碳青霉烯类抗生素临床应用与评价

目的：评价碳青霉烯类抗生素临床应用概况。方法：收集国内外相关文献,从碳青霉烯类抗生素应用状况、有效性、安全性等方面进行分析评价。结果及结论：碳青霉烯类抗生素目前已普遍应用于临床。     

碳青霉烯类抗生素的主要品种和临床选用

碳青霉烯类是20世纪80年代开始发展的一组新型广谱的β—内酰胺类抗生素，用于临床不过十余年，对控制耐药菌、产酶菌感染和免疫缺陷者感染，发挥了极其重要的作用。然而，对其临床适应证的定位还存在一些分歧，值得深入讨论，以保证该类药物长时期保持良好的临床疗效。     

碳青霉烯类抗生素的研究进展

目的：促进临床对碳青霉烯类抗生素的合理应用。方法：参考国内外文献,对7种碳青霉烯类抗生素的构效特点、药理特点、临床应用等进行阐述,分析比较7个品种之间的不同特点。结果：本类抗生素具有抗菌谱广、抗菌活性强和对β-内酰胺酶高度稳定的特点,经临床验证其疗效确切。结论：碳青霉烯类抗生素是临床治疗严重的混合性感染和对付耐药菌株的有力武器。     

碳青霉烯类抗生素的研究进展及其在抗感染中的应用评价

目的:介绍碳青霉烯类抗生素进展及其临床评价.方法:采用近期国内、外相关文献进行综述.结果与结论:近年来,碳青霉烯抗生素进展十分迅速,其抗菌谱极广,杀菌活性超过头孢菌素,尤以对抗铜绿假单胞菌和耐甲氧西林金葡球菌的活性最为突出;其次,碳青霉烯类抗生素对细菌靶体蛋白、青霉素结合蛋白有良好的选择性毒性,已成为目前有关抗生素研究和开发的重要领域.     

碳青霉烯类抗生素国内外开发现状与前景分析

碳青霉烯类抗生素是迄今为止抗感染药物中抗菌谱最广、抗菌活性最强的“非典型性”B内酰胺类抗生素。碳青霉烯的化学结构不同于青霉素／头孢菌素类抗生素之处在于其母环的2位上多了一个双键,4位上的硫原子被碳原子所取代。     

新的碳青霉烯类抗生素

碳青霉烯类抗生素为以碳青霉烯为母核的β-内酰胺类抗生素,亚胺培南(imipenem)为该类药物目前临床已应用的品种。在临床应用的所有β-内酰胺类药物中,其抗菌谱最广,对包括许多耐药菌株在内的革兰阳性、阴性需氧及厌氧菌均具良好抗菌活性;不仅对丝氨酸β-内酰胺酶稳定性强,而且又是该类酶的有效抑制剂。然而,亚胺培南却具以下不足:1)对肾脏上皮细胞分泌的脱氢肽酶的灭活作用较敏感,因此需与该酶抑制剂西司他     

碳青霉烯与青霉烯类抗生素研究开发的进展

自1929年发现青霉素至今,已半个多世纪,青霉素与头孢菌素等β-内酰胺类抗生素在医疗中发挥了重要作用。近二十余年来相继发现一些主核结构不同于传统的青霉烷与头孢烯的抗生素,如氧青霉烷、青霉烯、碳青霉烯、氧头孢烯、碳头孢烯、单环β-内酰胺等类化合物,为非典型β-内酰胺类抗生素,其中碳青霉烯与青霉烯类的抗菌性能更具特色,优异品种不断涌现,已成为化疗药物中不可忽视的一支新生力量。 1 碳青霉烯类抗生素 1976年发现链霉素菌(strptomyces cattleya)产生的硫霉素(thienamycin),是第一个碳青霉烯,迅即发现多种链霉菌产生此类化合物。根据5,6位的立体化学,分为顺、     

碳青霉烯类抗生素的研究进展

碳青霉烯类抗生素由于与青霉素类和头孢菌素类抗生素骨絮结构上的区别，具有能有效穿透细胞、对多种β-内酰胺酶稳定及抗菌谱广泛的特点。本文介绍已上市或正在研究阶段的非胃肠途径给药的碳青霉烯类抗生素(亚胺培南、帕尼培南、美洛培南、比阿培南、羟丙胺培南、MK-826、S-4661、ER-35786)和可口服的品种(SC-834，DZ-2640，OAC-983)的化学结构、抗菌活性、作用机制及耐药性方面的情况。     

碳青霉烯类抗生素结构特征及其抗菌作用

碳青霉烯类抗生素是由青霉素通过结构改造而成的一类新型抗生素,在治疗疾病中显示出毒性低、疗效显著的特点.第一个碳青霉烯类抗生素是通过在天然物质中寻找而于1976年发现的.经过对其结构和抗菌活性及药理作用的深入研究,目前已有第2代碳青霉烯类抗生素在临床上使用,更多的碳青霉烯类抗生素正在研究中.     

