抗生素含量测定方法的分析概述

抗生素作为一种抗菌物质,在现代医疗中起着非常重要的作用。2015版中华人民共和国药典共收录抗生素药品363种,所介绍的抗生素含量测定方法有4种。根据抗生素测定方法的统计,在这363种抗生素中,有275种采用高效液相色谱法;有75种采用抗生素微生物检定法;有8 种采用紫外-可见分光光度法;只有5种采用了滴定法。以最新的2015版中华人民共和国药典为基础,对抗生素的测定方法进行了分析概述,期望能在环境抗生素残留量的测定方面提供可借鉴的内容。     

抗生素在儿童患者中的使用状况

目的:了解我院(南华大学第一附属医院)儿童患者抗生素的使用情况;为相关治疗提供临床参考、方法:随机抽查我院儿科病历252份,填写“抗生素使用情况调查表”,用Excel软件统计分析数据。结果:抗生素使用率高达97％,抗生素联合使用率为15％。使用频率最高的是头孢菌素类达64．68％,其次是青霉素类达17．06％、大环内酯类达10．71％。结论:抗生素在我院儿童住院病人中被广泛使用;但主要是几种经验药,抗生素的科学使用性偏低。     

Experimental bases of directed transport of antibiotics in suppurative-inflammatory diseases of the liver and biliary tract

The possibility of use and effectiveness of directed transport of antibiotics in erythrocyte carriers in the treatment of suppurative-inflammatory diseases of biliary ducts has been studied on dogs. It has been found that erythrocyte carriers were resistant to desorption of antibiotics in the blood circulation. Pharmacokinetic investigation has shown the more prolonged collection of antibiotics in hepatic tissue in comparison with traditional intravenous route. The results of clinical, pharmacokinetic and morphological investigation have shown more effectiveness of directed transport of antibiotics to the liver in autologous erythrocyte carriers in treatment of suppurative diseases of biliary ducts in comparison with traditional methods of infusion of antibiotics. For reasons given it is recommended to use this method in clinical practice.     

Research progress on distribution,migration, transformation of antibiotics and antibiotic resistance genes (ARGs) in aquatic environment

Antimicrobial and antibiotics resistance caused by misuse or overuse of antibiotics exposure is a growing and significant threat to global public health. The spread and horizontal transfer of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) by the selective pressure of antibiotics in an aquatic environment is a major public health issue. To develop a better understanding of potential ecological risks die to antibiotics and ARGs, this study mainly summarizes research progress about: (i) the occurrence, concentration, fate, and potential ecological effects of antibiotics and ARGs in various aquatic environments, (ii) the threat, spread, and horizontal gene transfer (HGT) of ARGs, and (iii) the relationship between antibiotics, ARGs, and ARB. Finally, this review also proposes future research direction on antibiotics and ARGs.     

Incidence and possibilities of screening antifungal non-polyene antibiotics in actinomycetes

The author studied 114 strains of actinomycetes recovered from different geographical localities with different vegetation. Under submerse cultivation conditions 57% of the strains displayed antibiotic activity—48% antibacterial, 56% antifungal. As distinct from intracellular antibiotics, production of extracellular antibiotics was manifestly influenced by the composition of the fermentation medium. The commonest antifungal antibiotics were polyenes and non-polyenes, in the ratio 2∶1 Twenty strains produced non-polyene antifungal antibiotics, 14 of which corresponded to substances described in the literature. Only three strains produced antifungal non-polyenes singly; the others simultaneously formed basic antibacterial antibiotics of the type of streptomycin, streptothricin and neomycin or (also) polyene antibiotics, as a third component. Non-polyenes and polyenes did not occur together in the mycelium only or in fermentation fluid filtrate only. No correlation was found between the formation of non-polyenes and the place of origin of the strain. The possibility of screening new antibiotics is discussed.     

The sensitivity to antibiotics and chloramine B of opportunistic microorganisms isolated from patients

Strains of staphylococci, klebsiella, proteins, blue pus bacillus and enterobacteria resistant not only to antibiotics but also to chloramine, a disinfectant, were isolated from the test material samples obtained from patients with different purulent-inflammatory processes. The following strains are revealed among the test microorganisms: sensitive simultaneously to antibiotics and chloramine; sensitive to antibiotics but resistant to chloramine; sensitive to chloramine but resistant to antibiotics; simultaneously resistant both to antibiotics and chloramine.     

