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.     

A Comparative Study on the Effect of BCG-PSN and Thymopeptides on T-lymphocyte Subsets of Normal and Immunosuppressed Mice

Polysaccharidenucleicacidfractionofbacilluscalmetteguerin (BCG PSN ,SiqikangInjection)andthymopeptidesarenowtwowidelyusedimmunomod ulatorsinclinicalpractice .Theyareusuallyusedasanadjuvanttherapyforvirusinfection ,autoimmunediseasesandneoplasms ,whichhavebeenclinicallyprovedtobeeffective .Somereportsdemonstratedthattheybothcanstimulatetheproliferationanddif ferentiationofT lymphocytes.However ,theexactmechanismshavenotbeenelucidatedyet .InordertocomparetheirmodulatingmechanismsonT lympho c…     

脓汁查抗酸阳性杆菌感染一例报道

患者，王丽莹，女，47岁，患者主诉，左侧乳房始终有一溃疡，并流脓汁，看过好多地方，用过好多抗菌素，始终未治愈。     

医院内下呼吸道革兰阴性杆菌感染59例临床分析

目的：探讨医院内下呼吸道革兰阴性杆菌感染的病原菌谱、药物敏感性及主要危险因素。方法：回顾性分析我院1998年1月～2001年12月医院内获得性下呼吸道感染，所取痰标本行细菌学培养，阳性菌以K—B纸片法行药物敏感性测定。结果：共获73株革兰阴性杆菌，其中，铜绿假单胞菌(28．77％)，克雷伯杆菌(26．03％)，大肠埃希菌(23．28％)等，共同构成我院医院内下呼吸道感染的主要致病菌。基础疾病以气管插管或气管切开机械通气、昏迷、患有慢性阻塞性肺疾病、使用广谱抗生素以及高龄患者是造成医院内感染的主要危险因素。第三代头孢菌素、氟喹诺酮类和氨基甙类抗生素为治疗革兰阴性杆菌的有效抗生素。结论：抵抗力低下、不合理应用抗生素及基础疾病严重是造成医院内下呼吸道感染的主要危险因素。下呼吸道感染以革兰阴性杆菌感染为主。出现多重耐药菌，应根据药敏选择抗生素，必要时联合用药。     

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。     

肠道革兰氏阴性杆菌及孤菌快速鉴定的研究

目的：为寻求肠道G杆菌及弧菌快速鉴定的方法。方法：菌种经增菌及分离培养后，取菌落接种于综合生化培养基，并在综合生化培养基管口悬挂硫化氢和靛基质试纸条。同时以克氏双糖铁培养基作对照，置37℃培养18-24h。取综合生化管培养基，外加测试氧化酶，共获取11项生化指标。结果：对689株不同菌种与综合生化管培养基和常规双糖铁培养的测试结果，符合率为99．97％，(7577/7579)和99．79％(7563/7579)。结论：综合生化管是适合医疗卫生单位微生物实验室的一种快速检验方法。     

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.