碳青霉烯类抗生素的研究进展

目的综述非经典β-内酰胺类抗生素中碳青霉烯类抗生素的药理活性研究进展以及市场前景。方法根据国内外有代表性的19篇文献,对相关内容进行分析、归纳、整理。结果碳青霉烯类抗生素与经典青霉烯的结构相比,除4位硫原子被碳代替外,还存在6位反式羟乙基侧链,此特殊结构,使得这类抗生素成为非典型超广谱的β-内酰胺抗生素,并对β-内酰胺酶有耐受和抑制作用,成为治疗重症感染的一线药物,广泛应用于临床。此类药物存在半衰期短、口服品种少等缺陷,有待进一步开发新品种。结论碳青霉烯类抗生素由于其结构的特殊性,因而相对于其他抗生素具有较强的抗菌性能,已成为目前有关抗生素研究和开发的重要领域,具有广阔的市场前景。     

临床药师干预提升碳青霉烯类抗菌药物合理使用效果分析

目的探析临床药师干预碳青霉烯类抗菌药物合理使用效果。方法采用安徽省儿童医院美康临床药学管理系统生成随机数的方法随机抽取 2017年 8—12月(干预前)与 2018年 8—12月(干预后)使用碳青霉烯类抗菌药物的住院病例各 100例,进行合理性分析。结果临床药师干预后,该院碳青霉烯类抗菌药物使用评价得分由( 74.45±7.26)分升高到( 94.70±5.31)分;适应证合理率由 86%提高到 98%;品种选择合理率由 87%提高到 99%;单次剂量、溶液及配伍合理率由 65%提高到 98%;药敏送检率由 78%提高到 95%;申请会诊单由 72%提高到 100%;出院病儿碳青霉烯类抗菌药物使用强度由干预前( 3.96±0.86) DDDs·(100人) -1·d-1降到( 2.27±0.72)DDDs·(100人) -1·d-1。均差异有统计学意义( P＜0.05)。结论临床药师干预显著提高碳青霉烯类抗菌药物合理使用率,规范临床碳青霉烯类抗菌药物的应用情况,进一步促进临床合理用药。     

A review of the carbapenems in clinical use and clinical trials

Despite alarming data showing the ever increasing number of bacteria becoming resistant to different classes of antibiotics through various mechanisms, the carbapenems remain a unique class of antibiotics that possess the broadest spectrum against Gram-positive, Gram-negative, aerobic and anaerobic organisms. However, bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, carry mechanisms that can inactivate the carbapenems. This article gives a review of the carbapenems that are currently in clinical use as well as discusses the new carbapenems that are in clinical trials. These new carbapenems show promising potential to overcome the resistance against the presently existing carbapenems. The present article shows the recent patents using carbapenems as an effective antibiotic.     

Comparative pharmacokinetics of the carbapenems: clinical implications

During the last few decades, several carbapenems have been developed. The major characteristic of the newer drugs, such as MK-826, is a prolonged half-life. Alternatively, some carbapenems have been developed that can be given orally, such as CS-834 and L-084. Although imipenem and panipenem have to be administered with a co-drug to prevent degradation by the enzyme dehydropeptidase-1 and reduce nephrotoxicity, the newer drugs such as meropenem, biapenem and lenapenem are relatively stable towards that enzyme. Structural modifications have, besides changes in pharmacology, also led to varying antimicrobial properties. For instance, meropenem is relatively more active against Gram-negative organisms than most other carbapenems, but is slightly less active against Gram-positive organisms. Except for half-life and bioavailability, the pharmacokinetic properties of the carbapenems are relatively similar. Distribution is mainly in extracellular body-water, as observed both from the volumes of distribution and from blister studies. Some carbapenems have a better penetration in cerebrospinal fluid than others. In patients with renal dysfunction, doses have to be adjusted, and special care must be taken with imipenem/cilastatin and panipenem/betamipron to prevent accumulation of the co-drugs, as the pharmacokinetic properties of the co-drugs differ from those of the drugs themselves. However, toxicity of the co-drugs has not been shown. The carbapenems differ in proconvulsive activity. Imipenem shows relatively the highest proconvulsive activity, especially at higher concentrations. Pharmacodynamic studies have shown that the major surrogate parameter for antimicrobial efficacy is the percentage of time of the dosage interval above the minimum inhibitory concentration (MIC). The minimum percentage percentage of time above the MIC (TaM) needed for optimal effect is known in animals (30 to 50%), but not in humans. It is probably less than 100%, but may be higher than 50%. Dosage regimens currently in use result in a TaM of about 50% at 4 mg/L, which is the current 'susceptible' breakpoint determined by the National Committee for Clinical Laboratory Standards (NCCLS) for most micro-organisms. Dosage regimens in patients with reduced renal clearance should be based on the TaM. The increased half-life of the newer carbapenems will probably lead to less frequent administration, although continuous infusion may still be the optimal mode of administration for these drugs. The availability of oral carbapenems will have a profound effect on the use of carbapenems in the community.     

