6000张抗菌药物处方专项点评分析及监管措施的探讨

目的:对我院门诊不合理使用抗菌药物处方进行分析,提高我院合理使用抗菌药物水平,探讨不合理使用抗菌药的原因及合理使用抗菌药的监管措施。方法:利用本院抗菌药处方信息系统,抽取2016年1月~12月抗菌药物处方,每月抽查抗菌药处方500张,包括16个科室共6000张进行处方点评,将药物选择不适宜;药物选择起点高,用法用量不适宜;溶液的浓度不适宜;溶媒量不适宜;联合用药是不适宜,诊断不规范,无适应症用药,重复用药,疗程偏长汇总分析。结果:不合理处方涉及16个科室,1160张不合理抗菌药处方,占抽取处方的19.33%,不合理处方包括十方面的内容,共1340处,占总抽查处方的22.33%。结论:我院门诊抗菌药物使用存在不合理性,不合理抗菌药处方占总抽查处方的百分率偏高,抗菌药物专项点评有利于发现科室存在的普遍问题,提出干预措施为持续改进提供参考。     

ICU下呼吸道多重耐药菌医院感染的病原学临床特征及易感因素分析

摘要 目的：研究ICU下呼吸道多重耐药菌医院感染的病原学临床特征及易感因素。方法：选择2020年1月到2022年12月于我院ICU住院治疗的216例下呼吸道感染者,按照是否发生多重耐药菌感染分为研究组113例,对照组103例。分析两组患者感染相关因素的数量分布情况,通过Logistic回归分析多重耐药菌医院感染的危险因素。采用全自动细菌鉴定仪对菌种进行鉴定,采用K-B纸片法进行药敏试验,并分析多重耐药菌感染的病原学分布及对常用抗菌药物的耐药性。结果：（1）与对照组相比,研究组患者感染相关因素的分布率更高;（2）住院时间>3个月、使用糖皮质激素治疗、应用机械通气治疗、其他细菌感染、血红蛋白含量<100 g/L、抗菌药物使用时间>15 d、抗菌药物使用种类>4种、使用免疫抑制剂是ICU下呼吸道多重耐药菌感染的危险因素;（3）113例研究组共培养出细菌菌株93株,其中革兰氏阴性菌52株（55.91%）,革兰氏阳性菌25株（26.88%）,革兰氏阴性菌中较多的是铜绿假单胞菌（22株）、鲍曼不动杆菌（13株）、肺炎克雷伯菌（12株）;革兰氏阳性菌中最多的是肺炎链球菌（11株）和金黄色葡萄球菌（11株）;（4）耐药情况：铜绿假单胞菌对莫西沙星耐药率较低（15.83%）,肺炎克雷伯菌对亚胺培南耐药率较低（17.56%）,鲍曼不动杆菌对头孢哌酮/舒巴坦耐药率较低（16.37%）,金黄色葡萄球菌、肺炎链球菌对万古霉素无耐药性。结论：住院时间>3个月、使用糖皮质激素治疗、应用机械通气治疗、其他细菌感染、血红蛋白含量<100 g/L、抗菌药物使用时间>15 d、抗菌药物使用种类>4种、使用免疫抑制剂是多重耐药感染的独立危险因素。本院ICU下呼吸道感染以革兰氏阴性杆菌为主,应根据病原菌选择耐药性低的药物,并针对危险因素采取有效措施。     

Leukolysis reaction in the diagnosis of allergy to antibacterial preparations in pulmonology]

The experiment included 109 patients with non-specific pathological processes in the lungs. i.e. 21 cases with acute and 55 cases with chronic pneumonia and 33 cases with bronchial asthma with or without chronic pneumonia. Clinically intolerance of the antibacterial drugs was observed in 39 patients and increased leucolysis (above 15 per cent) was observed sometimes more frequently. Only with the use of penicillin the difference was 1.6 times. Out of 39 patients with clinical signs of allergy to antibiotics or sulphanilamide only 20 showed the signs of increased leucolysis on the use of the respective drug. No correlation between the percentage of the leucolysis cases due to antibiotics or sulphanilamides and the clinical signs of their intolerance was observed. The use of such drugs by a person or even only his presence in the hospital often induced increased leucolysis which may be considered as an indication of the person sensibilization to them.     

