启动IJMBioS

S. Gupte
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On this special auspicious occasion I would like to take opportunity to share some of my thoughts.\nThe medical microbiology revolves around three main areas and topics such as type's infectious diseases, diagnosis methods andtreatment options.  Over the past decades, major advances in the field of molecular biology, coupled with advances in multiplex real time PCR technologies have facilitated the development of high performing,innovative, low cost and syndrome based tests for the diagnosis of various bacteria, viruses and parasites  with the aid of   fast track diagnostics.  These technologies are particularly specialised in symptoms based disease approach as different pathogens can cause similar clinical pictures while diagnosed for  respiratory infections, gastroenteritis, sexually transmitted infections, fever, rash, childhood infections, hepatitis, meningitis, infections of the immune suppressed, tropical fever and many other infections. Fungal infections are increasing worldwide specially with increase in immune compromised patients. Correct and accurate laboratory diagnosis of fungal infections has become an essential part of the laboratory services.\n \nAfter achieving success in diagnosis,it's now a turn of a clinician to give most appropriate antimicrobial treatment from the available armament of antimicrobial agents.  At this point the gloomy scenario surfaces. Due to ever increasing number of resistant organisms treatment options for clinicians are very limited. Emergence of MRSA, VRSA, ESBL and MBL including NDM1 and so on have made one time considered most powerful antibiotics blunt in action. The number of strains resistant to different antibiotics and their ever increasing number revealed in several publications worldwide are really scary. The situation is really bad in Asian countries. Lot of discussion goes and finally blame points at uncontrolled misuse of antibiotics. Though it is true, there are certain associated socio-economic issues that need to be considered. The  clinician is often forced to  go for empirical  antibiotic treatment due to high cost of susceptibility tests needed to be performed before starting the appropriate antibiotic treatment and moreover even if he wants,  it not easily  available particularly in rural areas. \nAdditionally, leading international Pharma companies have either stopped their search for new antibiotics or slowed down   and instead prefer to invest in lifestyle  diseases  such as high blood pressure, diabetes and asthma due to their higher shelf life, unlike that of  antibiotics. The    safety issues and very high cost of clinical trials coupled with uncertainty of final success have made   development of NCEs less rewarding.  \nThe art of antibiotic discovery from natural sources such as soil is slowly dying out even though it still has a very high potential to reward. Now days it is possible to give outstanding resultstogether with the help of   sophisticated and advanced analytical identification tools and database of known antibiotics, not available during the early days of antibiotic research.\nToday the countries of the world are fast connected with each other. Any asymptomatic  carrier can carry deadly resistant pathogens fromone end of the world to another within less than 24 hours without even his or her knowledge and without any suspect of the regulatory authority. It is very difficult now to stop this spread even in so called isolated advanced countries.\nAnother reason for immergence of antimicrobial resistance is also need to be equally understood. The suboptimal doses when given during the therapy can create antibiotic levels lower than the Mutant Prevention Concentration (MPC) and thereby give chance to slowly growing resistant subpopulation to grow which then increase in number during the same treatment. It is essential that clinician has knowledge of PK-PD effect of antibiotics and by what parameter the antibiotic acts. These are governed by either Cmax /MIC or AUC/MIC or time above MIC. For example Fluoroquinoles act by Cmax/MIC and therefore a single dose once a day is often recommended whereas beta lactams class of antibiotics need longer time above MIC level to act and hence frequent dosing is practised. Any compromise with these parameters could lead to development of resistant strains.\nThe five hours short duration incubation in automated susceptibility test is based on development and measurement of optical density. However, resistant mutants which are few in number compared to a large sensitive population fail to impart turbidity and hence the culture is labelled as sensitive. This is a major error in susceptibility testing. 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引用次数: 0