In vitro antibacterial activities of carbapenems against clinical isolates

Antibacterial activities of four carbapenems, imipenem, panipenem, meropenem, and biapenem, were determined using 353 strains belonging to 18 bacterial species which were isolated from clinical materials at Ehime University Hospital. The MIC values of these carbapenems against MRSA were widely distributed between 0.1 and 100 micrograms/ml, and MIC90 values of these 4 carbapenems were 25-50 micrograms/ml. Any of these carbapenems prevented the bacterial growth of enterobacteriaceae of 8 bacterial species excluding S. macrescens at concentrations of 1 microgram/ml or less. The MIC values against P. aeruginosa showed relatively wide distribution, being 0.39-25 micrograms/ml for imipenem, 0.2-25 micrograms/ml for panipenem, 0.1-12.5 micrograms/ml for meropenem, and 0.2-12.5 micrograms/ml for biapenem. From those results, it was confirmed that any of the carbapenems tested had a wide antibacterial spectrum and strong antibacterial activities.     

Cephalosporins to carbapenems: 1-oxygenated carbapenems and carbapenams

The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corresponding carbapenem. The resulting 1-oxocarbapenems (2) were selectively transformed through reduction into 1-oxygenated carbapenems and carbapenams (3 and 4, respectively). On microbiological screening, a carbapenem (3c) was found to possess a broad spectrum of activity. An interesting antibacterial profile was discovered for a carbapenam (26).     

Validity of using imipenem as a representative carbapenems and levofloxacin as a representative fluoroquinolones in antibiotics susceptibility test for enterobacteriaceae

In antimicrobial susceptibility test for enterobacteriaceae, the efficacies of carpapenems are predicted by the minimum inhibitory concentration (MIC) of imipenem, and that of fluoroquinolones are predicted by the MIC of levofloxacin. To assess its judgement, we compared the MICs of imipenem, meropenem, panipenem, and doripenem for carbapenems, and ciprofloxacin, levofloxacin, tosufloxacin and pazufloxacin for fluoroquinolones of clinically isolated enterobacteria, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Serratia marcescens, Enterobacter cloacae and Citrobacterfreundii, those resistant to the third generation cephalosporin. MIC distributions in low concentration range are estranged in some strains, conspicuously S. marcescens, E. cloacae and C. freundii: meropenem and doripenem displayed low MIC value than imipenem and panipenem. Since the estrangements are appeared MIC value of less than 8 microg/ml, the interpretive results (susceptible, intermediate, resistant) are not affected. In fluoroquinolones, all 4 agents showed almost identical MIC distributions, thus the MIC of levofloxacin is accepted to use the reference for other fluoroquinolones. The existence of the strains harboring carbapenem-resistant gene displaying low MIC value of carbapenems was reported. For the sensitive detection of the candidate of carbapenem-resistant strains, cut-off value of each carbapenem should be reconsidered, and also other phonotype analysis should be applied. Genomic analysis also would be required to detect the carbapenem-resistant gene.     

Dual-action penems and carbapenems.

Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety. Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action.     

头孢类抗生素的临床应用

头孢菌素类与青霉素类同属β－内酰胺类抗生素，现就其抗菌机制、特点及临床应用、发展情况综合如下。１ 头孢类抗生素的作用机制、特点及发展 头孢菌素类和青霉素的母核不同，但同属于β－内酰胺类抗生素，均是通过干扰细菌细胞壁合成，加速细胞壁破坏而起杀菌作用。头孢类的特点是广谱、高效，对各种细菌产生的β－内酰胺酶比青霉素稳定，过敏反应发生率低，使用安全，故在临床上很受欢迎。头孢菌素按其发展顺序，并结合某些特点如抗菌谱、抗菌活性、对β－内酰胺酶的稳定性等不同，分为一、二、三、四代。第一代头孢菌素主要有头孢氨苄（…     

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.