The decline of antibiotic era--new approaches for antibacterial drug discovery

Infectious diseases still remain the main cause of human premature deaths; especially in developing countries. The emergence and spread of pathogenic bacteria resistant to many antibiotics (multidrug-resistant strains) have created the need for the development of novel therapeutic agents. Only two new classes of antibiotics of novel mechanisms of action (linezolid and daptomycin) have been introduced into the market during the last three decades. The recent progress in molecular biology and bacterial genome analysis has had an enormous impact on antibacterial drug research. This review presents new achievements in searching a new bacterial essential genes, a potential targets for antibacterial drugs. Application of metagenomics strategy is also shown. Some recent technologies aimed at development of anti-pathogenic drugs such as inhibitors of quorum sensing process or histidine kinases are also discussed. Extensive research efforts have provided many details concerning structure of bacterial proteins playing an important role in pathogenesis such as adherence proteins or toxins, what allowed searching for antitoxin drugs or drugs interfering with bacterial adhesion. As an example, the review focuses on anthrax therapies under development. Additionally, the article presents the progress in phage therapy; using bacteriophages or their products such as lysins in antibacterial therapy.     

我院抗菌药物实行分级管理后使用情况分析

目的:分析抗菌药物分级管理干预措施的实施及效果。方法:选择2011年5月至2013年5月间我院全院出院患者6622例的病案资料。其中实施分级管理制度之前的患者3238例,实施分级管理制度之后的患者3384例,分析分级管理前后医院抗菌药物使用情况。结果:实施分级管理制度后抗菌药物使用率,人均使用频次及人均抗菌药物费用均明显降低,与实施分级管理制度前比较差异具有统计学意义(P0.05)。实施分级管理制度后一线抗菌药物使用率显著提高,二线、三线抗菌药物使用率降低,与实施分级管理制度前比较差异具有统计学意义(P0.05)。实施分级管理后三联用药比例显著降低(P0.05),送检标本及检出阳性率较实施分级管理前无统计学意义(P0.05)。结论:实施抗菌药物分级管理可以有效的限制抗菌药物滥用情况,对于临床抗菌药物合理应用有积极意义。     

Drug discovery targeting cell division proteins,microtubules and FtsZ

Eukaryotic cell division or cytokinesis has been a major target for anticancer drug discovery. After the huge success of paclitaxel and docetaxel, microtubule-stabilizing agents (MSAs) appear to have gained a premier status in the discovery of next-generation anticancer agents. However, the drug resistance caused by MDR, point mutations, and overexpression of tubulin subtypes, etc., is a serious issue associated with these agents. Accordingly, the discovery and development of new-generation MSAs that can obviate various drug resistances has a significant meaning. In sharp contrast, prokaryotic cell division has been largely unexploited for the discovery and development of antibacterial drugs. However, recent studies on the mechanism of bacterial cytokinesis revealed that the most abundant and highly conserved cell division protein, FtsZ, would be an excellent new target for the drug discovery of next-generation antibacterial agents that can circumvent drug-resistances to the commonly used drugs for tuberculosis, MRSA and other infections. This review describes an account of our research on these two fronts in drug discovery, targeting eukaryotic as well as prokaryotic cell division.     

人体共生菌及其抗菌分子研究进展

随着耐药细菌的出现和广泛传播,开发新型抗菌药迫在眉睫。分布在人体不同部位的共生菌能够产生多种抗菌分子以抑制病原菌的定植和感染。人体共生菌的抗菌分子为研发全新结构和作用机制的药物提供了潜在的资源宝库,随着生物信息学、合成生物学、基因组学等组学技术的进一步发展,对人体共生菌抗菌分子的挖掘也会更加深入,为解决耐药问题提供了有效的途径。文中回顾了目前所发现的人体共生菌产生的抗菌分子,并介绍了几种用于挖掘人体共生菌这一天然抗菌药物的资源宝库的方法。随着现代生物工程技术的发展,人体共生菌的抗菌分子将会得到更加全面、系统的探索和应用。     