摘要

我非常高兴能在尼泊尔研究中心的努力下,成为《国际医学与生物医学科学杂志》第一期创刊号的一名小撰稿人。顾名思义,本刊主要致力于生物医学和医学科学及其相关主题。在这个特别吉祥的时刻,我想借此机会分享我的一些想法。医学微生物学围绕着传染病类型、诊断方法和治疗方案三个主要领域和主题展开。过去几十年来,分子生物学领域的重大进展,加上多重实时聚合酶链反应技术的进步,促进了在快速诊断的帮助下,开发出高性能、创新、低成本和基于综合征的检测方法,用于诊断各种细菌、病毒和寄生虫。这些技术特别专门用于以症状为基础的疾病方法,因为不同的病原体在诊断呼吸道感染、肠胃炎、性传播感染、发烧、皮疹、儿童感染、肝炎、脑膜炎、免疫抑制感染、热带病和许多其他感染时,可能会引起类似的临床症状。真菌感染在世界范围内正在增加,特别是随着免疫功能受损患者的增加。正确、准确的真菌感染实验室诊断已成为实验室服务的重要组成部分。在获得诊断成功后,现在轮到临床医生从现有的抗菌药物中给予最适当的抗菌治疗。在这一点上,令人沮丧的情景浮出水面。由于耐药菌数量不断增加,临床医生的治疗选择非常有限。MRSA、VRSA、ESBL和MBL包括NDM1等的出现,使得一度被认为最强大的抗生素失去了作用。对不同抗生素具有耐药性的菌株的数量及其不断增加的数量在世界各地的几份出版物中被披露,这真的很可怕。亚洲国家的情况非常糟糕。大量的讨论,最后归咎于不受控制的滥用抗生素。虽然这是事实,但也有一些相关的社会经济问题需要考虑。临床医生往往被迫采用经验性抗生素治疗,因为在开始适当的抗生素治疗之前需要进行敏感性测试,费用很高,而且即使他想这样做,也不容易获得,特别是在农村地区。此外,领先的国际制药公司要么停止了对新抗生素的研究,要么放慢了研发速度,转而更愿意投资于高血压、糖尿病和哮喘等生活方式疾病,因为它们的保质期比抗生素更长。安全性问题、临床试验的高成本以及最终成功的不确定性使得nce的发展不那么有回报。从土壤等自然资源中发现抗生素的技术正在慢慢消亡,尽管它仍然有很高的回报潜力。现在,在复杂和先进的分析鉴定工具和已知抗生素数据库的帮助下,有可能给出出色的结果,这在抗生素研究的早期是不可用的。今天,世界各国之间的联系非常紧密。任何无症状携带者都可以在不到24小时内将致命的耐药病原体从世界的一端带到另一端,而他或她甚至不知情,也没有任何监管当局的怀疑。即使在所谓的孤立的发达国家,现在也很难阻止这种传播。抗菌素耐药性出现的另一个原因也需要同样了解。在治疗期间给予的次优剂量可产生低于突变预防浓度(MPC)的抗生素水平,从而使缓慢生长的耐药亚群有机会生长,然后在相同治疗期间数量增加。临床医生了解抗生素的PK-PD效应以及抗生素通过什么参数起作用是至关重要的。这些由Cmax /MIC或AUC/MIC或高于MIC的时间控制。例如,氟喹诺类抗生素通过Cmax/MIC起作用,因此通常建议每天服用一次,而β -内酰胺类抗生素需要更长时间才能达到MIC水平,因此需要频繁给药。对这些参数的任何妥协都可能导致耐药菌株的产生。自动药敏试验中的5小时短时间孵育是基于光密度的开发和测量。然而,与大量敏感群体相比,抗性突变体的数量很少,因此不能赋予浊度,因此培养物被标记为敏感。 这是敏感性测试中的一个主要错误。为了克服这一问题,E-test MIC方法是更好的选择,因为在孵育24小时后,抗性突变体在抑制区以分离菌落的形式生长,可以清楚地显示它们的存在。这将有助于临床医生在适当的时候做出明智的决定,选择更有效和合适的抗生素治疗方案。这是导致患者体内产生耐药菌库及其随后传播的原因之一,而且还可能导致死亡。国家一级的抗生素耐药性监测规划如果定期开展,将有助于正确地了解预警情况的严重性,也有助于判断所实施的抗生素耐药性控制规划的有效性。制药公司的共同责任是避免在不了解个别合作伙伴的PK -PD的情况下引入不合理的抗生素组合。在抗微生物治疗中,在治疗过程中,感染部位单个成分的浓度在一起是至关重要的,正如在体外评估实验中观察到的那样。同样,体外联合研究的MIC结果必须显示耐药菌株的MIC落在CLSI指南推荐的敏感范围内。研究人员必须记住,高质量研究的结果应该带来新的发现,更好地理解或洞察早期的发现,或者理想地提出更好的治疗方案。发表对已知数据的再确认有时是必要的。然而,当这些类型的出版物非常频繁地出现在期刊上时,并不会导致科学的进步。最后,我祝贺IJMBioS团队在这项崇高的事业中取得了圆满成功。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Initiation of IJMBioS
It gives me a great pleasure to be a small contributor to the first inaugural issue of “International Journal of Medicine & Biomedical Sciences” being published from Nepal with efforts put in by Nepalese Researches. As the name suggests, this journal is mainly devoted to Biomedical Sciences & Medical sciences and related topics. On this special auspicious occasion I would like to take opportunity to share some of my thoughts. The medical microbiology revolves around three main areas and topics such as type's infectious diseases, diagnosis methods andtreatment options.  Over the past decades, major advances in the field of molecular biology, coupled with advances in multiplex real time PCR technologies have facilitated the development of high performing,innovative, low cost and syndrome based tests for the diagnosis of various bacteria, viruses and parasites  with the aid of   fast track diagnostics.  These technologies are particularly specialised in symptoms based disease approach as different pathogens can cause similar clinical pictures while diagnosed for  respiratory infections, gastroenteritis, sexually transmitted infections, fever, rash, childhood infections, hepatitis, meningitis, infections of the immune suppressed, tropical fever and many other infections. Fungal infections are increasing worldwide specially with increase in immune compromised patients. Correct and accurate laboratory diagnosis of fungal infections has become an essential part of the laboratory services.   After achieving success in diagnosis,it's now a turn of a clinician to give most appropriate antimicrobial treatment from the available armament of antimicrobial agents.  At this point the gloomy scenario surfaces. Due to ever increasing number of resistant organisms treatment options for clinicians are very limited. Emergence of MRSA, VRSA, ESBL and MBL including NDM1 and so on have made one time considered most powerful antibiotics blunt in action. The number of strains resistant to different antibiotics and their ever increasing number revealed in several publications worldwide are really scary. The situation is really bad in Asian countries. Lot of discussion goes and finally blame points at uncontrolled misuse of antibiotics. Though it is true, there are certain associated socio-economic issues that need to be considered. The  clinician is often forced to  go for empirical  antibiotic treatment due to high cost of susceptibility tests needed to be performed before starting the appropriate antibiotic treatment and moreover even if he wants,  it not easily  available particularly in rural areas.  