替加环素联合5种抗菌药物对多重耐药鲍曼不动杆菌的体外活性

目的 评价替加环素分别联合5种临床常用抗不动杆菌属抗菌药物对57株多重耐药鲍曼不动杆菌的体外抗菌作用.方法 琼脂棋盘稀释法测定替加环素分别联合美罗培南、阿米卡星、环丙沙星、粘菌素、舒巴坦对57株对美罗培南、阿米卡星、环丙沙星、米诺环素均耐药的多重耐药鲍曼不动杆菌的最低抑菌浓度(MIC),并计算部分抑菌浓度指数(FICI).结果 替加环素与5种抗菌药物联合后表现为协同或不相关作用,其中协同率较高的组合为替加环素+阿米卡星组,50.9％;其次为替加环素+美罗培南组,29.8％,未发现拮抗现象.结论 替加环素与5种抗菌药物联合对本组多重耐药鲍曼不动杆菌主要表现为不相关作用,但与阿米卡星联合具有相对较高的协同率.     

耐碳青霉烯鲍曼不动杆菌的体外联合药敏试验研究

目的：对耐碳青霉烯鲍曼不动杆菌进行体外联合药敏试验,寻找有效的抗菌药物组合。方法：选取临床分离的耐碳青霉烯鲍曼不动杆菌株72株,采取棋盘法设计微量肉汤稀释法进行抗菌药联合体外抑菌试验,判断抗菌药联合应用效应。结果：头孢哌酮/舒巴坦与利福平、米诺环素、美罗培南联合应用及米诺环素与美罗培南联合应用对耐青霉烯鲍曼不动杆菌的抗菌效应主要表现为协同和相加作用;头孢哌酮/舒巴坦与左氧氟沙星联合应用主要表现为无关作用,小部分表现为协同和相加作用。结论：建议对耐碳青霉烯鲍曼不动杆菌引起的院内感染,可联合应用头孢哌酮/舒巴坦和米诺环素、利福平、美罗培南或者联合应用米诺环素和美罗培南进行治疗。     

安徽省淮南地区鲍曼不动杆菌耐药性检测

目的 了解淮南地区临床分离鲍曼不动杆菌对临床常用抗生素的耐药性,指导临床合理使用抗生素.方法 选择淮南地区3家医院2010年10月至2012年6月临床分离鲍曼不动杆菌160株,应用生物梅里埃公司的VITEK32全自动微生物分析系统进行细菌鉴定和药物敏感试验,头孢哌酮/舒巴坦药敏试验使用纸片扩散法检测.结果 鲍曼不动杆菌对10种抗菌药物耐药率高于50.0％,其中对氨曲南的耐药率达到90.1％;仅对4种抗菌药物耐药率低于50.0％,其中对头孢哌酮/舒巴坦耐药率最低,为23.4％,其次为亚胺培南和美罗培南,耐药率分别为26.0％和31.2％.结论 淮南地区临床分离的鲍曼不动杆菌耐药和多重耐药现象严重,头孢哌酮/舒巴坦和亚胺培南可做为临床鲍曼不动杆菌感染治疗的首选药物.     

122株鲍曼不动杆菌药敏实验分析

目的 了解鲍曼不动杆菌的耐药性，耐药特点，指导临床合理用药。方法 对应用K-B纸片琼脂扩散法检测的2001年122株鲍曼不动杆菌药敏试验进行统计分析。结果 鲍曼不动杆菌对所测的13种抗生素中，亚胺培南耐药率最低为0%，其次是头孢哌酮/舒巴坦为10%，其他抗生素耐药率均在43%-100%之间，结论 鲍曼不动杆菌对多种抗生素耐药现象严重，而亚胺培南和加酶的抗生不比对鲍曼不动杆菌仍保持较高的抗菌活性。     

产AmpC酶鲍曼不动杆菌的耐药表型及基因型分析

目的通过对鲍曼不动杆菌产AmpCβ-内酰胺酶的耐药表型及基因型分析,研究其耐药特征和流行趋势。方法收集2010年1月至10月两所综合性医院临床分离的多重耐药鲍曼不动杆菌63株,采用琼脂扩散法进行药物敏感试验,采用聚合酶链反应检测AmpC酶。结果 63株鲍曼不动杆菌耐头孢西丁61株(96.8%),而且对临床其他常用抗生素的耐药率也非常高,均在90%以上(除亚胺培南,美罗培南,米诺环素,阿米卡星,头孢哌酮/舒巴坦,替卡西林/棒酸),表现为多重耐药,其中对米诺环素的敏感率最高为56%,头孢哌酮/舒巴坦位列第二为41.3%。所测63株鲍曼不动杆菌中AmpC酶阳性率为67%。结论鲍曼不动杆菌多重耐药有蔓延趋势,出现1株对临床现有抗生素全部耐药的菌株。AmpC酶在鲍曼不动杆菌的耐药机制中起重要作用,其携带率为67%。米诺环素和头孢哌酮/舒巴坦是目前本地区最为有效的抗菌药物。     

