头孢他啶/阿维巴坦挽救性治疗早产儿耐碳青霉烯类肺炎克雷伯菌感染的效果及安全性病例分析

目的 评估头孢他啶/阿维巴坦(ceftazidime/avibactam,CAZ/AVI)挽救性治疗早产儿耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae,CRKP)感染的效果和安全性。方法 回顾性纳入2020年8月至2022年7月接受CAZ/AVI挽救性治疗的CRKP感染早产儿的临床资料12例,根据用药时是否联合美罗培南,分为联合组(n=5)和单药组(n=7),记录所有患儿临床资料、用药信息、实验室检查结果及不良反应。结果 12例中血流感染5例,肺部感染7例。高剂量美罗培南延时输注或联合磷霉素效果不佳时,超说明书使用CAZ/AVI挽救性治疗,平均治疗时间为(12.00±4.73)d,总体治愈率为66.67%。结论 CAZ/AVI对于早产儿CRKP感染疗效及安全性较高,可作为备选治疗方案。     

头孢他啶-阿维巴坦治疗耐碳青霉烯肺炎克雷伯菌肺部感染的疗效

目的评估头孢他啶-阿维巴坦治疗耐碳青霉烯肺炎克雷伯菌(CRKP)肺部感染的疗效和安全性。方法选取CRKP肺部感染的患者41例,采用头孢他啶-阿维巴坦抗感染治疗,分析其有效性和不良反应发生情况。结果头孢他啶-阿维巴坦治疗CRKP肺部感染的有效率为75.6%,不良反应发生率为9.8%。结论头孢他啶-阿维巴坦治疗CRKP肺部感染有一定的临床疗效,且不良反应发生率较低。     

1例头孢他啶/阿维巴坦治疗碳青霉烯耐药肺炎克雷伯菌血流感染患者的药学监护

目的 探讨临床药师在碳青霉烯耐药肺炎克雷伯菌血流感染药物治疗中的作用。方法 临床药师参与1例碳青霉烯耐药肺炎克雷伯菌血流感染患者的治疗过程,结合专业知识,根据患者实际情况,建议采用注射用头孢他啶阿维巴坦单药治疗方案,并对用药的有效性和安全性进行监护。结果 医生采纳临床药师建议,经治疗后患者体温正常,炎症指标好转,血培养显示无细菌生长。结论 临床药师通过参与临床工作,及时掌握新药的相关知识,为临床医生提供药学信息服务,保障用药的合理性、安全性。     

头孢他啶/阿维巴坦治疗碳青霉烯类耐药肠杆菌感染疗效和安全性的Meta分析

目的 系统评价头孢他啶/阿维巴坦(ceftazidime/avibactam,CAZ/AVI)治疗耐碳青霉烯类肠杆菌/肺炎克雷伯菌(CRE/CRKP)感染的疗效和安全性,以期为临床治疗提供循证依据.方法 计算机检索PubMed、Embase、The Cochrane Library、CBM、CNKI、VIP电子数据库,...     

头孢他啶阿维巴坦对耐碳青霉烯类肺炎克雷伯菌的体外抗菌活性分析

目的 探讨头孢他啶阿维巴坦(CAZ-AVI)对耐碳青霉烯类肺炎克雷伯菌(CRKP)的体外抗菌活性.方法 选取2019年1月至2020年12月空军军医大学第二附属医院临床各科室送检标本分离的肺炎克雷伯菌1075株,进行细菌鉴定及药物敏感性试验.结果 在1075株肺炎克雷伯菌中CRKP共检出168株,检出率为15.6％,碳...     

耐碳青霉烯肺炎克雷伯菌对头孢他啶 /阿维巴坦的耐药情况及其危险因素分析

目的探讨耐碳青霉烯类肺炎克雷伯菌( CRKP)对头孢他啶 /阿维巴坦( ceftazidime/avibactam,CZA)的耐药情况及危险因素。方法选取 2019年 10月至 2022年 5月在西安国际医学中心重症监护病房( intensive care unit,ICU)住院治疗的 CRKP病人 156例,根据 CRKP病人是否对 CZA耐药分为 CZA敏感组( n=111)和耐药组( n=45)。采用微量肉汤稀释法检测 CRKP对 CZA的药敏情况。分析比较 CRKP对 CZA敏感病人和耐药病人的一般资料,多因素 logistic回归分析 CRKP对 CZA耐药的危险因素。比较两组病人住院期间的死亡率。结果 156株 CRKP中 111株( 71.15%)对 CZA敏感, 45株( 28.85%)对 CZA耐药。两组病人在年龄、性别、身体质量指数、标本来源和基础疾病上差异无统计学意义( P>0.05)。在侵入性操作中, CZA耐药组机械通气( 77.78%比 55.86%)、透析( 46.67%比 18.02%)和手术的病人( 77.78%比 54.05%)比例明显高于 CZA敏感组( P<0.05)。同时, CZA耐药组既往接受 CZA治疗的病人比例明显高于 CZA敏感组( 24.44%比 9.01%)差异有统计学意义( P<0.05)。多因素 logistic回归分析显示 CRKP对 CZA耐药的危险因素包括透析、机械通气和既往接受 CZA治,疗( P<0.05)。 CZA耐药组中病人住院期间死亡率( 28.89%)明显高于 CZA敏感组( 10.81%)差异有统计学意义( χ2=7.78,P=0.005)。结论部分 CRKP对 CZA耐药,耐药病人住院期间死亡率高。透析、机械通气和既往接,受 CZA治疗是 CRKP对 CZA耐药的危险因素。     

