New therapeutic approaches by using microorganism-derived compounds

The role of natural products as a source for remedies has been recognized since ancient times. Despite major scientific and technological progress in combinatorial chemistry, drugs derived from natural product still make an enormous contribution to drug discovery today. Nature is an attractive source of new therapeutic candidate compounds since a tremendous chemical diversity is found in millions of species of plants, animals, marine organisms and microorganisms. Microorganisms such as bacteria and fungi have been invaluable to discover drugs and lead compounds. These microorganisms produce a large variety of antimicrobial agents which have evolved to give their hosts an advantage over their competitors in the microbiological world. The screening of microorganisms became highly popular after the discovery of penicillin but in recent years the list of antibacterial agents (bacteria- or fungi-derived) has increased considerably with the arrival of cephalosporins, tetracyclines, aminoglycosides, rifamycins, and chloramphenicol. Although most of the drugs derived from microorganisms are used in antibacterial therapy, some microbial metabolites have provided lead compounds in other fields of medicine. For example: the fungal metabolite lovastatin, which was the lead compound for a series of drugs that lower cholesterol levels, the ciclosporin (fungal metabolite) currently used to suppress the immune response after transplantation operations and sirolimus- a bacterium-derived macrolide- used in the treatment of some cancers. The aim of this review is to analyze the current uses and the future applications in therapeutic treatments of microorganism-derived products (MdPs) and discuss the results obtained in the some clinical trials.     

多利培南的药理学特点与临床应用评价

目的:概括多利培南的药理学特点,评价其临床应用。方法:收集国内外相关文献,从多利培南的作用机制、抗菌活性、耐药机制、药代动力学等方面进行分析、评价。结果与结论:多利培南是新型碳青霉烯类抗生素,具有较广的抗菌谱,对革兰阳性菌、革兰阴性菌和厌氧菌均有较强的抗菌作用。     

植物内生菌抑菌机制和抑菌次生代谢产物的研究进展

植物内生菌是一种不可多得的微生物资源,具有广泛的应用价值,特别是药用植物内生菌近年来受到越来越多学者的青睐。内生菌的代谢产物是新型化合物和药理学的潜在来源,能够帮助人类解决抗生素的耐药性、植物遭遇病虫害侵袭以及动物的健康等问题,因此对具有抗菌作用的内生菌进行总结具有重要意义。从抑菌机制、抑菌活性次生代谢产物方面进行综述,并对植物内生菌的开发利用进行展望。     

Acetylenic anticancer agents

This review is a comprehensive survey of acetylenic anticancer agents obtained from living organisms. Acetylenic metabolites belong to a class of molecules containing triple bond(s). They are found in plants, fungi, microorganisms, and marine invertebrates. Although acetylenes are common as components of terrestrial plants, fungi, and bacteria, it is only within the last 30 years that biologically active polyacetylenes having unusual structural features have been reported from plants, cyanobacteria, algae, invertebrates, and other sources. Naturally occurring aquatic acetylenes are of particular interest since many of them display important biological activities and possess antitumor, antibacterial, antimicrobial, antifungal, phototoxic, HIV inhibitory, and immunosuppressive properties. There is no doubt that they are of great interest, especially for the medicinal chemistry, and/or pharmaceutical industries. This review presents structures and describes cytotoxic activities of more than 300 acetylenic metabolites isolated from living organisms.     

Antimicrobial Activity of Terminalia catappa, Manilkara zapota and Piper betel Leaf Extract

Aqueous and methanol extract of the leaves of Terminalia catappa L., Manilkara zapota L. and Piper betel L. were evaluated for antibacterial activity against 10 Gram positive, 12 Gram negative bacteria and one fungal strain, Candida tropicalis. Piperacillin and gentamicin were used as standards for antibacterial assay, while fluconazole was used as standard for antifungal assay. The three plants showed different degree of activity against the microorganisms investigated. The methanolic extract was considerably more effective than aqueous extract in inhibiting the investigated microbial strains. The most active antimicrobial plant was Piper betel.     

第5代头孢菌素头孢洛林酯的药理研究进展与临床应用评价

目的:概括头孢洛林酯(ceftraoline fosamil)的药理学特点,评价其临床应用。方法:收集国内外相关文献,从头孢洛林酯的作用机制、抗菌活性、药代动力学等方面进行分析、评价。结果与结论:头孢洛林酯是头孢菌素类抗菌药物,具有较广的抗菌谱,对革兰阳性菌、革兰阴性菌和厌氧菌均有较强的抗菌作用。     

