氨基糖苷类抗生素的发展历程

抗生素的定义，首先来自于20世纪40年代链霉素的发现。在随后的几十年中，其他氨基糖苷类抗生素家族被大量发现并广泛应用，一度成为抗革兰阴性菌感染的首选抗生素。但由于其毒副作用较大，并且细菌对其不断产生耐药性，加上其他结构类别的新型抗生素的不断发现，使其一度几乎退出历史舞台。然而随着多重耐药细菌引起的感染率急剧上升，人们开始关注氨基糖苷类抗生素作为几种重要的治疗革兰阴性病原体的方案之一，并且发掘了其在治疗感染性疾病、艾滋病和遗传性疾病的潜力，使这个“老牌”抗生素重焕生机。     

Impact of ceftazidime restriction on gram-negative bacterial resistance in an intensive care unit

The present study included three periods: (1) a 12-month prerestriction and control period in 2001; (2) a 12-month restriction period with reduced ceftazidime prescribing in favor of piperacillin-tazobactam (2002); (3) and a 24 month postrestriction period (2003–2004). Note that, for results, P represents the difference between 2002 and 2001; P′, the difference between 2003 and 2001; and P″, the difference between 2004 and 2001. No changes in hygiene practices were observed during these three periods. The purpose of this study was to assess the effect of reducing ceftazidime use in an intensive care unit (ICU) upon Gram-negative bacterial resistance, particularly as regards Pseudomonas aeruginosa. During the three periods of the study, patients were similar concerning age, Simplified Acute Physiology Score (SAPSII), the site of nosocomial infection, and the requirements for mechanical ventilation (75% in 2001, 76% in 2002, 74% in 2003, and 85% in 2004). The most commonly isolated pathogens were P. aeruginosa, Acinetobacter baumannii, and Enterobacteriaceae. The use of ceftazidime decreased significantly from 12.6% in 2001 to 9% in 2002, to 3% in 2003 (P′ = 0.0009), and 2.6% in 2004 (P″ = 0.0001) in favor of piperacillin-tazobactam (0% 2001 to 3.7% in 2003; P′ = 0.002; and 5% in 2004; P″ = 0.0001). Simultaneously, we observed a significant decrease in isolates of P. aeruginosa resistant to piperacillin-tazobactam (P = 0.03; P′ = 0.004; P″ = 0.009), and those resistant to imipenem in 2003 (P′ = 0.008). We also noted a significant decrease in A. baumannii isolates resistant to ceftazidime (P′ = 0.01; P″ = 0.0004) and those resistant to imipenem in both 2002 and 2004 (P = 0.03; P″ = 0.04), and a considerable decrease in isolates of Klebsiella pneumoniae producing expanded spectrum betalactamase (ESBL) in 2003 and 2004 (P′ = 0.04; P″ = 6.10⁻⁵). In contrast, we noted an increase in penicillinase-producing isolates of K. pneumoniae, from 6% in 2001 to 16% in 2002 (p = 0.01), 20% in 2003 (P′ = 0.001), and 32% in 2004 (P″ = 10⁻⁶). We concluded that restriction of ceftazidime use was demonstrated to be efficient in reducing antimicrobial resistance, especially to K. pneumoniae ESBL.     

我院2000-2004年医院感染革兰阴性杆菌耐药性趋势的研究

[目的]了解2000年～2004年院内感染革兰阴性杆菌分布及其耐药性。[方法]主要使用MicroScan-4微生物鉴定及药敏仪对2000年1月～2004年12月引起院内感染革兰阴性杆菌进行鉴定及药物敏感试验，结果录入Whonet5．3软件进行分析、统计。[结果]5年间，革兰阴性杆菌所致医院感染中，大肠埃希菌比例最高，在32．8％～38．1％之间，阴沟肠杆菌、不动杆菌比例呈上升趋势。细菌的耐药率在逐年上升，其中阴沟肠杆菌和鲍曼不动杆菌，耐药性高于其它革兰阴性杆菌（P〈0．05），对第三代头孢菌素耐药率分别达到60％～80％、40％～70％。对亚胺培南耐药的菌株日益增多。[结论]细菌的耐药性逐渐增强，阴沟肠杆菌、鲍曼不动杆菌成为非常重要的医院感染病原菌，医务工作者要重视医院感染，加强耐药性监测，合理使用抗生素。     