头孢他啶阿维巴坦不同方案对耐碳青霉烯类肠杆菌感染的有效性与安全性评价

目的:基于重叠加权法比较头孢他啶阿维巴坦(ceftazidime/avibactam, CAZ/AVI)针对耐碳青霉烯类肠杆菌(carbapenem-resistant Enterobacterales, CRE)感染单药与联合治疗方案的有效性与安全性。方法:以非干预方式收集南京鼓楼医院2020年7月至2022年12月使用CAZ/AVI治疗CRE感染患者的基本特征、感染情况、治疗方案和不良反应(adverse reactions, ADRs)等信息,并根据治疗方案分为单药组和联合组。利用重叠权重加权法均衡组间变量差异后对比2组的临床治愈率、微生物清除率、28 d全因死亡率和ADR发生率差异。结果:共收集到单药组患者56例和联合组患者35例。加权后效应值估计结果显示,联合组微生物清除率高于单药组(P=0.015),2组的临床治愈率和28 d全因死亡率无统计学差异。安全性方面,联合组的ADR发生率高于单药组(P=0.028),在胃肠系统方面的ADR发生率存在显著差异(P=0.019)。结论:CRE感染患者使用CAZ/AVI单药或联合方案均有良好疗效,且联合用药相较于单药的微生物清除率更高,...     

1例头孢他啶阿维巴坦联合氨曲南治疗重症肺炎失败后的药物治疗策略分析

本文报道1例耐碳青霉烯类肺炎克雷伯菌所致重症肺炎,先后经替加环素联合美罗培南、头孢他啶阿维巴坦和头孢他啶阿维巴坦联合氨曲南治疗失败后的药物治疗策略。临床药师根据患者临床表现、肾脏功能、感染指标等的动态变化,结合细菌培养/药敏和宏基因组二代测序结果及抗菌药物药动学/药效学特点,提出硫酸黏菌素静脉滴注（75万单位,ivd,q12h,首剂150万单位）并雾化（25万单位,q12h）联合替加环素（100 mg,ivd,q12h,首剂200 mg）为基础的抗感染方案建议,为医生采纳同时实施药学监护,患者肺炎得到控制,转至康复机构。临床药师追踪前沿抗菌药物知识,利用专业优势为临床团队提供有效的技术支持,协助疑难感染病例的诊疗,体现了职业价值。     

Pharmacokinetic drug evaluation of avibactam + ceftazidime for the treatment of hospital-acquired pneumonia

Introduction: Ceftazidime-avibactam (CAZ-AVI) is a combination of a third-generation cephalosporin and a non-β-lactam, β-lactamase inhibitor, recently approved for urinary tract infections and complicated abdominal infections. Moreover, it represents a treatment option for patients with hospital acquired pneumonia (HAP), especially when caused by multidrug-resistant (MDR) bacteria.

Areas covered: The review focuses on the pharmacokinetics (PK) of CAZ-AVI in HAP and on preclinical and clinical studies evaluating PK/pharmacodynamics (PD) in this field.

Expert opinion: In vitro and in vivo data about PK/PD of CAZ-AVI confirm that penetration of CAZ-AVI in the epithelial lining fluid (ELF) represents approximately 30% of the plasma concentrations. Clinical studies documented that CAZ-AVI 2000 mg/500 mg every 8 h is the optimal dose regimen to achieve the PK/PD target attainment in patients with HAP. Thus, CAZ-AVI could represent an option both to treat HAP caused by Gram-negative bacilli (GNB) displaying resistance to most of the antibiotics and to reduce the use of carbapenems, limiting the onset of resistance profiles among GNB. Additional information about specific patients populations, such as critically-ill subjects or pediatric patients, are needed for a more individualized use of CAZ-AVI.     

Pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants

Pharmacokinetics and clinical efficacy of ceftazidime (CAZ) were evaluated in neonates. The results obtained are summarized below. After a bolus intravenous injection of 20 mg/kg CAZ to neonates, peak serum concentrations ranged 55.1-97.4 micrograms/ml with the mean half-life of 2.26 hours in neonates with birth weight of 2,500 g or more, and 59.3-60.7 micrograms/ml with half-lives ranging from 3.98 to 4.22 hours in neonates weighing less than 2,500 g at birth. In the time-course observation, it was noted that the half-life at 2 days after birth was longer than half-lives observed on 4 and 9 days after birth. Four cases were given CAZ for treatment, and 3 cases for prophylaxis of infections, and the clinical efficacy was either excellent or good in all of the cases. Neither adverse effects nor abnormal laboratory findings were observed except rash in 1 case. Intestinal flora was examined in 5 cases. It was found that the effect of CAZ was less than that of LMOX, although some delay was seen in the growth of intestinal flora. There was no vitamin K deficiency in any of 6 cases examined.     

Fundamental and clinical evaluation of ceftazidime in neonates and premature infants

Fundamental and clinical evaluation of ceftazidime (CAZ) were carried out in neonates and premature infants, and the results obtained are summarized below. Serum concentrations of CAZ after administration of 20 mg/kg were satisfactorily high regardless of the route of administration; bolus intravenous injection or 1-hour intravenous drip infusion. Like other cephem antibiotics, half-lives tended to be shorter as day-ages of subject became higher. Although there were some differences in urinary recovery rates between different dosage groups, they were generally high. Clinical efficacy was either excellent or good in all 21 assessable cases. In 23 cases examined for adverse effects, diarrhea was observed in 1 case, and elevation of GOT and GPT, in another case.     

Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae

Background

Ceftazidime/avibactam is a newly approved β-lactam/β-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited.

A pharmacokinetic and clinical evaluation of ceftazidime in neonates and premature infants. A study of ceftazidime in the perinatal co-research group

Ceftazidime (CAZ) was evaluated for its pharmacokinetics and clinical usefulness in neonates and premature infants. The results obtained were summarized below. Following intravenous injection of CAZ 10 or 20 mg/kg to neonates and premature infants, dose response was observed in serum concentrations ranging from 5.1 to 21.9 micrograms/ml at 6 hours after the injection. The serum half-life tended to be longer in premature infants than in neonates; the half-life being longer for an infant with lower day-age. Urinary recovery rates during the first 6 hours after single administrations of 10 mg/kg of CAZ tended to be higher in neonates than in premature infants, and higher rates were observed in older infants. However, no noticeable difference was observed after the administration of CAZ 20 mg/kg. Clinical efficacy was evaluated in 99 neonates and 55 premature infants (156 infections), daily doses ranging from 21.1 to 246.4 mg/kg. Out of 105 cases of common infections, mainly 44 cases with causative organisms identified (including 17 of sepsis, 7 of pneumonia, 4 of purulent meningitis, 11 of urinary tract infections) were examined for the clinical efficacy. The efficacy of CAZ was excellent in 21, good in 18, fair in 1 and poor in 4, with the efficacy rate of 88.6%. In the remaining 61 cases, i.e., 37 with causative organisms unknown and 24 with signs of intrauterine infections, the efficacy rate was 95.1%. Other than these cases, additional 51 cases were given CAZ solely for prophylaxis of infections, and the results were found satisfactory. On the whole, clinical efficacy rate of CAZ was 94.9% in 156 cases. Out of the 44 cases examined for bacteriological responses, 38 were evaluated as 'eradicated', 3 'persisted' and 3 'unknown' with eradication rate of 92.7%. Replacement of organisms (superinfection) was observed in 3 cases. Out of 179 cases in which adverse effects were assessable, adverse effects were observed in a total of 4 cases (2.2%), i.e., 3 cases of diarrhea (1.7%) and 1 case of rash (0.6%), and abnormal laboratory findings were observed in a total of 14 cases (7.8%), i.e., increase in eosinophiles count in 8 (4.5%), elevation of GOT in 3 (1.7%), increase in platelet, elevation of GOT . GPT, and elevation of GOT . GPT . BUN in 1 case each (0.6%). None of them were severe and they were transient. Elevations of bilirubin and cases of positive PIVKA II associated with CAZ were not observed.(ABSTRACT TRUNCATED AT 400 WORDS)     