鲍曼不动杆菌VI型分泌系统溶血素-联合调节蛋白研究进展

鲍曼不动杆菌是一种革兰氏阴性的非发酵致病菌,在医院环境中广泛存在,并且已经成为医院获得性感染的重要病原体之一。近年来,由于抗菌药物的广泛应用,导致多重耐药鲍曼不动杆菌引起的感染和暴发流行,给临床治疗带来了极大的挑战。有研究表明,细菌Ⅵ型分泌系统与细菌的致病性相关。本文综述了鲍曼不动杆菌Ⅵ型分泌系统及主要功能蛋白(溶血素-联合调节蛋白)的研究进展,以期为进一步研究鲍曼不动杆菌的致病机制提供基础。     

An in vivo platform for rapid high-throughput antitubercular drug discovery

Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model's utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.     

取消药品加成对北京市公立医院用药结构的影响

目的 以全身用抗细菌药品为例,定量评估取消药品加成政策对北京市5家试点三级综合公立医院高价药使用变化的效果。方法 构建以药品限定日剂量为度量单位的高低价药品相互替代的用药结构指数分析体系,建立双重差分模型,对取消药品加成政策对北京市三级综合公立医院高价药使用变化的净效果进行评估。结果 取消药品加成政策实施后,5家试点医院中的1家试点医院对高价药的使用显著减少,且差异有统计学意义（P＜0.01）,1家试点医院对高价药的使用变化不明显,3家试点医院对高价药的使用显著增加,且差异有统计学意义（P＜0.05）。结论 取消药品加成政策对北京市5家三级综合公立医院在全身用抗细菌类药品中高价药使用变化的影响效果与不同的医院有关,取消药品加成政策对公立医院减少高价药使用的有效性有待进一步研究。     

嗜盐微生物在生物医药领域的应用研究进展

近年来抗生素耐药性问题日趋严重,患癌人数也在逐年增加,亟需开发新型药物。嗜盐微生物作为一类特殊的极端环境微生物,具有代谢多样性丰富、营养需求较低和能适应恶劣条件等特点,是发现新型药物的希望。目前,国内外学者已从嗜盐微生物中分离出了多种代谢产物和酶,具有明显的抗菌和/或抗肿瘤等活性。文中综述了嗜盐微生物及其相关产物在抗菌、抗炎、抗肿瘤、抗氧化、生物医学材料以及药物载体等生物医学方面的作用,尤其对近年来在嗜盐微生物中发现的新型抗菌和抗肿瘤物质以及嗜盐微生物特有的代谢产物四氢嘧啶等进行了总结,并对其后续在生物医药领域的开发和产业化应用进行了展望。     

Antibacterial Agents in Mediterranean Finfish Farming: A Synopsis of Drug Pharmacokinetics in Important Euryhaline Fish Species and Possible Environmental Implications

The literature pertaining to the use of registered antibacterial agents in Mediterranean finfish farming is reviewed, with an emphasis on the Greek fish-farming industry. This review provides a scientific resource dedicated to the design of future antibacterial dosing regimes in Mediterranean fish farming, where insufficient supporting information is currently available. This paper addresses the paucity in knowledge concerning pharmacokinetics and the efficacy and environmental impact of commonly used antibacterials needed to direct future research and promote good practices in the euryhaline fish farming industry. Several registered antibacterials are currently available for combating bacterial infections, including tetracyclines, (fluoro) quinolones, potentiated sulfa, penicillin and chloramphenicol derivatives. Based on the available data, oxytetracycline (OTC) and quinolone drugs (oxolinic acid – OA and flumequine – FLU) are the most widely used in Mediterranean aquaculture. As a result these drugs have received the most extensive studies, whereas, there is considerable paucity of reliable data on pharmacokinetic and the depletion characteristics of other drugs used, particularly potentiated sulfa, penicillin derivatives and florfenicol. We find there is incomplete data on drug efficacy and minimum inhibitory concentrations (MIC) for common antibacterials used against the major bacterial pathogens of Mediterranean fish species. Furthermore, a considerable lack of data on environmental drug concentrations around Mediterranean fish farms was also identified, highlighting the need for more extensive environmental studies to monitor contamination in environmental components i.e., water and sediment, and in non-target species (flora and fauna). Prudent selection and use of antibacterials can encourage lower dosage applications, enhance treatment efficacy, and help to minimize contamination of the environment. Selection of readily bioavailable drugs which have low environmental persistence, low aquatic toxicity and high antibacterial efficacy is advised, to reduce potential losses to the environment and associated toxic effects on target species and the development of bacterial resistance. Lack of present data made it impossible to provide thorough and accurate guidance on selection and use of antibacterials and approaches for minimizing environmental impacts for the treatment of major euryhaline aquaculture species.     

