碳青霉烯类抗生素的电喷雾质谱裂解规律分析

目的:研究碳青霉烯类抗生素的质谱(MS)裂解特征,探讨该类化合物的MS裂解规律。方法:正离子检测模式下,利用电喷雾三重四极杆MS对4种碳青霉烯类抗生素(亚胺培南、美罗培南、帕尼培南、比阿培南)的[M+H]+离子,以及由其产生的特征碎片离子进行MS/MS及准MS/MS/MS分析。结果:正离子检测模式下,碳青霉烯类抗生素主要以[M+H]+准分子离子形式存在;其裂解行为是离子[M+H]+主要发生四元环裂解反应、脱羧基反应及碳-硫键的裂解反应,产生相应的特征子离子C、D、G、H。结论:该方法可获得碳青霉烯类抗生素的多级MS信息;依靠MS裂解规律,可以对其类似物、衍生物及代谢物进行快速定性鉴别,并为其定量分析提供有力的理论依据。     

临床药师干预前后腹腔镜胆囊切除术围术期预防用抗菌药的使用评价

目的：调查某院实施干预前后腹腔镜胆囊切除术预防用抗菌药（简称＂预防用药＂）的应用情况,为临床合理预防用药提供参考。方法：分别抽取2013年5～6月和2014年5～6月行腹腔镜胆囊切除术患者,分别纳入干预前组（n=80）和干预后组（n=76）,对两组患者的预防用药情况进行统计分析。结果：实施干预后,预防用药率由干预前的100%降至19.7%,预防用药的选药合理率由干预前的12.5%升至73.3%,预防用药时间由干预前的（3.2±0.9）d缩短至（2.1±0.9）d,差异均有统计学意义（P〈0.01）。术后感染发生率无明显变化。结论：该院临床药师干预措施得力,干预效果显著,明显促进了腹腔镜胆囊切除术围术期预防用药合理性。     

解放军175医院特殊使用类抗菌药物的应用分析及管理

目的分析笔者所在医院特殊使用类抗菌药物的应用及管理情况,为合理用药提供参考。方法收集医院信息系统中2011年度特殊使用类抗菌药物的用药信息,采用限定日剂量（DDD）,对限定日剂量数（DDDs）、日用药费用（DDC）、B/A值等指标进行统计分析。结果我院使用的特殊使用类抗菌药物品种占72.22%,以注射剂型为主。不同类别特殊使用类抗菌药物的DDDs及所占比例、DDC等指标变化各不相同,B/A值介于0.29~9.00之间。结论抗菌药物分级管理制度落实不到位。从严引进特殊使用类抗菌药物,加强特殊使用类抗菌药物的用药教育,严格落实抗菌药物分级管理制度。     

基于医嘱数据的肺炎住院儿童肠道微生态制剂应用的疗效分析

目的描述因肺炎住院儿童使用肠道微生态制剂的相关特征,评估肠道微生态制剂的临床应用效果。方法以上海市儿童医院2012年度因肺炎住院儿童的用药医嘱记录为研究对象,描述性统计药物人群暴露量以及抗菌药物、肠道微生态制剂使用率与治疗开始时间,比较肠道微生态制剂治疗前后使用的抗菌药物品种数量、肠道微生态制剂合用及未合用的住院时间、止泻药治疗比例与时间等。结果 2 974人次用药医嘱纳入分析,接受抗感染药物治疗者2 948人次（99.1%）、肠道微生态制剂治疗者1 252人次（42.1%）、合并抗菌药物以及肠道微生态制剂治疗者1 246人次（41.9%）。肠道微生态制剂起始治疗时间中位数为住院的第2天、众数为第1天。合并抗感染及菌群调节治疗者中,使用肠道微生态制剂前抗菌治疗时间中位数为3 d,众数为1 d。肠道微生态制剂使用后抗菌治疗中位数为5 d,众数为4 d;肠道微生态制剂菌群调节治疗时间的中位数、众数均为4 d。肺炎住院儿童中使用止泻药者626人次（21.0%）,主要集中在新生儿组和婴儿组。抗菌治疗合用肠道微生态制剂、未合用肠道微生态制剂的儿童分别有585人次（47.0%）、34人次（2.0%）接受止泻治疗,有显著性差异（P〈0.05）。合用肠道微生态制剂接受止泻治疗时间中位数为4 d,众数为3 d,四分位数Q1、Q3分别为2 d、6 d;未合用肠道微生态制剂接受止泻治疗时间中位数为3 d,众数为1 d,四分位数Q1、Q3分别为1 d、6 d,两组接受止泻治疗的时间没有显著性差异。抗菌治疗合用肠道微生态制剂的住院时间的中位数为7 d,众数为6 d,四分位数Q1、Q3分别为6 d、9 d;未合用肠道微生态制剂的住院时间的中位数、众数均为7 d,四分位数Q1、Q3分别为6 d、9 d,两组住院时间没有显著性差异。结论因肺炎住院儿童首次使用肠道微生态制剂主要在入院第2天,以预?     