头孢他啶/阿维巴坦对耐碳青霉烯肠杆菌科细菌的体外抗菌活性研究

目的 头孢他啶/阿维巴坦(CAZ/AVI)是第三代头孢菌素和新型的非β-内酰胺酶类的β-内酰胺酶抑制剂阿维巴坦相 结合的抗生素,对多重耐药菌具有抗菌活性,本研究评价CAZ/AVI对临床分离耐碳青霉烯肠杆菌科细菌(carbapenem-resistant Enterobacteriaceae,CRE)的体外抗菌活性,同时评价CAZ/AVI对不同菌属的CRE菌和携带不同耐药基因型的CRE菌的体外抗菌 活性。方法 对收集来自解放军302医院和宁夏医科大学总医院2008年1月至2017年12月临床分离的266株CRE菌株进行了最低抑 菌浓度(minimum bacteriostatic concentration, MIC)的测定;采用特异引物扩增法进行耐药基因型的测定,进一步分析CAZ/AVI对 携带不同耐药基因型的CRE菌的体外抗菌活性。结果 CAZ/AVI体对临床分离CRE菌的体外抑菌活性为49.62%,明显优于头孢 他啶和其他对照药物(P=0),但弱于多黏菌素B和替加环素(P=0.003);对克雷伯菌属CRE菌的体外抑菌效果明显,可达到63.75% 的体外活性抑菌率,其次为肠杆菌属CRE菌(23.81%),对埃希菌属CRE菌的体外抑菌率最低(13.33%);对于携带blaKPC-2 基因型 的CRE菌株体外抑菌率可达到69.23%,而对于携带blaNDM 和blaIMP 的基因型的CRE菌株作用相当(P=0.889),体外抑菌率分别为 2.22%和8.33%。结论 CAZ/AVI坦对CRE菌表现出了一定的体外抗菌活性优势,尤其是增强了头孢他啶的体外抗菌活性。对克 雷伯菌属CRE菌的体外抑菌活性明显,并且能够很好的抑制携带blaKPC-2 基因型的CRE菌。     

头孢他啶/阿维巴坦钠治疗肝移植术后CRKP感染的临床回顾性研究

摘要：目的 探讨头孢他啶/阿维巴坦钠治疗肝移植术后耐碳青霉烯肺炎克雷伯菌(CRKP)感染的临床疗效,为肝移植术 后患者抗感染治疗提供理论依据。方法 回顾性分析2019年8月—2020年3月肝移植术后确诊耐碳青霉烯类肺炎克雷伯菌感 染的11例患者临床资料。统计分析感染部位、肝移植手术时间、首次使用头孢他啶/阿维巴坦钠时间、平均用药时间、临床 转归以及不良反应。结果 肝移植术后CRKP感染部位主要为呼吸道、腹腔、血液和胆道,术后至首次用药平均间隔时间为 (275.27±364.30)d,中位时间96d,头孢他啶/阿维巴坦钠平均用药时间数为(24.0±12.3)d,中位时间24d。MDR-CRKP临床治愈 率83.33%,XDR-CRKP临床治愈率60.0%,不良反应较轻。结论 头孢他啶/阿维巴坦钠可用于治疗肝移植术后CRKP感染。     

头孢他啶/阿维巴坦与碳青霉烯类治疗复杂腹腔感染疗效和安全性的系统评价

目的 系统评价头孢他啶/阿维巴坦(ceftazidime/avibactam,CAZ/AVI)与碳青霉烯类治疗复杂腹腔感染的有效性和安全性,为其临床合理用药提供循证参考。方法 计算机检索PubMed、Embase、Ovid Medline、The Cochrane Library、中国期刊全文数据库、中文科技期刊数据库等,检索时限为各数据库建库起至2020年2月。纳入头孢他啶/阿维巴坦与碳青霉烯类比较治疗复杂腹腔感染的随机对照试验(RCT),对符合纳入标准的临床研究进行资料提取和评价偏倚风险后,采用Rev Man 5.3统计软件对结果进行分析。结果 共纳入4篇RCT,合计1729例患者。结果显示有效性方面：CAZ/AVI组临床治愈率和细菌清除率在mMITT人群中的TOC和EOT访视时分别优于碳青霉烯类组[OR=0.72, 95%CI(0.52, 0.99), P=0.04][OR=0.56, 95%CI(0.38, 0.82), P=0.003]、[OR=0.72, 95%CI(0.52, 0.99), P=0.04]和[OR=0.57, 95%CI(0.38, 0.84), P=0.005],差异均有统计学意义;在LFU访视时两组患者临床治愈率和细菌清除率相当,差异无统计学意义。两组患者在MITT、CE、ME和EME人群中的临床治愈率相当,差异无统计学意义。两组患者在ME、EME人群中的细菌清除率相当,差异无统计学意义。安全性方面：CAZ/AVI组患者的不良事件发生率、严重不良事件发生率和病死发生率高于碳青霉烯类,其中不良反应事件发生率结果[OR=1.24, 95%CI(1.02,1.51), P=0.03]差异有统计学意义,严重不良事件发生率和死亡率结果差异无统计学意义。结论 对于复杂腹腔感染,研究结果提示CAZ/AVI较碳青霉烯类在某些人群中可以显著提高临床疗效,大部分人群中两药疗效相当。CAZ/AVI可显著增加不良事件发生率,但并不增加严重不良事件发生率和死亡率。总的来说,在没有更多的RCT前,将CAZ/AVI作为碳青霉烯类的替代药物使用时,应考虑到较高的不良事件发生风险。