革兰阴性病原菌耐药性变化的分析

目的：了解革兰阴性病原菌耐药水平的变化趋势。方法：对我院1998～2004年从各类临床标本分离出的革兰阴性病原菌的药敏试验结果进行统计分析。结果：病原菌对亚胺培南的总体敏感率始终保持在较高水平,以下依次为头孢他啶(69%)、阿米卡星(66%)和环丙沙星(66%),但是铜绿假单胞菌和不动杆菌对常用抗生素的敏感率呈下降趋势。大肠杆菌、肺炎克雷伯菌和阴沟肠杆菌对亚胺培南的敏感率始终维持很高水平,但对其它各类药物的敏感率大多呈现明显的下降趋势,或维持在较低水平。结论：革兰阴性病原菌耐药水平有增高的趋势。亚胺培南可作为重症患者经验用药的首选药物之一,慎重使用第3代头孢菌素,并尽量避免经验用药。     

Fine-needle aspiration cytology diagnosis of tuberculosis

Fine-needle aspiration cytology of lymph nodes and extranodal swellings in 160 cases showed granulomatous reaction with or without caseation necrosis in 83%. The material was acellular or predominantly composed of necrotic material, polymorphs, and lymphocytes in 17%. The age of the patient ranged from 1.5 to 72 yr. The male to female ratio was 1:1.3. Acid-fast bacilli (AFB) could be demonstrated in 40.6% of cases. In cases associated with cellular reaction and necrosis. AFB positivity was 50.0%, while it was 66.7% in cases with acellular necrotic material.     

An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region

Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A. These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies. Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible. The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating. The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies. Another possible application is the large-scale screening of blood-bank sera in order to find samples with a high anti-core antibody content.     

Sequential Measurements of Chemokines in Urosepsis and Experimental Endotoxemia

Chemokines are a superfamily of small chemotactic proteins. While increased levels of interleukin-8 have been measured in serum and urine during urinary tract infection, little is known about other chemokines in this condition. Monocyte chemoattractant protein (MCP)–1, macrophage inflammatory protein (MIP)–1, MIP-1 and interferon- inducible protein (IP)–10 were measured in 30 patients with culture-proven urosepsis during a 3-day follow-up and in 11 healthy humans after intravenous injection of endotoxin (4 ng/kg). Urine and serum levels of MCP-1, MIP-1, and IP-10, but not of MIP-1, were elevated in patients on admission, and decreased after initiation of antibiotic treatment. Endotoxin administration to healthy subjects induced increases in plasma and urine concentrations of all four chemokines. These data indicate that clinical and experimental gram-negative infection in humans is associated with enhanced production of chemokines that act mainly on mononuclear cells and that these chemokines are at least in part locally produced.     

Pneumonien bei akuten Leukämien

Summary Acute leukaemia was complicated by pneumonia in 38 (34.8%) of 109 patients treated between 1979 and 1983; in 39.5% of the patients pneumonia occurred more than once. In 23 patients (60.5%) pneumonia occurred during cytostatic therapy, and 25 patients (65.8%) had less than 1000 mm² granulocytes. Antibiotic therapy had no or only little effect in 70%. A total of 21 patients (55.3%) died of pneumonia. In 15 patients a direct relationship could be seen between pneumonia and the bacterial spectrum in the sputum. A prevalence of gram-negative bacteria was found (24 of 40 bacteria isolated, especially Enterobacteriaceae (19). Fungi were cultivated in 10 cases. Each of the typical pneumonia bacteria was only seen once respectively. It is most important that therapy begin immediately, even before the bacteria have been identified. Only then is there hope that the survival time of patients with acute leukaemia can be influenced.

