美罗培南的体外抗菌活性研究

目的 评价国产美罗培南对产β-内酰胺酶细菌的体外抗菌活性。方法 琼脂稀释法测定美罗培南对110株产β-内酰胺酶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 碳青霉烯类抗生素对产β-内酰胺酶菌株具有高度抗菌活性，国产美罗培南作用略强于亚胺培南。碳青霉烯类抗生素体外抗菌作用优于头霉素、第四代头孢菌素、β-内酰胺类抗生素与β-内酰胺酶抑制剂合剂、喹诺酮类和氨基糖苷类药物。结论 国产美罗培南是治疗产β-内酰胺酶细菌所致感染的理想药物。     

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。     

青霉烯类及碳青霉烯类抗生素的结构特点与分级管理建议

目的:为抗菌药物的临床分级管理提供建议,促进青霉烯类和碳青霉烯类抗生素的合理使用.方法:检索国内外文献,对已经上市的青霉烯类和碳青霉烯类抗生素的结构、药理学和药动学特性、抗菌谱及临床应用等进行阐述,分析和比较不同品种的特点,提出分级管理建议.结果 和结论:厄他培南具有半衰期长、对产超广谱β-内酰胺酶(ESBLs)肠杆菌...     

青霉烯类抗生素的研究进展

青霉烯类抗生素首次于1975年由R.Bwood ward等基于青霉素与头孢菌素融合的概念,向青霉素骨架中引入双键,以增大β-内酰胺反应性,从而提高抗菌活性的设想而设计合成的,青霉烯类抗生素抗菌谱广、抗菌活性强,对β-内酰胺酶产生菌,柠檬酸杆菌,肠球菌与厌氧菌也有良好作用,青霉烯类化合物也具有广泛的抗菌活性,同时对脱氢肽水解酶-I(DAP-I)较碳青霉烯稳定,但抗绿脓杆菌活性低于碳青霉烯。青霉烯类抗生素的化学性质不如碳青霉烯稳定,     

亚胺培南、帕尼培南、美罗培南的临床应用评价

碳青霉烯是一组新型β-内酰胺类抗生素 ,对革兰阳性菌(Ｇ )和革兰阴性菌 (Ｇ - )、需氧菌、厌氧菌都有很强的抗菌活性。该类抗生素具有抗菌谱广 ,抗菌活性强 ,对β-内酰胺酶稳定以及毒性低等特点。目前 ,该类抗生素在临床用得较多的品种主要有亚胺培南、帕尼培南、美罗培南。     

碳青霉烯类抗生素多尼培南的体外抗菌活性

多尼培南是新的注射用碳青霉烯类广谱抗生素。它是1β-甲基碳青霉烯，由日本大阪的Shionogi等最先发现。该药目前在美国进行临床试验研究。Yigong等测定了多尼培南对临床分离株的体外抗菌活性，并与其他几种碳青霉烯类抗生素(厄他培南、亚胺培南、美罗培南)、头孢菌素(头孢吡肟、头孢曲松)和哌拉西林／三唑巴坦对381株革兰阴性菌和434株革兰阳性菌进行了体外抗菌活性比较。     

青霉烯及其代表药物法罗培南的研究进展

青霉烯是一类非典型的β-内酰胺类抗生素。与其它的β-内酰胺类抗生素包括碳青霉烯类相比,其结构明显不同。因其具有广谱的抗菌活性,对β-内酰胺酶的高度稳定性,对青霉素结合蛋白的高亲和力等主要特点,而受到广泛关注。其代表药物法罗培南是第一个开发上市的青霉烯类抗生素,对需氧及厌氧性革兰阳性菌、革兰阴性菌均显示出广谱的抗菌活性,是一类新的抗感染药物。对青霉烯类抗生素的结构特点、作用机制、体内外研究等进行综述。     

碳青霉烯类抗生素艾他培南的药理研究及其临床应用

艾他培南是新型广谱长效碳青霉烯类抗生素,抗菌活性强,对绝大多数β-内酰胺酶稳定。可用于成人复杂性腹腔感染、社会获得性肺炎、复杂性皮肤及皮肤软组织感染和尿路感染等。     

厄他培南致谵妄症状3例并文献复习

<正>厄他培南(ertapenem)是广谱碳青霉烯类抗生素,属于不典型β-内酰胺类抗生素,对于革兰阳性、阴性及厌氧菌有显著抗菌活性^([1,2]),且耐β-内酰胺酶,可用于治疗严重感染。很多研究([1,2]),且耐β-内酰胺酶,可用于治疗严重感染。很多研究^([3,4])报道了其治疗社区获得性肺炎具有很高的有效性及安全性。本文对厄他培南所致精神症状病例进行     

