抗生素风险管理体系构建策略

抗生素在给人们带来临床价值的同时也带来风险：耐药菌株的不断出现，神经毒性、肾衰竭、心脏疾病、哮喘等各种不良反应发生。我们可以采取措施来控制抗生素使用风险，建立抗生素使用的量化指标进行定量控制，通过处方系统对抗生素的使用进行监控，依靠药师来监督医生的处方行为，另外还可以对患者进行抗生素使用的教育，使其对潜在的风险有所认识。     

亚抑菌浓度抗生素对细菌耐药性和毒力影响的研究进展

细菌的耐药性和毒力是决定抗生素治疗成败的关键。近年来研究表明亚抑菌浓度抗生素可以诱导细菌耐药并影响细菌的毒力。本文介绍了亚抑菌浓度抗生素产生的来源；阐述了亚抑菌浓度抗生素对细菌耐药性和毒力的影响。亚抑菌浓度抗生素对细菌耐药性的影响涉及了细菌的耐药选择性、生物被膜和持留菌的形成、基因突变、水平基因转移和基因表达；对细菌毒力的影响主要包括细菌的黏附性、运动性和其它毒力因子。以期为畜牧生产中减少和避免亚抑菌浓度抗菌药的产生，减缓和克服细菌耐药性，降低致病菌的毒力提供参考。     

人体肠道菌群中抗生素耐药基因的水平转移研究

抗生素的广泛使用导致环境中出现了大量耐药菌，其携带的耐药基因会通过水平转移在微生物间传播，加重了耐药基因及耐药菌对环境的污染。由于肠道菌群多样性较高且包含多种抗生素耐药基因，人体肠道逐渐成为抗生素耐药基因发生水平转移的适宜场所。抗生素的过度使用容易改变肠道微生物的组成，影响宿主免疫功能，导致定植抗性的丧失，促使外源耐药菌在肠道定植，对人体健康造成潜在风险。影响人体肠道中耐药基因组成的因素多种多样，包括抗生素的使用，食物，饮水等。本文介绍了肠道菌群耐药基因的组成和传播，总结了肠道菌群中抗生素耐药基因的研究方法，并对未来研究重点进行了展望，以增强对人体肠道抗生素耐药基因的认识，并为减少或控制肠道中抗生素耐药性方法的开发提供新思路。     

抗生素废水组合处理工艺进展

抗生素废水是一种有机物含量高、有毒及生化性能差的难降解废水。本文介绍了近几年来经工程实践证明工艺较成熟、处理效果相对较理想的典型抗生素废水处理工艺,给出了各工艺的流程及处理效果,并对其进行了初步的经济分析。     

生物制品中抗生素的使用及残留检测方法

生物制品生产过程中使用抗生素存在其残留物不能被完全清除的风险,从而对人体产生潜在的危害.本文综述了2015版中国药典对抗生素使用的相关规定,归纳了检测抗生素残留的方法(包括培养法、酶联免疫法)及适用的品种,对抗生素残留分析方法研究现状与前景进行了展望.     

稀土元素在光催化降解抗生素中的应用研究进展

摘要：抗生素广泛应用于医疗和农业生产之中,由于传统的废水处理工艺不能够有效地去除废水中的抗生素,导致目前环 境中已经广泛检测到抗生素的存在。为了预防抗生素污染扩散带来的危害,人们投入了大量的资源研究抗生素的去除方法。本 文参考国内外文献总结了近几年稀土元素在光催化降解抗生素中的应用研究情况,深入揭示了稀土元素在光催化降解抗生素应 用中发挥的作用。主要内容包括：稀土元素掺杂、稀土元素参与构建异质结和稀土元素掺杂与异质结共用的光催化降解;稀土 元素应用在光催化降解抗生素中的3种方法的分析对比;对稀土元素应用于光催化降解抗生素的未来展望。     

大气环境中抗生素耐药菌的来源与传播扩散研究进展

摘要：抗生素耐药性日益成为威胁人类健康的重大挑战。目前,抗生素耐药菌在水和土壤中的传播扩散已被广泛研究,但 大气环境中耐药菌的污染现状还鲜有报道。大气作为一种强流动性的耐药菌存储库,可使细菌在空气介质中长时间跨区域传播 扩散,并可直接被人体吸入,从而对人体健康产生严重的危害。本文介绍了大气环境中抗生素耐药菌的国内外研究现状,分析 了大气中耐药菌的来源以及对人体的潜在健康风险,对今后有关大气环境耐药菌的研究重点进行了展望,对正确揭示耐药菌在 空气中的传播扩散具有重要理论意义     

抗生素对污水生物处理系统脱氮性能影响的研究进展

摘要：抗生素在全球范围内广泛使用，产生大量含抗生素的废水。目前，废水常采用生物法进行脱氮。由于抗生素对微生 物具有抑制作用，其对生物脱氮也会产生不同程度的影响。本文主要阐述了抗生素对硝化过程、反硝化过程及厌氧氨氧化过程 的影响以及微生物抵抗抗生素抑制作用的主要机制，并展望了含抗生素废水处理的研究发展方向。     

控制医院内感染的抗生素用药策略

抗生素类药物已经被人们普遍接受,尽管长期使用此类药物对细菌的耐药选择性和耐药菌的泛滥有着不可推卸的责任.然而,抗生素的大量使用还不可否认地导致许多多重耐药菌的传染性和致病性增大,并且可能使医院获得性感染(HAIs)的病例数增加.因此,在遏制HAI发生的工作中应该更加关注对抗生素的管理.     