对安贞医院革兰阴性杆菌的耐药趋势调查

目的分析安贞医院感染菌中,居前5位的革兰阴性杆菌的耐药趋势,为临床合理使用抗生素提供必要依据。方法对2000～2002年该院分离的医院感染菌株中,居前5位的革兰阴性杆菌的耐药性,进行回顾性分析。结果革兰阴性杆菌中前5位细菌,对3代头孢菌素的耐药性增高。大多数细菌对亚胺培南和美洛培南敏感。阿米卡星的耐药性有所下降。大肠埃希菌对喹诺酮类抗生素耐药率在85％以上。结论不规范使用抗生素,使细菌的耐药性越来越高,交替使用抗生素可能是降低细菌对抗生素耐药性的有效方法。医院应宏观控制使用抗生素。     

炭样小单孢菌中抗生素生物合成相关蛋白的筛选

目的：筛选一株具有广谱抗菌活性的炭样小单孢菌JXNU-1中核苷类抗生素生物合成相关蛋白。方法：通过iTRAQ定量蛋白质组学技术对JXNU-1菌体生长期（36h）和产物合成期（108h）的差异蛋白进行鉴定和功能分析。结果：基于iTRAQ定量蛋白质组学技术共鉴定出炭样小单孢菌总蛋白质2390个,差异表达蛋白172个,在产物合成期（108h）表达上调76个、表达下调96个。通过蛋白GO和COG注释等功能分析,筛选出12个与抗生素合成密切相关蛋白和5个生物合成基因簇。结论：利用iTRAQ技术筛选出炭样小单孢菌JXNU-1的抗生素合成相关蛋白,为阐明该抗生素的生物合成机制奠定实验依据。     

Neutralization of endotoxin toxicity in chick embryos by antibiotics

Rifkind, David (University of Colorado Medical Center, Denver), and John D. Palmer. Neutralization of endotoxin toxicity in chick embryos by antibiotics. J. Bacteriol. 92:815-819. 1966.-Three cationic cyclic polypeptide antibiotics, polymyxin B sulfate colistin sulfate, and tyrocidine hydrochloride, were shown to neutralize endotoxin lethality in chick embryos. The neutralizing potency of these antibiotics was approximately equivalent, 0.06 to 0.11 mumole of antibiotic per mug of endotoxin. Methane sulfonation of colistin resulted in a 13-fold decrease in endotoxin-neutralizing potency. Other cationic cyclic polypeptide antibiotics were inactive, as well all other classes of antibiotics tested, including the neutral cyclic polypeptides. Several nonantibiotic polycationic proteins and polymers tested were also inactive. It is suggested that certain cationic cyclic polypeptide antibiotics neutralize by combining directly with the toxic moiety of the endotoxin molecule. Possibly this combination involves the cationic groups of the antibiotics and the polyphosphate groups of the phospholipid component of endotoxin.     

Effect of Macrolide Antibiotics on Macrophage Functions

Macrolide antibiotics have a variety of actions other than antimicrobial activities. Recently, it has been suggested that macrolide antibiotics act as immunomodulators. In this study, we evaluated the effects of macrolide antibiotics on macrophage functions. For the macrophage, we used the mouse macrophage cell line J774.1. The following effects of macrolide antibiotics on macrophage functions were evaluated: the effect of macrolide antibiotics on macrophage growth; the phagocytosis of beads; cytocidal activity against Candida albicans; and chemotaxis to lipopolysaccharide (LPS). Macrolide antibiotics except for azithromycin significantly stimulated the growth of the macrophage. In addition, pretreatment with macrolide antibiotics except for roxithromycin significantly stimulated the macrophage phagocytosis of beads, macrophage chemotaxis to LPS, and macrophage cytocidal activity against Candida albicans. These results suggest that macrolide antibiotics stimulate macrophage functions.     

Effect of sulfadiazine and trimethoprim on activated sludge performance and microbial community dynamics in laboratory-scale membrane bioreactors and sequencing batch reactors at 8°C

The effect of antibiotics sulfadiazine and trimethoprim on activated sludge operated at 8°C was investigated. Performance and microbial communities of sequencing batch reactors (SBRs) and Membrane Bioreactors (MBRs) were compared before and after the exposure of antibiotics to the synthetic wastewater. The results revealed irreversible negative effect of these antibiotics in environmentally relevant concentrations on nitrifying microbial community of SBR activated sludge. In opposite, MBR sludge demonstrated fast adaptation and more stable performance during the antibiotics exposure. Dynamics of microbial community was greatly affected by presence of antibiotics. Bacteria from classes Betaproteobacteria and Bacteroidetes demonstrated the potential to develop antibiotic resistance in both wastewater treatment systems while Actinobacteria disappeared from all of the reactors after 60 days of antibiotics exposure. Altogether, results showed that operational parameters such as sludge retention time (SRT) and reactor configuration had great effect on microbial community composition of activated sludge and its vulnerability to antibiotics. Operation at long SRT allowed archaea, including ammonium oxidizing species (AOA) such as Nitrososphaera viennensis to grow in MBRs. AOA could have an important role in stable nitrification performance of MBR-activated sludge as a result of tolerance of archaea to antibiotics. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 35: e2708, 2019     