Additionally, leading international Pharma companies have either stopped their search for new antibiotics or slowed down   and instead prefer to invest in lifestyle  diseases  such as high blood pressure, diabetes and asthma due to their higher shelf life, unlike that of  antibiotics. The    safety issues and very high cost of clinical trials coupled with uncertainty of final success have made   development of NCEs less rewarding.   The art of antibiotic discovery from natural sources such as soil is slowly dying out even though it still has a very high potential to reward. Now days it is possible to give outstanding resultstogether with the help of   sophisticated and advanced analytical identification tools and database of known antibiotics, not available during the early days of antibiotic research. Today the countries of the world are fast connected with each other. Any asymptomatic  carrier can carry deadly resistant pathogens fromone end of the world to another within less than 24 hours without even his or her knowledge and without any suspect of the regulatory authority. It is very difficult now to stop this spread even in so called isolated advanced countries. Another reason for immergence of antimicrobial resistance is also need to be equally understood. The suboptimal doses when given during the therapy can create antibiotic levels lower than the Mutant Prevention Concentration (MPC) and thereby give chance to slowly growing resistant subpopulation to grow which then increase in number during the same treatment. It is essential that clinician has knowledge of PK-PD effect of antibiotics and by what parameter the antibiotic acts. These are governed by either Cmax /MIC or AUC/MIC or time above MIC. For example Fluoroquinoles act by Cmax/MIC and therefore a single dose once a day is often recommended whereas beta lactams class of antibiotics need longer time above MIC level to act and hence frequent dosing is practised. Any compromise with these parameters could lead to development of resistant strains. The five hours short duration incubation in automated susceptibility test is based on development and measurement of optical density. However, resistant mutants which are few in number compared to a large sensitive population fail to impart turbidity and hence the culture is labelled as sensitive. This is a major error in susceptibility testing. To overcome this problem, E-test MIC method is better option since on 24 hr incubation, the resistant mutants that grow in the form of isolated colonies in the zone of inhibition   can clearly show their presence.  This observation would help clinician to take informed decision at right time to choose a more efficacious and appropriate antibiotic treatment protocol. This is one of the reasons which results in not only creating reservoir of resistant organisms in patient’s body and its subsequent spread but could also result in mortality. The national level antibiotic resistance surveillance program if undertaken on regular   intervals of time would help   draw correct picture of gravity of alarming situation and also to judge the effectiveness of program implemented to control AMR. It is a joint responsibility of Pharma companies to refrain themselves from introducing irrational antibiotic combinations without understanding the PK –PD of an individual partner. In antimicrobial therapy, the concentration of an individual component at the site of infection when present together during the therapy is critical as observed in in-vitro evaluation experiments. Similarly, MIC results in in-vitro combination study   must show MICs of resistant strains falling in the sensitive range as recommended by CLSI guideline. Researchers have to keep in mind that the outcome of quality research should lead to new findings, better understanding or insight into earlier findings or   ideally suggesting a better treatment option. The publication of reconfirmation of known data is sometimes essential. However, these type of publication when very frequently appear in journals do not lead to advancement of science. Finally I congratulate IJMBioS team a good success in this noble endeavour.
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