表征碳青霉烯类药物稳定性的指针性杂质的确定及其应用

目的:采用自身降解物质作为定量指标,表征碳青霉烯类药物的降解程度,用以考察此类药物的稳定性和指针性杂质共性。方法:以美罗培南、亚胺培南和比阿培南为例,进行加速稳定性试验,寻找具有代表性的指针性杂质,并考察药物自身降解程度与指针性杂质之间的量值关系,用以作为稳定性表征指标。结果:HPLC法分析得到的美罗培南、亚胺培南和比阿培南主成分含量降低1.0%时的警戒线分别为:187,261,84。通过LC-MS确证指针性杂质结构为开环水解物。结论:通过对碳青霉烯类药物稳定性考察,依据指针性杂质表征降解程度。     

中国肺炎克雷伯菌碳青霉烯类抗生素耐药现状和流行病学分析

目的研究中国肺炎克雷伯菌对碳青霉烯类抗生素的耐药性及碳青霉烯酶在肺炎克雷伯菌中的分布。方法采用琼脂稀释法进行药敏实验;用PCR扩增和测序检测携带碳青霉烯酶基因的菌株;通过改良霍奇试验(MHT)和亚胺培南/EDTA双纸片协同试验(DDST)进行产碳青霉烯酶表型检测;利用PFGE及MLST对产酶菌株做流行病学分析。结果与结论产碳青霉烯酶肺炎克雷伯菌的亚胺培南MIC处于较低水平;KPC-2和IMP-4为本研究发现的主要酶型;肺炎克雷伯菌IMP的遗传背景较为复杂。     

(S)-1-(N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷的合成

目的 合成帕尼培南关键中间体 (S)-1-( N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷。方法 以氯甲酸烯丙酯为酰化剂,与盐酸乙脒进行 N-酰化反应得到 1-亚胺乙基氨基甲酸烯丙酯,该化合物与 3-R-羟基吡咯烷进行缩合,再经甲磺酰化、S_N2 取代、水解共 5 步反应得到目标化合物。结果与结论 该合成路线中使用新型保护基烯丙氧羰基替代传统的保护基—对硝基苄氧羰基,目标化合物的结构经 ¹H-NMR、MS 谱确证,总收率为 41.6%,各步反应操作简便,条件温和,有利于工业化生产。     

3-羧酸碳青霉烯和硫霉素的生物合成研究进展

3-羧酸碳青霉烯和硫霉素均属β-内酰胺类抗生素,具有重要的临床应用价值.讨论3-羧酸碳青霉烯和硫霉素的生物合成途径和影响因素,并介绍一些相关的新化合物,旨在为改进该类抗生素的发酵条件及利用组合生物合成技术创制新药提供参考和思路.     

耐碳青霉烯类肺炎克雷伯菌耐药基因检测及同源性

目的探讨耐碳青霉烯类肺炎克雷伯菌(CRKP)耐药基因型及同源性。方法收集某院2015年9月—2016年2月临床标本分离的38株CRKP,采用聚合酶链反应(PCR)方法检测耐药基因型,脉冲场凝胶电泳(PFGE)分析菌株同源性。结果 38株CRKP主要来源于重症监护病房(ICU)及外科重症监护病房(SICU),分别占39.48%、34.21%。38株CRKP均检出blaKPC和blaSHV耐药基因,6株检出blaCTX耐药基因。PFGE显示共分成A、B、C、D4个谱型,其中以C型为主(65.78%,25/38)。A型菌株中菌株14、15、16携带blaKPC-2型、blaSHV型、blaCTX-M-15耐药基因,此3株细菌均是SICU患者分离的,菌株14和15分离自同一天,菌株16分离时间延后一周;C型菌株中,菌株10、18、25、28的同源性为100%,菌株10、18分离自ICU患者,菌株25、28分离自神经内一科患者(均从ICU转出),均是在ICU住院期间检出,且分离时间相差1 d。结论该院CRKP耐药基因型以blaKPC及blaSHV为主,存在克隆株医院内流行。     

Carbapenem-resistant Acinetobacter baumannii: epidemiology,surveillance and management

Carbapenem-resistant Acinetobacter baumannii pose a significant threat to hospitalized patients, as therapeutic options are scarse. Alarmingly, rates of carbapenem-resistance in A. baumannii are on the rise and are slowly becoming a routine phenotype for this organism. This review focuses on infection control strategies for identification and control of A. baumannii, as well the available therapeutic options.     

Ertapenem: review of a new carbapenem

The carbapenems are β-lactam-type antibiotics with an exceptionally broad spectrum of activity. Ertapenem is a new carbapenem developed to address the pharmacokinetic shortcomings (short half-life) of imipenem and meropenem. Ertapenem shares similar structural features with meropenem, including its stability to dehydropeptidase-1, allowing it to be administered without a dehydropeptidase-1 inhibitor. Ertapenem, like imipenem and meropenem, demonstrates broad-spectrum antimicrobial activity against many Gram-positive and -negative aerobes and anaerobes and is resistant to nearly all β-lactamases, including extended-spectrum β-lactamases and AmpCs. However, it differs from both imipenem and meropenem in demonstrating limited activity against Enterococcus spp., Pseudomonas aeruginosa and other nonfermentative Gram-negative bacteria commonly associated with nosocomial infections. The extensive protein binding of ertapenem extends the half-life and allows for once-daily dosing. Prospective, multicenter, randomized, double-blind, comparative clinical studies demonstrate similar clinical efficacy of ertapenem compared with other agents. Clinical trials of complicated intra-abdominal infection, acute pelvic infection, complicated skin and soft-structure infection, community-acquired pneumonia and complicated urinary tract infections demonstrated that ertapenem has equivalent efficacy and safety compared with ceftriaxone and piperacillin/tazobactam. Ertapenem is a promising new carbapenem with excellent efficacy and safety for the treatment of a variety of community-acquired infections. It also appears to be of great value as an outpatient parenteral antimicrobial therapy.     

Carbapenem-resistant Gram-negative bacteria: how to prioritize infection prevention and control interventions in resource-limited settings?

Emergences of carbapenem-resistant Gram-negative bacteria (CRGNB) have heightened global awareness of the prioritization of infection prevention and control (IPC) interventions to minimize infections attributed to these bacteria. Effective new antibiotic drugs for CRGNB are estimated to be at least 5 years off completion of trials and approval for use. Hence, effective IPC strategies remain at the core of clinical care and research for patients with CRGNB infection. The authors summarize current evidence and viewpoints for IPC strategies as related to the emergence, transmission and prevention of CRGNB.