美罗培南在国内外临床指南中的推荐

美罗培南为人工合成的广谱碳青霉烯类抗生素,该药易穿透大多数革兰阳性菌、阴性菌的细胞壁,通过抑制细菌细胞壁的合成而产生抗菌作用。除金属β-内酰胺酶以外,美罗培南对大多数β-内酰胺酶的水解作用具有较强的稳定性。由于美罗培南对多重耐药的革兰阴性杆菌均表现出较好的抗菌效果,各科指南也纷纷推荐该药用于相应感染的治疗。查阅了10余篇与美罗培南相关的抗感染治疗指南,归纳后主要有以下几类。     

Recent developments in carbapenems

Carbapenems are β-lactam antibiotics characterised by the presence of a β-lactam ring with a carbon instead of sulfone in the 4-position of the thyazolidinic moiety. The first carbapenem to be utilised in therapy was imipenem, the N-formimidoyl derivative of thienamycin. Imipenem is coadministered with cilastatin, an inhibitor of human renal dehydropeptidase I, as imipenem is hydrolysed by this enzyme. Meropenem was the first carbapenem with a 1-β-methyl group and 2-thio pyrrolidinyl moiety, which renders this antibiotic stable to renal dehydropeptidase I. Other carbapenems for parenteral administration later discovered include biapenem, panipenem, ertapenem, lenapenem, E-1010, S-4661 and BMS-181139. Carbapenems which are orally administered include sanfetrinem, DZ-2640, CS-834 and GV-129606. Carbapenems have an ultra-broad spectrum of antibacterial activity and stability to almost all clinically relevant β-lactamases. This differentiates them from all other currently available classes of β-lactam antibiotics. However, Class B β-lactamases, along with some rare Class A and D enzymes, are able to hydrolyse these antibiotics. Although Class B enzymes are generally chromosomally-encoded (isolated from Stenotrophomonas maltophilia, Aeromonas spp., Bacillus cereus, Bacteroides fragilis, Flavobacterium spp. and Legionella gormanii), plasmid-metallo-β-lactamases now are appearing in B. fragilis, Pseudomonas aeruginosa, Acinetobacter baumannii and members of Enterobacteriaceae such as Serratia marcescens and Klebsiella pneumoniae. The number of these enzymes compared to the number of other β-lactamase types is still low, however, it is likely that they will spread due to the increased selective pressure of carbapenem use. The very broad spectrum of antimicrobial activity associated with a good clinical efficacy and a favourable safety profile makes the carbapenems valuable as ‘first-line’ antibiotics in initial empirical therapy for the treatment of severe infections.     

Carbapenems in pediatrics

Antimicrobial resistance is increasing among bacterial pathogens. In particular, organisms producing extended spectrum beta-lactamase enzymes (ESBLs) and AmpC chromosomal beta-lactamase enzymes are resistant to third generation cephalosporins and pose a formidable challenge in the management of seriously ill patients. Carbapenems are a class of broad-spectrum antibiotics with stability against ESBL and AmpC chromosomal beta-lactamases. They are well tolerated by patients. This review will examine the pharmacokinetic and pharmacodynamic properties of two carbapenems imipenem and meropenem and discuss their clinical use in children. References are limited to the English language and extend back to 1980. Sources include computerized databases such as MEDLINE searched using PubMed, and bibliographies of recent articles and books. Approximately 50% of the articles initially reviewed are included in the bibliography. Carbapenems are efficacious in the treatment of a variety of bacterial infections including meningitis, pneumonia, intraabdominal infections, bone, joint and urinary tract infections. The broad spectrum activity and comparatively low toxicity of carbapenems make them valuable therapeutic agents in the treatment of seriously ill patients with bacterial infections. These agents should be used judiciously in order to minimize the risk for development of carbapenem-resistant pathogens.     

Treatment options for extended-spectrum beta-lactamase (ESBL) and AmpC-producing bacteria

Introduction: Extended spectrum β-lactamases (ESBL) and AmpC β-lactamases are increasing causes of resistance in many Gram-negative pathogens of common infections. This has led to a growing utilization of broad spectrum antibiotics, most predominately the carbapenem agents. As the prevalence of ESBL and AmpC-producing isolates and carbapenem resistance has increased, interest in effective alternatives for the management of these infections has also developed.

Areas covered: This article summarizes clinical literature evaluating the utility of carbapenem-sparing regimens for the treatment of ESBL and AmpC-producing Enterobacteriaceae, mainly β-lactam-β-lactamase inhibitor combinations and cefepime (FEP).