Phytochemical and biological activities of some Iranian medicinal plants

ContextDue to adverse effects of synthetic compounds, there is a growing interest in utilization of plant-derived natural products in the pharmaceutical and food industries. Iranian endemic medicinal plants widely used in traditional practice have attracted much attention as antibacterial and antioxidant agents.ObjectiveThis review attempts to compile the accessible scientific research pertained to phytochemical compounds, antibacterial and antioxidant effects of essential oils obtained from some of the most widely used and distributed medicinal plants in Iran.MethodsThis review has been compiled using references via reliable databases (Google Scholar, SID and Science Direct) from 2010 to 2020. This literature review was limited to references published in English and Persian languages.ResultsBased on studies heretofore carried out, essential oils isolated from mentioned medicinal plants exhibited strong antioxidant activity which is attributed to their main phytochemical compounds; thymol, carvacrol, p-cymene and γ-terpinene. In addition, the antibacterial activities of essential oils of most plant species from Apiaceae and Asteraceae families were more susceptible against Gram-positive bacteria; Staphylococcus aureus and Bacillus cereus than Gram-negative bacteria; however, essential oils of other studied plant species manifested similar behaviours against both Gram-positive and -negative bacteria.ConclusionsAs there is rich ethnobotanical knowledge behind Iranian endemic medicinal plants, further scientific research is required to prove their safety and efficacy. This review revealed that there are numerous valuable medicinal plants adoptable in food and pharmaceutical industries in the near future.     

抗菌药物消耗量与常见革兰阴性细菌耐药性分析

目的 统计分析某三甲医院2011年-2013年抗菌药物使用情况及革兰阴性细菌耐药率,为临床降低细菌耐药性和合理使用抗菌药提供参考依据。方法 采用回顾性调查方法对2011年-2013年送检病原菌培养结果、同期各类别抗菌药物累计使用频度和细菌耐药率情况进行统计分析。结果 2011年-2013年排名前五位的革兰阴性病原菌均为大肠埃希菌、鲍曼不动杆菌、铜绿假单胞菌、肺炎克雷伯菌及阴沟肠杆菌,每年所占比例无明显变化。抗菌药物总用药频度逐年减少,从2011年的255456.37 DDDs下降到2013年的155024.25 DDDs,头孢菌素 酶抑制剂类及大环内酯类用量排名逐年升高,三四代头孢菌素及喹诺酮类类用量排名则逐年减少,抗真菌类及碳青霉烯类排名无明显变化。各类细菌对阿莫西林耐药率均较高,2013年基本达到100%,鲍曼不动杆菌及铜绿假单胞菌对哌拉西林他唑巴坦耐药率逐年上升,鲍曼不动杆菌对β-内酰胺类类抗菌药呈逐渐耐药趋势。 结论 我院的抗菌药物使用频度呈逐年下降的趋势,而部分细菌的耐药率有增加的趋势,需要更加合理使用抗菌药物,以减缓目前的耐药形式。     

Antimicrobial activity of carvacrol: current progress and future prospectives

During the last few years the scientific community has shown a considerable interest in the study of plant materials as sources of new compounds to be processed into antimicrobial agents. In this context, carvacrol, a monoterpenic phenol, has emerged for its wide spectrum activity extended to food spoilage or pathogenic fungi, yeast and bacteria as well as human, animal and plant pathogenic microorganisms including drug-resistant and biofilm forming microorganisms. The antibacterial activity of carvacrol has been attributed to its considerable effects on the structural and functional properties of cytoplasmatic membrane. The data reported in this review provide an overview of the published literature regarding the antimicrobial properties of carvacrol and the recent patents claimed in order to highlight its future applications as a new antimicrobial agent. These could concern either the natural preservation in the cosmetic and food industries or an alternative which supports the conventional antimicrobial protocols. Interestingly, carvacrol alone or associated with one or more synergistic products could be incorporated in different formulations for biomedical and food packaging applications. However, more detailed safety investigations and in vivo studies should be carried out so that this molecule could be used in the future.     

Metal,metal oxide and polymeric nanoformulations for the inhibition of bacterial quorum sensing

Antibiotic resistance of bacteria has caused a significant public health challenge and economic problem, resulting in a necessity to find efficient antibacterial agents. Conventional bactericidal agents hinder the growth of bacteria by slowing down the cell wall synthesis or disturbing bacterial DNA replication, protein production or other bacterial cellular metabolism that can augment natural selection pressure for turning up new antibiotic-resistant strains. Virulence properties and biofilm formation of bacteria are orchestrated by quorum-sensing systems. These quorum-sensing systems normally control antimicrobial production; and targeting these systems using metal-based nanoparticles or polymeric nanoparticles can be considered as powerful antibacterial treatments owing to their specific physicochemical and therapeutic properties. In this review, recent advances and challenges related to the inactivation of quorum-sensing systems by these nanoparticles are presented to obtain comprehensive viewpoints for future studies.     