Screening of antineoplastic antibiotics using a rapid method of evaluating their cytostatic effect on tumor cells

The study was aimed at development of a rapid method for estimating in vitro cytostatic action of antitumor antibiotics on the basis of intensity of inclusion of labeled precursors into nucleic acids of tumor cells which should be useful in primary screening of antibiotics with potential antitumor activity. The method was applied to substances isolated from 600 cultures of actinomycetes. 35 antibiotics showed antitumor activity; 8 of them were studied in detail. They proved to be novel antibiotics having antitumor activity in animals.     

Biochemical activity of opportunistic antibiotic and chloramine-sensitive and resistant microorganisms isolated from healthy and sick people

Activity of oxidation-reduction enzymes such as succinate dehydrogenase, peroxidase and catalase was studied in staphylococci isolated from healthy persons and patients as well as from the air and implements of medical institutions. The isolates were resistant either to antibiotics or to chloramine B or to the both. The results showed that development of resistance to antibiotics and chloramine B in the staphylococci was accompanied by a decrease in the activity of succinate dehydrogenase, peroxidase and catalase. In the strains resistant only to chloramine B the activity of the enzymes was practically at the same level as in the strains resistant only to antibiotics. In the strains resistant to both antibiotics and chloramine B, the activity of succinate dehydrogenase, peroxidase and catalase did not practically differ from that in the strains resistant either to antibiotics or to chloramine B.     

环境抗生素污染的微生物修复进展

近年来随着抗生素在畜牧业、水产养殖业以及医疗行业的广泛应用,大量抗生素通过排泄物进入环境,导致我国大面积水体及土壤环境中抗生素残留量急剧增高。环境中不同种类的抗生素的残留导致微生物种群结构失衡,对生态环境及人类造成极大危害。因此,解决抗生素残留问题是21世纪新型环境污染物领域的一个重要课题。已有研究显示,一些微生物能够以抗生素为碳源生存,可用于降解环境中残留抗生素,但人们对微生物降解抗生素的降解机制了解较少。文中概括了近十年来抗生素降解菌株和菌群对抗生素的去除情况,以及应用微生物菌群处理抗生素残留的技术方法,同时对未来利用微生物修复法减少环境中抗生素残留进行了展望。     

Pharmacophore-based strategy for the development of general and specific scFv biosensors for abused antibiotics

We developed fluorescent biosensor systems that are either general or selective to fluoroquinolone antibiotics by using a single-chain variable-fragment (scFv) as a recognition element. The selectivity of these biosensors to fluoroquinolone antibiotics was rationally tuned through the structural modification on the pharmacophore of fluoroquinolone antibiotics and the subsequent selection of scFv receptor modules against these antibiotics-based antigens using phage display. The resulting A2 and F9 scFv's bound to their representative antigen with a moderate affinity (K(D) in micromolar range as determined by surface plasmon resonance). A2 is a specific binder for enrofloxacin and did not cross-react with other fluoroquinolone antibiotics including structurally similar ciprofloxacin, while F9 is a general fluoroquinolone binder that likely bound to the antigen at the common pyridone-carboxylic acid pharmacophore. These scFv-based receptors were successfully applied to the development of one-step fluorescent biosensor which can detect fluoroquinolone antibiotics at concentrations below the level suggested in animal drug application guidelines. The strategy described in this report can be applied to developing convenient field biosensors that can qualitatively detect overused/misused antibiotics in the livestock drinking water.     