细菌整体代谢与新抗生素及抗生素增效剂靶标

摘要：抗菌药物的滥用加速了细菌耐药的产生与传播,每年因耐药细菌导致的人口死亡和医疗成本耗费都极为惊人。针对 耐药细菌的新型抗生素研制十分缓慢,自1987年以来没有一类新型抗生素上市。研究抗生素杀菌机制以开发新药或抗生素佐剂 是一种应对耐药细菌的良好策略。目前普遍认同活性氧(ROS)介导细胞死亡是抗生素杀菌的共享途径,抗生素作用于靶标介导 产生原发初级损伤,诱使ROS生成,ROS造成次级细胞损伤并刺激更多ROS生成,形成一种恶性循环,最终ROS累积超过细胞 氧化应激极限、致使细菌死亡。细菌胞内具有用以消除氧化应激压力的专能系统,针对性抑制这些系统可能是快速杀伤细菌的 一个好策略。然而,设计靶向细菌某些代谢节点的新型抗生素或相关佐剂很可能更为简单、有效,生物体代谢是一个巨大的相 互协作网络,关键节点的扰动很容易引起代谢通路的剧烈波动,能引发细菌整体氧化应激状态改变的代谢节点有望成为潜在新 抗生素或抗生素增效剂的靶标。     

饮用水检测中抗生素类标准物质稳定性研究

抗生素标准物质是药品标准物质的重要类别,了解抗生素标准物质的稳定性,有助于使抗生素标准物质定量分析过程准确可靠,对样品检验具有十分重要的意义。选取生活饮用水中检出率较高、具有代表性的5种不同类别的抗生素,使用超高效液相色谱串联质谱法检测并定量。对不同浓度的标准物质溶液以及加标的自来水样品溶液,在4℃冷藏保存条件及常温使用条件的量值稳定性进行评估。研究结果显示,不同溶剂及温度变化对抗生素稳定性的影响程度不同。苯唑西林在冷藏储存条件下可延迟其降解,常温或冷藏储存对磺胺二甲嘧啶、磺胺甲噁唑、氟甲喹、噁喹酸的稳定性影响不大。本研究进行了饮用水抗生素监测工作中抗生素类标准物质的稳定性分析,为确保监测结果的准确性提供参考价值。     

Prevalence and determinants of antibiotic resistance in faecal Escherichia coli among unselected patients attending general practitioners in Southwest Germany

PURPOSE: Widespread use of antibiotics is thought to be the main reason for the world-wide increase in antibiotic resistance. Although a great majority of antibiotics are prescribed outside hospitals, little is known about the prevalence and determinants of antibiotic resistance in the general population. METHODS: Escherichia coli (E. coli) was cultured from and minimal inhibitory concentrations against six commonly prescribed antibiotic substances were tested in 750 stool samples of 484 unselected, consecutive outpatients aged 40-74 years attending general practitioners. Odds ratios (OR) and their 95% confidence intervals (CI) for the association between potential risk factors and the prevalence of antibiotic resistance were estimated using generalised estimating equations. RESULTS: Prevalence of E. coli resistance against ampicillin, doxycycline, cotrimoxazole or quinolones was 24%. Current antibiotic use was strongly associated with antibiotic resistance, adjusted OR: 11.1, 95% CI: 2.3-53, but antibiotic resistance was unaffected by antibiotic use stopped weeks before. Recent hospitalisations were the only other significant predictor of an increased prevalence of resistance. CONCLUSIONS: The strong association between current use of antibiotics and colonisation with antibiotic resistant E. coli suggests a major role for selection of resistant strains while using antibiotics that seem to be quickly reversible, though.     

Evaluation of antibiotic use in a hospital with an antibiotic restriction policy

The study was designed to evaluate rational antibiotic use in relation to diagnosis and bacteriological findings. All hospitalized patients who received antibiotics were evaluated by a cross-sectional study. Of the 713 patients hospitalized, 281 (39.4%) patients received 377 antibiotics. Among 30 different antibiotics the most frequently requested were first generation cephalosporins (19.9%), ampicillin-sulbactam (19.1%) and aminoglycosides (11.7%). Antibiotic use was appropriate in 64.2% of antibiotic requests. In analysis of appropriate use, a request after an infectious diseases consultation was a frequent reason (OR=14, P<0.001, CI=0.02-0.24). Antibiotics requested in conjunction with susceptibility results were found to be more appropriate than those ordered empirically (OR=4.5, P=0.017, CI=0.06-0.76). Inappropriate antibiotic use was significantly higher among unrestricted antibiotics than restricted ones (P<0.001). Irrational antibiotic use was high for unrestricted antibiotics. Additional interventions such as postgraduate training programmes and elaboration of local guidelines could be beneficial.     