以细菌细胞壁为靶点的抗菌药物研究进展

随着细菌耐药率的升高和产NDM-1、KPC等超级细菌的不断检出,研发新型抗菌药物成为人类健康的迫切需要。细胞壁是人体及动物细胞没有而细菌与植物细胞所特有的结构,以细胞壁为靶点的抗菌药物具有高选择性、低毒性的优势,一直是抗菌药物靶点研究的热点。本文就细菌细胞壁合成过程、细胞壁抑制剂的筛选和作用于细菌细胞壁合成的抗菌药物研究进展做一简要综述。     

以细菌细胞壁为靶点的抗菌药物研究进展

With the increasing prevalence of bacterial resistance and the continuous detection of super bacteria, such as NDM-1 and KPC producers, the development of new antibacterial drugs has become an urgent need in health care. The cell wall is a unique structure of bacterial and plant cells that human and animal cells lack. The antibacterial drugs targeting the cell wall have the advantages of high selectivity and low toxicity. Thus, they have been a hot spot in the research of antibacterial drugs. This paper reviews the synthesis process of bacterial cell wall, the screening of cell wall inhibitors, and the advances of research on antimicrobial agents that act on cell wall     

海洋微生物活性物质的研究近况

海洋微生物(MM)包括海洋细菌、真菌和放线菌,对其研究发现许多独特的海洋生物活性物质,通过对这些海洋生物活性物质的提取、药理研究,为新药的开发和各种疑难疾病的治愈提供了新的希望。综述MM产生的生物活性物质,如抗肿瘤、抗菌、抗病毒以及生物保健、生物杀虫和降解石油等功能方面的研究近况,为我国利用MM资源的开发与利用提供参考。     

细菌耐药监测结果与抗生素合理使用

目的通过对本院抗菌药物临床应用频度及本地区分布、细菌耐药情况的分析,以促进临床抗菌药物的合理使用。方法采用限定日剂量（DDD）法分析本院各种抗菌药物的使用情况,回顾性调查本院2012年检出的细菌及其药物敏感试验结果。细菌培养及药敏检测采用外购药敏试纸,按照《全国临床检验操作规程》第3版要求进行常规鉴定。根据细菌耐药监测数据,分析病原菌对抗菌药物的耐药情况。结果细菌培养共收集有效标本1096份,分离鉴定出致病菌267株．阳性率24．4％,其中革兰阳性菌占30．2％．革兰阴性菌占69．8％,临床分离出病原菌主要有大肠埃希菌、葡萄球菌属、铜绿假单胞菌等,其中大肠埃希菌检出最多,多数致病菌对常用抗生素耐药率较高。结论对细菌进行耐药监测及分析,可为临床经验合理用药提供有力的技术支持,对临床合理选择抗菌药物具有重要价值。     

Synthesis and evaluation of analgesic/ anti-inflammatory and antimicrobial activities of 3-substituted- 1,2,4-triazole-5-thiones

In this study, the synthesis of a novel series of Mannich bases of 5-mercapto-3-aryl-1,2,4-triazoles is described. The structures attributed to compounds la-5e were elucidated using IR and 1H-NMR spectroscopic techniques besides elemental analysis. The formation of 1-aminomethyl-3-substituted-1,2,4-triazole-5-thiones - not the isomeric 3-substituted-4-aminomethyl-1,2,4-triazole-5-thiones was unambiguously confirmed by X-ray crystallographic analysis of 1c. The compounds were examined for their in vivo anti-inflammatory and analgesic activity in two different bioassays, namely carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing a nonsubstituted phenyl group at C-3 position of the triazole ring (1a-e). The compounds were also evaluated for their in vitro antimicrobial activity against a series of gram positive bacteria [Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212)], gram negative bacteria [Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)] and yeast-like microorganisms [Candida albicans (ATCC 90028), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019)]. One series of the examined compounds (3a-e) exhibited better antibacterial activity especially against gram positive bacteria than against gram negative bacteria. Compounds 2c, 3b, and 3e were found to be more effective against C. parapsilosis compared with the other derivatives (MIC: 16 microg/mL).     

呋喃妥因对革兰阴性杆菌的抗菌活性分析

目的 了解呋喃妥因对革兰阴性杆菌的抗菌活性,为临床合理使用呋喃妥因提供依据.方法 监测某医院2009年1月至2012年12月临床分离的革兰阴性杆菌5 589株;采用VITEK 2 Compact全自动细菌培养鉴定仪进行细菌鉴定和药敏试验,以Whonet 5.6软件进行数据分析.结果 大肠埃希菌和产酸克雷伯菌对呋喃妥因的抗菌活性较好（耐药率＜4.3%）,阴沟肠杆菌和肺炎克雷伯菌对呋喃妥因的抗菌活性尚好（耐药率25.6%～36.3%）,铜绿假单胞菌、鲍曼不动杆菌、奇异变形菌和黏质沙雷菌对呋喃妥因的抗菌活性较差（耐药率93.7%～98.9%）,耐亚胺培南铜绿假单胞菌（IRPA）、耐碳青霉烯类抗菌药物鲍曼不动杆菌（CR-AB）和耐碳青霉烯类抗菌药物肠杆菌科细菌（CRE）对呋喃妥因的耐药率分别为100.0%（108/108）、100.0% （335/335）和96.1% （74/77）.结论 呋喃妥因对尿液、血液、脓汁和分泌物标本中分离的大肠埃希菌的抗菌活性较好;痰液标本中分离的铜绿假单胞菌和鲍曼不动杆菌对呋喃妥因的耐药率较高.     