Detection of broad-spectrum aminoglycoside antibiotics through fluorescence-labeling aminoglycoside acetyltransferase(6')-Ii

Aminoglycosides are among the most commonly used antibiotics. The intensive use of aminoglycoside antibiotics has led to the problem of food contamination and the development of antibiotic-resistant bacteria. In the present study, we developed an effective method for easy sensitive detection of broad-spectrum aminoglycoside antibiotics. Aminoglycoside 6′-N-acetyltransferase family catalyzes the transfer of an acetyl group from acetyl coenzyme A (acetyl-CoA) to the 6′ amino group of the aminoglycoside, which is one of the most widespread determinants of aminoglycoside resistance. Because acetyl-CoA is naturally present only in living organisms, it is expected that the enzyme can bind with aminoglycoside antibiotics without catalysis in vitro. The enzyme was mutated for the introduction of a cysteine residue to flexible loops close to the binding site, which was then labeled with thio-labeling reagent fluorescein-5-maleimide. The labeled enzymes were characterized with kinetic and binding studies of various known aminoglycoside antibiotics. The binding of the labeled enzyme with aminoglycoside antibiotics causes a conformational change of the enzyme, which subsequently changes the hydrophobicity and hydrophilicity environment of fluorescent labeling reagent resulting in emission of fluorescence. This study provides a sensitive detection method for residual aminoglycoside antibiotics and strategies to screen and discover new effective aminoglycoside antibiotics.     

Sensitivity to antibiotics and the disinfectant chloramine of Staphylococci isolated from healthy and sick persons

Five hundred and twenty seven strains of Staphylococcus aureus with massive contamination of at least 10(3) when estimated quantitatively were tested for their sensitivity to antibiotics and chloramine B. The staphylococcal strains were isolated from patients, air and stock of rooms in medical institutions, from medical personnel and healthy persons having no long-term contacts with hospital media i. e. from pregnant women and workers of confectionery plants. Among the isolates there were strains simultaneously sensitive to antibiotics and chloramine B (16.6 per cent), sensitive to antibiotics but resistant to chloramine B (5.5 per cent), resistant to antibiotics but sensitive to chloramine B (63.1 per cent) and resistant to antibiotics and chloramine B (15.3 per cent). Staphylococci resistant simultaneously to antibiotics and chloramine B were isolated from the persons of all the groups and from the air and stock of the rooms in the medical institutions. This showed the necessity of controlling sensitivity or staphylococci circulating in hospital media not only to antibiotics but also to disinfectants for providing more efficient prophylaxis of intrahospital infections.     

乳酸杆菌制剂对应用抗生素大鼠体内TLR2 mRNA转录水平及相关因素影响的研究

目的动态观察乳酸杆菌制剂对应用抗生素大鼠肠道菌群结构和TLR2 mRNA转录水平的影响。方法采用细菌培养法定量检测肠道双歧杆菌、乳酸杆菌、肠杆菌和肠球菌;利用反转录聚合酶链反应技术测定大鼠肠黏膜组织、肠系膜淋巴结、肝脏和脾脏细胞TLR2 mRNA转录水平。结果应用抗生素可致肠道菌群失调和TLR2 mRNA转录水平的早期受抑制。乳酸杆菌制剂干预可迅速提高肠道乳酸杆菌数量,及早扶正肠道菌群结构,减轻由于应用抗生素引起的Toll样受体mRNA转录受抑程度。结论乳酸杆菌制剂早期干预可及早扶正肠道菌群结构,减轻TLR2 mRNA转录水平受抑制程度,为临床合理应用抗生素,早期益生菌干预提供理论依据。     

儿科病房抗生素相关性腹泻的临床观察

目的观察儿科病房抗生素相关性腹泻(antibiotic associated diarrhea,AAD)的临床表现。方法对983例使用抗生素的患儿进行分析,根据是否发生AAD分为两组,AAD组共有76例患儿,未发生AAD的对照组有907例患儿。分析AAD组患儿使用抗生素的情况,并对两组患儿的基本情况进行比较分析。结果对AAD患儿抗生素使用种类进行分析,发现导致AAD的抗生素主要有三类,其中美洛西林/舒巴坦使用率最高,为18.4%,其次为美洛西林、头孢哌酮/舒巴坦和阿奇霉素,均为14.5%。并且,AAD的发生与性别无关(P0.05)。但是AAD在体重较轻、低龄、抗生素使用时间较长和抗生素联用患儿中多发(P0.05)。这些因素均会导致患儿住院时间延长并出现重要器官损伤现象。结论儿科病房中抗生素的使用要合理科学,尽量减少AAD的发生。     

抗生素产生菌诱变育种的研究进展

一种抗生素能否产业化决定于抗生素产生菌菌种的产素水平。因而如何提高抗生素产生菌的产素水平成为抗生素研究工作者长期不懈探索的重要课题。其中,诱变育种以其技术设备简单、省时省力等优点得到了微生物育种工作者的青睐,在诱变育种技术上取得了巨大进展,为抗生素工业化生产发挥了重要作用。综述了抗生素产生菌的诱变育种研究进展。