Expert opinion: Based on available data, the use of piperacillin-tazobactam (PTZ) and FEP in the treatment of ESBL-producing Enterobacteriaceae cannot be widely recommended. However, certain infections and patient characteristics may support for effective use of these alternative agents. In the treatment of infections caused by AmpC-producing Enterobacteriaceae, FEP has been shown to be a clinically useful carbapenem-sparing alternative. Carbapenems and FEP share many structurally similar characteristics in regards to susceptibility to AmpC β-lactamases, which further create confidence in the use FEP in these situations. Patient and infection specific characteristics should be used to employ FEP optimally.     

Comparative review of the carbapenems

The carbapenems are beta-lactam antimicrobial agents with an exceptionally broad spectrum of activity. Older carbapenems, such as imipenem, were often susceptible to degradation by the enzyme dehydropeptidase-1 (DHP-1) located in renal tubules and required co-administration with a DHP-1 inhibitor such as cilastatin. Later additions to the class such as meropenem, ertapenem and doripenem demonstrated increased stability to DHP-1 and are administered without a DHP-1 inhibitor. Like all beta-lactam antimicrobial agents, carbapenems act by inhibiting bacterial cell wall synthesis by binding to and inactivating penicillin-binding proteins (PBPs). Carbapenems are stable to most beta-lactamases including AmpC beta-lactamases and extended-spectrum beta-lactamases. Resistance to carbapenems develops when bacteria acquire or develop structural changes within their PBPs, when they acquire metallo-beta-lactamases that are capable of rapidly degrading carbapenems, or when changes in membrane permeability arise as a result of loss of specific outer membrane porins. Carbapenems (imipenem, meropenem, doripenem) possess broad-spectrum in vitro activity, which includes activity against many Gram-positive, Gram-negative and anaerobic bacteria; carbapenems lack activity against Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. Compared with imipenem, meropenem and doripenem, the spectrum of activity of ertapenem is more limited primarily because it lacks activity against Pseudomonas aeruginosa and Enterococcus spp. Imipenem, meropenem and doripenem have in vivo half lives of approximately 1 hour, while ertapenem has a half-life of approximately 4 hours making it suitable for once-daily administration. As with other beta-lactam antimicrobial agents, the most important pharmacodynamic parameter predicting in vivo efficacy is the time that the plasma drug concentration is maintained above the minimum inhibitory concentration (T>MIC). Imipenem/cilastatin and meropenem have been studied in comparative clinical trials establishing their efficacy in the treatment of a variety of infections including complicated intra-abdominal infections, skin and skin structure infections, community-acquired pneumonia, nosocomial pneumonia, complicated urinary tract infections, meningitis (meropenem only) and febrile neutropenia. The current role for imipenem/cilastatin and meropenem in therapy remains for use in moderate to severe nosocomial and polymicrobial infections. The unique antimicrobial spectrum and pharmacokinetic properties of ertapenem make it more suited to treatment of community-acquired infections and outpatient intravenous antimicrobial therapy than for the treatment of nosocomial infections. Doripenem is a promising new carbapenem with similar properties to those of meropenem, although it appears to have more potent in vitro activity against P. aeruginosa than meropenem. Clinical trials are required to establish the efficacy and safety of doripenem in moderate to severe infections, including nosocomial infections.     

肺炎克雷伯菌对碳青霉烯类抗菌药物的主要耐药机制及治疗策略

肺炎克雷伯菌(Klebsiella pneumoniae,Kpn)是临床常见的条件致病菌。碳青霉烯类药物抗菌活性强,对各种类型的β-内酰胺酶高度稳定,是治疗Kpn感染的最佳抗菌药物。然而,随着碳青霉烯类抗菌药物的使用,对碳青霉烯耐药Kpn(Carbapenem-resistant Klebsiella pneumoniae,CR-Kp)在临床的分离率逐年升高。CR-Kp感染治疗可供选择的抗菌药物非常有限,这给临床治疗带来很大挑战。本文主要从碳青霉烯酶的产生、细胞膜孔道蛋白缺失或者数量不足两个方面对CR-Kp的耐药机制以及治疗进展做一综述。     