Hospital formularies: need for continuous intervention.

The effects of introducing a hospital formulary alone and with active intervention were compared prospectively with regard to drug costs and the quality of prescribing. Intervention comprised feedback on prescribing habits, peer comparison, and information on drugs. Aspects of prescribing that were not subjected to intervention did not alter. In the year in which intervention occurred generic prescribing rose by 50%; inappropriate prescribing and overall use of third generation cephalosporins fell; and compliance with the recommended list of drugs was good. Overall, drug costs remained static, compared with a projected increase of 0.25 m pounds; in a comparative control hospital drug costs rose by 18%. During the next year, when no form of intervention took place, previous gains were eroded and drug costs rose. Continuous intervention, review, and feedback are required if a formulary is to continue to achieve its objectives.     

Chemotherapy of Pseudomonas aeruginosa infections in children during the first three months of life]

The data on the efficacy of antibacterial drugs and their combinations in treatment of 150 three-month old infants with generalized infection due to Pseudomonas aeruginosa are presented. The clinical isolates of P. aeruginosa were found to be carriers of multiple drug resistance which markedly complicated the chemotherapy. Only combined antibacterial therapy of such infants proved to be rational. High activity of aminoglycosides, azlocillin and cefotaxime against P. aeruginosa and the synergistic action of their combinations observed in the patients permitted to recommend the use of combinations of the above drugs in the empirical chemotherapy.     

Seventeen years' experience of a voluntarily based drug rationalisation programme in hospital.

A study was carried out analysing the operation of a drug rationalisation programme in a central London teaching district that had evolved from experience over 17 years. Creation of a limited list of about 700 drugs had been achieved by local consensus. Drug selection was based on appraisal of efficacy, safety, and cost and was undertaken by means of collaborative participation of most consultant specialists in the district. Educative and other non-restrictive strategies for reinforcing the rationalisation policy had achieved a consistently high rate of compliance in prescribing recommended drugs. The concept of selectivity in drug use and its continuous local reappraisal had a beneficial impact on the prescribing habits of doctors at all levels of seniority as well as on the training of medical undergraduates and nurses in the therapeutic use of medicines. Peer review and self audit were encouraged by use of an extensive monitoring system which incorporated continuous "facilitative" dialogue between ward pharmacists and prescribers. Two models of drug rationalisation programme were studied, the second of which together with other local initiatives had been associated with substantial and sustained reductions in drug spending each year over nine years since 1978. It is concluded that the second drug rationalisation programme model substantially improves the cost effective use of drugs in hospital and furthermore has the potential of being extended to general practice, especially in types of prescribing that are common to both forms of patient care.     

规范医院抗菌药物临床应用的效果与探索??????? ——以某高校7所附属医院为例

某医学院校从2011年5月起在7所直属医院开展抗菌药物临床应用专项整治工作。通过对药品品种、微生物送检、抗菌药物使用情况等指标的分析,评价工作的效果,并从抗菌药物分级管理、围手术期抗菌药物应用和临床药师的作用等角度谈了体会和建议。     

