参考。方法 收集2015年1月1日-2017年12月31日期间住院患儿临床标本分离出CRE菌株的药敏数据及相关资料,对数据进行统计分析。结果 住院患儿临床标本共分离CRE菌株723株,总检出率15.47%,主要为肺炎克雷伯菌590株、大肠埃希菌77株、阴沟肠杆菌15株。标本类型主要为痰液535株、血液43株、肺泡灌洗液35株。CRE菌株分布广泛,科室来源主要为新生儿重症监护室、早产儿病房、内科监护室。CRE对β-内酰胺类抗菌药物耐药率在90%以上,对氨基糖苷类、喹诺酮类、四环素等抗菌药物耐药率在81%以下。结论 CRE菌株的检出率呈现出较高水平,CRE的临床分布广泛且对常用抗菌药物耐药率高,应多部门联动加强对CRE的监测与防控,合理应用抗菌药物。     

2018—2020年多中心耐碳青霉烯类肠杆菌目细菌的流行病学特征及耐药性分析

摘要：目的 了解多中心耐碳青霉烯类肠杆菌目细菌的流行病学特征,为临床抗感染治疗提供依据。方法 收集2018年1 月—2020年12月全国不同地区11家医院6123株耐碳青霉烯类肠杆菌目细菌(carbapenem-resistant Enterobacterales,CRE)临床分离 株,按统一方案和标准进行菌株鉴定和体外药物敏感性试验,药敏结果参照2020版CLSI标准判读,并用WHONET 5.6软件统计 分析。结果 3年间CRE检出率分别是6.4%(1897/29525)、6.8%(2186/32239)、7.3%(2171/29816),其中耐碳青霉烯类肺炎克雷伯 菌(CR-KPN)、大肠埃希菌(CR-ECO)的3年总检出率分别是13.2%和2.0%。CRE菌株主要分离自痰液标本43.8%(2681/6123),其次 是尿液标本16.0%(977/6123)、血液标本8.1%(496/6123)和分泌物标本4.5%(278/6123)。不同种属耐碳青霉烯类肠杆菌目细菌中不 同标本类型的占比不同,CR-KPN以痰液标本为主,CR-ECO以尿液标本为主。不同科室的CRE检出率有所不同,以ICU检出最 高。体外药敏结果显示,CRE对临床常用抗菌药物高度耐药,不同菌属CRE对临床常用抗菌药物的耐药率略有不同。CR-KPN和 CP-ECO对大多数抗菌药物的耐药率高于耐碳青霉烯类阴沟肠杆菌(CR-ECL),对替加环素、多黏菌素B的体外抗菌活性较高。结 论 CRE检出呈上升趋势,各地区需加强本地区CRE监测,加强院内感染防控措施,有效遏制CRE的暴发流行。     

A reappraisal of current dosing strategies for intravenous fosfomycin in children and neonates

The rising incidence of multi-drug resistant bacterial pathogens has renewed interest in the long-known antibacterial fosfomycin. Not least because of its low toxicological potential, there is good clinical experience with intravenous fosfomycin for various Gram-positive and Gram-negative infections in the treatment of children and neonates. However, the current dosing recommendations for intravenous fosfomycin vary widely in paediatric patients. In the present review, we summarized available plasma pharmacokinetic data derived from neonates or children following intravenous administration of fosfomycin. Subsequently, we used this information for recalculation of different dosing strategies and simulated a variety of clinically applied dosing regimens. The percentage of time above the minimal inhibitory concentration (T>MIC) was calculated for each dosing strategy, as this pharmacokinetic-pharmacodynamic parameter was shown to be most predictive of antimicrobial and clinical success of fosfomycin treatment. Our data corroborate the current practice of selecting the dosage of intravenous fosfomycin primarily on the basis of bodyweight and age in paediatric patients. As with other 'time-dependent' antibacterials, a dosing interval of 6-8 hours should be preferred over 12 hours except for immature neonates. Given a T>MIC target of 40-70%, currently recommended dosing strategies appear to be insufficient in children aged 1-12 years, if pathogens with MICs of ≥32 mg/L are suspected and subjects are presenting with normal renal function. Likewise, the lowest recommended daily dose for neonates and infants (aged up to 12 months) of 100 mg/kg bodyweight of fosfomycin should be considered only for pre-term neonates with a postmenstrual age below 40 weeks.     

Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics

The judicious use of antibiotics to combat infections in children relies upon appropriate selection of an agent, dose and duration to maximise efficacy and to minimise toxicity. Critical to dose optimisation is an understanding of the pharmacokinetics and pharmacodynamics of available drugs. Optimal dosing strategies may take advantage of pharmacokinetic/pharmacodynamic (PK/PD) principles so that antibiotic dosing can be individualised to assure effective bacterial killing in patients who have altered pharmacokinetics or who have infections with less susceptible or resistant organisms. This review will outline the fundamentals of antimicrobial pharmacokinetics/pharmacodynamics through discussion of antibacterial agents most often used in children. We aim to highlight the importance of dose optimisation in paediatrics and describe non-conventional dosing strategies that can take advantage of PK/PD principles at the bedside.     

Optimizing therapy with antibacterial agents: use of pharmacokinetic-pharmacodynamic principles in pediatrics

The appropriate dosage of antibacterial agents is essential in achieving both clinical and microbiologic success in the treatment of infections in children. By using in vitro experimental data and animal model outcome data, the pharmacokinetic-pharmacodynamic (PK-PD) parameters predictive of antibacterial effect have been elucidated. For time-dependent drugs such as beta-lactams, the PK-PD parameter of interest is the percentage of time in a dosage interval for which drug concentrations remain above the minimum inhibitory concentration (MIC) of the infecting organism. For concentration-dependent drugs such as aminoglycosides, the PK-PD parameter of interest is the ratio of the area under the plasma concentration-time curve to the MIC. Recent studies using data on clinical and microbiologic outcomes from infected adults and children, combined with data on drug exposure, have confirmed the importance of these parameters and provided estimates of the PK-PD goals of therapy for various antibacterial agents. Application of these PK-PD principles allows rational dosage regimen selection, both for serious infections in critically ill children and for non-life-threatening community-acquired infections.     

Pharmacokinetic and pharmacogenetic determinants and considerations in chemotherapy selection and dosing in infants

INTRODUCTION: There is a lack of high-quality data regarding optimal chemotherapy dosage regimens among infants. Dosing regimens for chemotherapy during the first year of life are commonly based on empiric recommendations extrapolated from older children; however, balancing efficacy and toxicity is critical as severe adverse drug reactions may lead to treatment failure or reduced adherence to needed medications. AREAS COVERED: This review describes pharmacokinetic and pharmacogenetic considerations when administering chemotherapeutic agents to infants. Examples of commonly used agents are provided with practical recommendations for dosing adjustments. EXPERT OPINION: Optimal chemotherapy for children and infants in particular has lagged behind the remarkable progress in cancer treatment and it is clear that far more basic and clinical research are needed with respect to the mechanistic basis of age-dependent differences in pharmacokinetic parameters. More recent studies which have combined pharmacokinetic data with clinical toxicity and outcome data have resulted in a number of more evidence-based guidelines at least for the initial chemotherapy dosing; however, at present, the dosing of chemotherapy drugs in neonates and infants remains largely empiric.     

Individualized dosing regimens in children based on population PKPD modelling: are we ready for it?

Despite profound differences in response between children and adults, and between children of different ages, drugs are still empirically dosed in mg/kg in children. Since maturation of expression and function is typically a non-linear dynamic process which differs between biotransformation routes and pharmacological targets, paediatric dosing regimens should be based on the changing pharmacokinetic-pharmacodynamic (PKPD) relationship in children. In this respect, the population approach is essential, allowing for sparse sampling in each individual child. An example is presented on morphine glucuronidation, for which two covariates were identified and subsequently used to derive a model-based dosing algorithm for a prospective clinical trial in children. Using this novel dosing algorithm, similar morphine concentrations are expected while, depending on age, lower and higher morphine dosages are administered compared to mg/kg/h dosing. As the covariate functions may reflect system-specific information on the maturation of a specific drug-disposition pathway, its use for other drugs that share the same pathway is explored. For this purpose, prospective clinical trials and cross-validation studies are urgently needed. In conclusion, PKPD modelling and simulation studies are important to develop evidence-based and individualized dosing schemes for children, with the ultimate goal to improve drug safety and efficacy in this population.