抗内毒素抗体治疗严重烧伤内毒素血症29例

目的 研究抗内毒素抗体与抗生素对严重烧伤并发症——内毒素血症的治疗作用。方法29例患者随机分为拮抗内毒素治疗组和常规治疗组。并在烧伤后不同时相点测定了血浆内毒素、血清TNF、血浆IL-6和血浆IL-8的含量。结果抗生素和抗内毒素抗体治疗可明显减少患者血中内毒素水平（P〈0.05），同时降低IL-6，IL-8和TNF血中含量，而单用抗生素治疗对降低血中内毒素水平作用不明显。结论选择合适的抗生素配合抗内毒素抗体的早期应用，是治疗烧伤后内毒素血症及其并发症的有效方法。     

Low sub-minimal inhibitory concentrations of antibiotics generate new types of resistance

Antibiotic resistance is a major threat to modern medicine. Routes of transmission of resistant bacteria are complex and include spread between humans, between humans and animals, between animals and to humans and animals via the environment. Recent findings have shown that resistant bacteria can be selectively enriched even at antibiotic concentrations several hundred-fold lower than previously expected, such as those found in sewage water. In addition, these low concentrations can select for high level resistant bacteria with very low fitness cost in contrast to resistant bacteria selected at high concentrations such as during antibiotic treatment of patients. This calls for action to determine what concentrations and combinations of antibiotics that can be considered safe in waste water and ensure proper measures to reduce the antropogenic contamination with antibiotics.     

某院乳腺肿瘤围手术期抗菌药物使用情况评估及管理对策

目的评估某院乳腺肿瘤围手术期抗菌药物使用情况。方法采用回顾性调查分析方法 ,设计乳腺肿瘤围手术期抗菌药物应用情况调查表,对某院2009年7月～2010年7月出院的乳腺肿瘤患者296份手术病历,进行抗菌药物预防使用的合理性评估、统计分析其围手术期抗菌药物应用情况。结果乳腺肿瘤患者围手术期抗菌药物使用率为100%,术前0.5～2h不用仅术后用抗菌药物、预防用药时间过长、选药不当、无指征联用、选药档次及级别过高等。结论该院乳腺肿瘤围手术期使用抗菌药物尚存在诸多问题,亟待加快实施其针对性的管理对策。     

Stimuli-sensitive drug delivery systems for site-specific antibiotic release

Site-specific delivery of antibiotics has always been a high-priority area in pharmaceutical research. Conventionally used antibiotics suffer several limitations, such as low accumulation and penetration in diseased cells/tissues, limited bioavailability of drugs, drug resistance, and off-target toxicity. To overcome these limitations, several strategies have been exploited for delivering antibiotics to the site of infection, such as the use of stimuli-responsive antibiotic delivery systems, which can release antibiotics in a controlled and timely fashion. These stimuli can either be exogenous (light, magnetism, ultrasound, and electrical) or endogenous (pH, redox reactions, and enzymatic). In this review, we present a summary of recent developments in the field of stimuli-based targeted drug delivery systems for the site-specific release of antibiotics.     

The magnitude and time course of changes in mycophenolic acid 12-hour predose levels during antibiotic therapy in mycophenolate mofetil-based renal transplantation

There is increasing evidence that monitoring predose plasma levels of mycophenolic acid (MPA) is of benefit in renal transplant recipients treated with mycophenolate mofetil (MMF). Concomitant treatment with oral antibiotics leads to a 10% to 30% reduction in MPA area under the curve (AUC)0-12, probably by reducing enterohepatic recirculation (EHR). Because of the timing of EHR (6 to 12 hours postdose), the magnitude of predose MPA level reduction may be disproportionately larger than that of AUC0-12. However, changes in predose MPA levels and the time course over which these changes occur and resolve during antibiotic treatment have not been studied. The purpose of this study was to define the extent and time course of MPA predose level reduction during antibiotic therapy. A total of 64 MMF-treated renal transplant recipients (with tacrolimus cotherapy) were prospectively studied. Clinically indicated cotherapy with either oral ciprofloxacin or amoxicillin with clavulanic acid resulted in a reduction in 12 hour predose MPA level to 46% of baseline within 3 days of antibiotic commencement. No demographic or biochemical variables were associated with the magnitude of MPA level reduction. No further fall in MPA level was seen by day 7, but MPA levels recovered spontaneously to 79% of baseline after 14 days of antibiotics. Levels normalized within 3 days of antibiotic cessation. No changes in daily MMF dose (normalized for body weight) were made during antibiotic treatment. This data should help the clinician to recognize the extent of MPA predose level reduction during antibiotic therapy, and to avoid inappropriate MMF dose escalation and potential risk of toxicity.