Genome Engineering and Modification Toward Synthetic Biology for the Production of Antibiotics

Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products. Here, we review the progress in the development of these genome editing techniques used to engineer new antibiotics, focusing on three aspects of genome engineering: direct cloning of large genomic fragments, genome engineering of gene clusters, and regulation of gene cluster expression. This review will not only summarize the current uses of genomic engineering techniques for cloning and assembly of antibiotic gene clusters or for altering antibiotic synthetic pathways but will also provide perspectives on the future directions of rebuilding biological systems for the design of novel antibiotics.     

Effects of Knowledge,Attitudes, and Practices of Primary Care Providers on Antibiotic Selection,United States

Appropriate selection of antibiotic drugs is critical to optimize treatment of infections and limit the spread of antibiotic resistance. To better inform public health efforts to improve prescribing of antibiotic drugs, we conducted in-depth interviews with 36 primary care providers in the United States (physicians, nurse practitioners, and physician assistants) to explore knowledge, attitudes, and self-reported practices regarding antibiotic drug resistance and antibiotic drug selection for common infections. Participants were generally familiar with guideline recommendations for antibiotic drug selection for common infections, but did not always comply with them. Reasons for nonadherence included the belief that nonrecommended agents are more likely to cure an infection, concern for patient or parent satisfaction, and fear of infectious complications. Providers inconsistently defined broad- and narrow-spectrum antibiotic agents. There was widespread concern for antibiotic resistance; however, it was not commonly considered when selecting therapy. Strategies to encourage use of first-line agents are needed in addition to limiting unnecessary prescribing of antibiotic drugs.     

High Rates of Antimicrobial Drug Resistance Gene Acquisition after International Travel,the Netherlands

We investigated the effect of international travel on the gut resistome of 122 healthy travelers from the Netherlands by using a targeted metagenomic approach. Our results confirm high acquisition rates of the extended-spectrum β-lactamase encoding gene bla_CTX-M, documenting a rise in prevalence from 9.0% before travel to 33.6% after travel (p<0.001). The prevalence of quinolone resistance encoding genes qnrB and qnrS increased from 6.6% and 8.2% before travel to 36.9% and 55.7% after travel, respectively (both p<0.001). Travel to Southeast Asia and the Indian subcontinent was associated with the highest acquisition rates of qnrS and both bla_CTX-M and qnrS, respectively. Investigation of the associations between the acquisitions of the bla_CTX-M and qnr genes showed that acquisition of a bla_CTX-M gene was not associated with that of a qnrB (p = 0.305) or qnrS (p = 0.080) gene. These findings support the increasing evidence that travelers contribute to the spread of antimicrobial drug resistance.     

177株医院感染铜绿假单胞菌的耐药特性探讨

目的 探讨医院感染铜绿假单胞菌(PAE)的标本分布和耐药性,为临床医师合理用药提供实验室依据.方法 细菌培养和鉴定严格按照《全国临床检验操作规程》进行;药敏试验采用K-B法进行.结果 177株铜绿假单胞菌以呼吸道标本中检出率最高占55.4％;其次为脓液标本占13.0％;尿液标本第3位,占12.4％;PAE对亚胺培南、美罗培南、头孢哌酮/舒巴坦耐药率最低为5.6％～6.2％:对磺胺甲噁唑/甲氧苄啶耐药率最高为55.4％;对其他常用抗菌药物均产生不同程度的耐药;临床标本中未发现铜绿假单胞菌泛耐药株.结论 基层医院PAE的耐药率明显低于城市大型综合医院,但医院PAE耐药性已比较严重,有关管理部门应采取有效措施,遏制PAE耐药性快速增长的不良趋势.     

肺炎链球菌基因PBP1a变异:172 SSN→SSV(Asn172Val)

目的:通过对台州地区β-内酰胺类抗生素耐药的肺炎链球菌青霉素结合蛋白基因的研究,分析肺炎链球菌的耐药机制。方法:收集2009年-2010年浙江台州地区63例肺炎链球菌临床株,进行培养、鉴定及药敏试验,并对耐药菌株行青霉素结合蛋白PBPs基因的PCR扩增和氨基酸序列分析。结果:研究结果显示PBP1a基因的变异位点除了以往报道的KTG保守序列之后变异为Thr574Ala,Ser575Thr,Gln57Gly,Phe577Tyr,和STMK保守区的Thr371Ala,本研究中发现172位氨基酸变异SSN→SSV。并且该菌株成高水平耐药。结论:新的氨基酸变异可能进一步降低了S.pneumoniae对β-内酰胺类抗生素的亲和力。     

临床药师对甲状腺手术预防使用抗菌药物干预研究

目的 评价临床药师干预普外科甲状腺手术围手术期抗菌药物应用的效果.方法 分别抽取干预前(2010年1-6月)、干预后(2010年7-12月)医院普外科甲状腺手术患者病历各80份(甲状腺癌和结节性甲状腺肿各占50.00％),对围手术期预防性应用抗菌药物的合理性进行对比分析.结果 经临床药师干预,甲状腺手术患者围手术期预防应用抗菌药物合理性明显改善,药物选择合理率由干预前的11.25％提高至83.75％,用法用量正确率由58.75％提高至72.5％,给药时机正确率由0提高至51.76％,术后用药时间合理率由18.75％提高至75.00％.结论 临床药师对甲状腺手术围手术期预防应用抗菌药物的干预是可行和有效的,合理的干预可以对Ⅰ类切口围手术期预防用药的合理、有效、安全、经济起到积极的作用.