Recent developments in carbapenems

Carbapenems are beta-lactam antibiotics characterised by the presence of a beta-lactam ring with a carbon instead of sulfone in the 4-position of the thyazolidinic moiety. The first carbapenem to be utilised in therapy was imipenem, the N-formimidoyl derivative of thienamycin. Imipenem is coadministered with cilastatin, an inhibitor of human renal dehydropeptidase I, as imipenem is hydrolysed by this enzyme. Meropenem was the first carbapenem with a 1-beta-methyl group and 2-thio pyrrolidinyl moiety, which renders this antibiotic stable to renal dehydropeptidase I. Other carbapenems for parenteral administration later discovered include biapenem, panipenem, ertapenem, lenapenem, E-1010, S-4661 and BMS-181139. Carbapenems which are orally administered include sanfetrinem, DZ-2640, CS-834 and GV-129606. Carbapenems have an ultra-broad spectrum of antibacterial activity and stability to almost all clinically relevant beta-lactamases. This differentiates them from all other currently available classes of beta-lactam antibiotics. However, Class B beta-lactamases, along with some rare Class A and D enzymes, are able to hydrolyse these antibiotics. Although Class B enzymes are generally chromosomally-encoded (isolated from Stenotrophomonas maltophilia, Aeromonas spp., Bacillus cereus, Bacteroides fragilis, Flavobacterium spp. and Legionella gormanii), plasmid-metallo-beta-lactamases now are appearing in B. fragilis, Pseudomonas aeruginosa, Acinetobacter baumannii and members of Enterobacteriaceae such as Serratia marcescens and Klebsiella pneumoniae. The number of these enzymes compared to the number of other beta-lactamase types is still low, however, it is likely that they will spread due to the increased selective pressure of carbapenem use. The very broad spectrum of antimicrobial activity associated with a good clinical efficacy and a favourable safety profile makes the carbapenems valuable as 'first-line' antibiotics in initial empirical therapy for the treatment of severe infections.     

Multidrug-resistant Gram-negative bacterial infections: the emerging threat and potential novel treatment options

Gram-negative bacterial infections constitute an emerging threat because of the development of multidrug-resistant organisms. There is a relative shortage of new drugs in the antimicrobial development pipeline that have been tested in vitro and evaluated in clinical studies. Antibiotics that are in the pipeline for the treatment of serious Gram-negative bacterial infections include the cephalosporins, ceftobiprole, ceftarolin and FR-264205. Tigecycline is the first drug approved from a new class of antibiotics called glycylcyclines, and there has been renewed interest in this drug for the treatment of some multidrug-resistant Gram-negative organisms. Carbapenems in the pipeline include tomopenem, with the approved drugs doripenem and faropenem, an oral agent, under evaluation for activity against multidrug-resistant Gram-negative bacterial infections. Polymyxins are old antibiotics traditionally considered to be toxic, but which are being used because of their activity against resistant Gram-negative organisms. New pharmacokinetic and pharmacodynamic data are available regarding the use of these agents. Finally, antimicrobial peptides and efflux pump inhibitors are two new classes of agents under development. This review of investigational antibiotics shows that several new agents will become available in the coming years, even though the pace of antimicrobial research is far from ideal.     

β-内酰胺酶抑制剂的研究和开发

β-内酰胺酶抑制剂对各种革兰阳性菌、革兰阴性菌、厌氧菌等所产生的β-内酰胺酶均有广泛的抑制作用,临床研究确认其与β-内酰胺类抗生素的复合制剂用于呼吸系统、腹腔、皮肤和软组织等感染的经验治疗有效,用于中性粒细胞减少的发热、院内感染也有效。β-内酰胺类抗生素/β-内酰胺酶抑制剂复合制剂治疗混合感染特别有效,用于多重耐药菌如不动杆菌属和嗜麦芽窄食单胞菌所致感染治疗亦在增加。本文简要介绍β-内酰胺酶抑制剂的发展和开发近况。     

产超广谱 β-内酰胺酶肠杆菌科细菌的感染与控制

超广谱β-内酰胺酶(ESBL)在肠杆菌科细菌中很常见,可水解超广谱头孢菌素,克拉维酸可抑制其水解作用。最主要的产ESBL的肠杆菌科细菌包括大肠杆菌、克雷伯菌属及变形杆菌属,在社区获得性感染中多见,也可见于医院获得性感染。近年来,产CTX-M型菌株明显增加,且逐渐超过SHV型及TEM型,成为目前最常见的β-内酰胺酶肠杆菌科细菌。出现产ESBL细菌感染的患者多合并相关的危险因素,如总住院时间长,ICU住院时间长,疾病严重,留置各种导管,接受肾脏替代治疗或机械通气等。防止患者之间传播对ESBL控制至关重要。正确的经验性抗生素对于治疗产ESBL细菌引起的感染非常重要。一旦ESBL阳性,即使体外药敏结果敏感,亦需慎用头孢菌素,此时应首选碳青霉烯类抗生素。     

The proper use of carbapenem examined by Monte Carlo simulation

Monte Carlo simulation was employed for this comparative study to determine the optimal Carbapenem and its dosing strategy to cure the infections by Escherichia coli and Pseudomonas aeruginosa and to consider how the difference of each Carbapenems in dosing regimens and antibiotic activity influenced to maximize % T > MIC. This result revealed that it was important to increase a dose and a number of doses a day, in addition to great antibiotic activity for maximizing % T > MIC.