血清降钙素原(PCT)检测对于老年心衰抗感染治疗的指导意义分析

目的:探讨血清降钙素原(PCT)对于老年心衰患者抗感染治疗中的指导意义。方法:选取我院于2013年1月-2014年6月间收治的130例老年心衰患者,将其随机分为观察组以及对照组,每组65例,对照组根据患者的病情变化决定是否使用抗菌药物,而观察组根据PCT变化决定是否使用抗菌素治疗。比较2组患者的体温、PCT、WBC、CRP变化情况,治疗效果,住院情况以及抗菌素使用情况。结果:观察组在使用抗菌药物当日的PCT水平明显低于入院时,P0.05,而体温、WBC、CRP水平比较无明显差异,使用抗菌药物3 d后,血清PCT水平相比于使用抗菌素当日明显下降,体温相比于入院时显著下降,P0.05。观察组的二重感染率明显低于对照组,P0.05,观察组的抗菌药物使用疗程、费用以及总住院费用均明显低于对照组,组间比较有明显差异,P0.05。结论:PCT指标应用于老年心衰患者应用抗菌素的指导治疗,能够减少抗菌药物的使用量,降低住院费用,减少住院时间,减少二重感染的发生率。     

The use of sedative-hypnotic drugs in a university teaching hospital.

We reviewed the charts of 476 patients admitted to a university teaching hospital to determine whether sedative-hypnotic drugs (SHDs) were being used excessively and to examine the use of SHDs as hypnotics. The frequency of medical and surgical indications for barbiturates and benzodiazepines or other minor tranquillizers as well as the use of such drugs were compared among different groups of patients and specialty wards. Of the patients 29% had a regular order and 40% had a PRN order; only 77% of the PRN orders were administered. A total of 215 patients (45%) received an SHD during their hospital stay, and 160 (34%) received the drug as a hypnotic. Medical indications accounted for 49% of the regular orders but only 2% of the PRN orders; moreover, 89% of all the PRN orders were for insomnia. On average, patients receiving SHDs as hypnotics were older (p less than 0.05) and stayed longer in hospital (p less than 0.01) than those who did not; however, no patient on the geriatric or pediatric ward received an SHD as a hypnotic during the hospital stay. The differences in use between patient groups may have been influenced by orientation of ward staff. Physicians should review their rationale for prescribing hypnotics and avoid routine orders on admission.     

呼吸内科患者白色念珠菌痰培养阳性的危险因素及耐药性变迁分析

目的分析呼吸内科患者白色念珠菌痰培养阳性的危险因素及对常用抗真菌药物的耐药性,为临床预防、早期诊断及有效治疗提供依据。方法对2007年1月至2009年12月浙江大学医学院附属第一医院呼吸内科白色念珠菌痰培养阳性患者的临床资料进行回顾性调查,统计其年龄分布、可能感染因素、基础疾病、被感染前抗菌药物的使用及近3年对抗真菌药物的耐药性变迁。结果呼吸内科白色念珠菌痰培养阳性的相关因素多,老年、气管插管/切开、机械通气、慢性阻塞性肺疾病及长期多种抗菌药物的使用患者中感染几率明显增高,且3年来,白色念珠菌的耐药性有所升高。结论临床上细心操作、抗菌药谨慎使用是目前减少白色念珠菌感染的重要途径。     

感染控制与抗菌药物管理措施干预对骨科手术部位感染的影响

探讨感染控制与抗菌药物管理措施干预对骨科手术部位感染(surgical site infection, SSI)的影响，为有效降低SSI的发生提供循证依据。以2013—2018年在上海市杨浦区中心医院骨科住院的 8 916 例手术患者作为研究对象，其中干预前 2 462 例，干预后 4 636 例，强化干预 1 818 例。采取综合性感染控制集束化管理与抗菌药物管理干预措施，分为干预前(2013—2014年)、干预后(2015—2017年)和强化干预(2018年)3个阶段，主要措施包括术前手卫生及患者准备、术中保温及围术期合理用药等。对骨科SSI情况及干预效果进行评估。结果显示，实施感染控制的集束化措施与有效的抗菌药物管理措施后，手术患者SSI发生率由干预前的1.58%下降至0.61%(P<0.05)。干预前、后及强化干预Ⅰ、Ⅱ类切口预防用抗菌药物的品种合理率分别为54.83%、79.82%和99.04%，时机合理率分别为51.99%、78.53%和89.97%，疗程合理率分别为52.98%、82.19%和91.97%，结果显示抗菌药物品种选择、给药时机及疗程的合理率明显改善(P<0.05)，且平均住院天数及抗菌药物占住院总费用的比例明显下降(P<0.05)，表明长期连续的综合性感染控制与抗菌药物管理干预可有效降低骨科手术患者SSI的发生。