New developments in antimicrobial use in sepsis

Over the past decade, trends in antimicrobial resistance, epidemiology, and drug development have occurred that affect both the empiric and definite selection of antimicrobials in the septic patient. The rapid spread of highly pathogenic community-associated methicillin resistant Staph aureus (MRSA) requires clinicians to consider the inclusion of empiric coverage for MRSA even in community-acquired sepsis. Moreover, vancomycin appears to be losing its effectiveness, and while a number of new agents with broad gram positive activity have been licensed, none have emerged as clearly superior. An alarming increase in the number of hospital-acquired infections due to multi-drug resistant gram negative bacteria has also occurred, and few new gram negative drugs are in development. Clinicians, faced with Pseudomonas aeruginosa or Acinetobacter baumanii isolates resistant to all commonly used drugs, must resort to toxic older drugs such as colistin or therapy combining drugs not effective as monotherapy. Based on a desire to limit overall antimicrobial use, a re-evaluation of older data in both the neutropenic and non-neutropenic host has called into question the common practice of using combination therapy for some gram negative infections. An emerging consensus advocates emphasizing local unit specific antimicrobial sensitivity data in selecting empiric therapy and determining if combination therapy is required. New antifungal drugs and a better understanding of the risk factors for infection with Candida spp. has altered the approach to empiric and definitive treatment of Candida infections in the septic patient.     

Antibacterial Activity of Some Medicinal Plants of Papua New Guinea

Crude drug samples were prepared from stem bark of 16 medicinal plants belonging to 9 different families, and screened for antibacterial activities against Gram positive (Bacillus subtilis and Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Most of them showed good antibacterial activity against Gram positive bacteria, and some of them exhibited antibacterial activity against Gram positive as well as Gram negative bacteria.     

头孢吡肟对重症监护病房院内感染细菌的体外抗菌活性研究

目的 :观察头孢吡肟对重症监护病房(ICU)院内感染细菌的体外抗菌活性。方法 :以纸片扩散法检测头孢吡肟与其他 15种常用抗菌药对ICU院内细菌感染病人感染部位培养分离出的 174株革兰阴性 (G- )杆菌 ,74株革兰阳性 (G+)球菌体外抗菌活性。结果 :头孢吡肟对G- 杆菌的抗菌活性高于常用第 2代和第 3代头孢菌素 ,与环丙沙星和庆大霉素类似 ,低于亚胺培南 西司他丁、阿米卡星、头孢哌酮 舒巴坦等。头孢吡肟对G+球菌的抗菌活性高于第 2代和第 3代头孢菌素 ,与亚胺培南 西司他丁及阿米卡星和奈替米星类似 ,但对耐甲氧西林的金黄色葡萄球菌和表皮葡萄球菌的抗菌活性很低。结论 :在ICU院内感染流行病学监测指导下 ,头孢吡肟可作为经验性治疗院内细菌感染的首选抗生素之一。     

Salicylanilide ester prodrugs as potential antimicrobial agents--a review

Salicylanilides have been a subject of interest in medicinal chemistry as a group with a wide range of biological activities. The antibacterial (including antimycobacterial) and antifungal activities have come to be viewed as very significant. The synthesis of new prodrugs to counter a number of problematic properties of salicylanilides is a current trend. This article brings together the known basic facts about these prodrugs, particularly about the different mechanisms of the antimicrobial action of salicylanilides, including salicylanilide toxicity and undesired effects. The largest part of this group consists of antimicrobial salicylanilide esters with different organic acids, e.g. acetates, carbamates, esters with N-protected amino acids, and mutual antibacterial compounds with known antibacterial agents (β-lactames and linezolid), with the activity and structure-activity relationships of these compounds being of particular interest. This review summarizes the activity of salicylanilides as potential virulence inhibitors attributable to a blockade of the type III secretion pathway. Many salicylanilide ester derivatives have been demonstrated an effective and promising treatment against pathogenic fungi and bacteria (especially against Gram-positive, tuberculous and atypical mycobacterial strains), including strains such as methicillin-resistant Staphylococcus aureus and isoniazid-resistant mycobacteria which are resistant to one or more clinically used drugs.