     

儿童医院重点部门耐碳青霉烯类革兰阴性杆菌主动筛查结合集中安置干预效果评价

 目的 对耐碳青霉烯类革兰阴性杆菌（CR-GNB）进行主动筛查,结合筛查结果对患者进行集中安置,评价干预措施的效果,为CR-GNB医院感染防控提供科学依据。方法 选取2017年1月—2018年12月入住某儿科医院重点部门［新生儿、新生儿重症监护病房（NICU）、儿童重症监护病房（PICU）、血液科］患者为研究对象,并对所有患者进行医院感染实时监测。2017年对住院患者入院后48 h及住院期间每周进行一次CR-GNB主动筛查（咽拭子和肛拭子）,2018年1月开始对主动筛查及临床送检CR-GNB阳性患者开展集中安置措施,比较CR-GNB主动筛查率和定植率、集中安置率以及医院感染率的变化。结果 2018年重点部门咽拭子和肛试子CR-GNB主动筛查率较2017年增加（P<0.05）。新生儿室集中安置率最高（97.8%）,其次为NICU（88.9%）,PICU集中安置率最低（47.7%）。2018年重点部门CR-GNB定植率在住院3、7 d后呈下降趋势（P<0.05）。2018年CR-GNB医院感染率较2017年有所下降（P<0.05）,其中新生儿室和NICU患者耐碳青霉烯类肠杆菌目细菌（CRE）医院感染率下降明显,PICU患者耐碳青霉烯类鲍曼不动杆菌（CRAB）和耐碳青霉烯铜绿假单胞菌（CRPA）医院感染率下降明显。CR-GNB主动筛查定植菌和CR-GNB医院感染病原菌均以耐碳青霉烯类肺炎克雷伯菌（CRKP）为主（44.0% VS 51.7%）。结论 CR-GNB主动筛查结合患者集中安置干预措施能够降低CR-GNB定植率,并有效降低CR-GNB医院感染率。     

耐碳青霉烯革兰阴性杆菌耐药性及耐药基因blaKPC的分子特征

目的 探讨耐碳青霉烯类革兰阴性杆菌的临床耐药性及耐药基因blaKPC的分子特征。方法 分析2017年1月-2018年12月某院临床检出的耐碳青霉烯类革兰阴性杆菌。通过WHONET 5.6软件对药物敏感试验数据进行统计分析,采用PCR检测碳青霉烯耐药基因blaKPC、blaNDM、blaIMP、blaVIM、blaOXA-48,对PCR阳性产物进行DNA测序,分析耐药基因的分子结构特点。结果 共收集510株耐碳青霉烯类革兰阴性杆菌,其中耐碳青霉烯类肠杆菌科细菌（CRE）420株,耐碳青霉烯非肠杆菌科细菌90株。菌株主要来自重症监护病房（ICU）、神经外科和呼吸科,分别占60.8%、11.8%、5.3%;标本来自痰、脓性分泌物、静脉血、无菌中段尿,分别占66.9%、8.8%、8.2%、6.5%。耐碳青霉烯类革兰阴性杆菌对常用抗菌药物具有较高的耐药性。PCR结果显示,420株CRE中blaKPC、blaNDM、blaIMP的阳性率分别为54.3%（228/420）、1.2%（5/420）、1.4%（6/420）,未检测出blaVIM和blaOXA-48基因,其中肺炎克雷伯菌、产气肠杆菌、大肠埃希菌分别占携带blaKPC CRE的83.8%、11.8%、2.6%;其他少见菌种中也检出blaKPC基因。非肠杆菌科细菌中仅有2株鲍曼不动杆菌检测出blaKPC。DNA测序结果显示,174株携带blaKPC的菌株中173株检测为blaKPC-2、1株检测为blaKPC-1。结论 该地区耐碳青霉烯类革兰阴性菌以CRE为主,其中以携带blaKPC-2的肺炎克雷伯菌占绝对优势,其他菌株中也均有发现。提示临床需重点加强耐碳青霉烯类肺炎克雷伯菌的监测及预防,防控blaKPC的传播流行。