我院2011年抗菌药物联用对耐亚胺培南鲍曼不动杆菌的体外抗菌活性分析

目的：对我院耐亚胺培南鲍曼不动杆菌的分布与耐药性进行分析,并检测头孢哌酮／舒巴坦和米诺环素联用对其的抗菌活性,为临床治疗提供合理用药依据。方法：收集我院2011年住院患者各类标本中分离出的142株非重复的耐亚胺培南鲍曼不动杆菌,采用Micro Scan Walk Away 40微生物分析仪进行菌株鉴定和药敏试验,部分药物及联用药敏试验采用K-B纸片法。结果：2011年我院耐亚胺培南鲍曼不动杆菌占鲍曼不动杆菌的80．7％,检出率最高的标本是痰（78．9％）,其次为伤口分泌物（7．7％）。耐亚胺培南鲍曼不动杆菌分布广泛,ICU检出率最高（45．8％）,其次为神经外科（14．1％）、呼吸科（12．0％）。耐亚胺培南鲍曼不动杆菌对头孢哌酮／舒巴坦的耐药率最低（12．0％）,其次为米诺环素（31．7％）。头孢哌酮／舒巴坦和米诺环素联合对耐亚胺培南鲍曼不动杆菌的抗菌活性以协同和相加作用为主,二者无拮抗作用。结论：耐亚胺培南鲍曼不动杆菌耐药严重,为多重耐药菌株。临床在治疗鲍曼不动杆菌引起的感染时,应慎用碳青霉烯类抗生素,以免耐亚胺培南鲍曼不动杆菌的产生及扩散;建议使用头孢哌酮／舒巴坦和米诺环素联合治疗。     

某医院 8年间鲍曼不动杆菌耐药与抗菌药物用量的相关性分析

目的分析某医院住院病人鲍曼不动杆菌耐药率和抗菌药物用量之间的关系,为临床合理用药和控制细菌耐药提供参考依据。方法采用回顾性调查方法,对华中科技大学同济医学院附属协和医院 2010年 1月至 2017年 12月住院病人常用抗菌药物的使用强度及鲍曼不动杆菌耐药率进行统计,并采用 SPSS 23.0统计软件对其进行 Spearman相关性分析。结果 8年共检出鲍曼不动杆菌 10 885株,除米诺环素、替加环素、多黏菌素 B及头孢哌酮舒巴坦外,对常用的 16种抗菌药物耐药率均已高达 80％左右。鲍曼不动杆菌对替加环素的耐药率与其抗菌药物使用强度高度正相关( r＝0.994,P＝0.006);对美罗培南耐药率与其使用强度呈中度正相关( r＝0.717,P＝0.045);对哌拉西林 /他唑巴坦的耐药率也与其使用强度呈中度正相关( r＝ 0.791,P＝0.019)。结论鲍曼不动杆菌的耐药率与替加环素、美罗培南、哌拉西林 /他唑巴坦用量存在中 -高度相关性,应加强这些药物的临床合理应用管理,遏制和延缓医院鲍曼不动杆菌耐药率的增长。     

临床分离的醋酸钙鲍曼复合不动杆菌耐药性分析

目的:研究无锡市第四人民医院和无锡市第三人民医院临床分离的醋酸钙鲍曼复合不动杆菌的耐药情况及其临床分布特点.方法:收集并分离临床来源的35株醋酸钙鲍曼复合不动杆菌,观察并记录临床分布,并用琼脂二倍稀释法测定抗菌药物对醋酸钙鲍曼复合不动杆菌的MIC值.结果:临床分离的35株醋酸钙鲍曼复合不动杆菌ICU感染居多,占42.86%,老年男性居多,主要来源于痰,占88.57%.醋酸钙鲍曼复合不动杆菌对氨苄西林、哌拉西林、头孢唑林、呋喃妥因的耐药率均为100%;对氨苄西林/舒巴坦、阿莫西林/克拉维酸、头孢米诺、头孢匹胺、氨曲南和庆大霉素的耐药率＞90%;对替卡西林/克拉维酸、头孢曲松、头孢吡肟、环丙沙星、左氧氟沙星、复方磺胺甲噁唑的耐药率≥80%;对哌拉西林/他唑巴坦、头孢他啶、阿米卡星、妥布霉素、加替沙星的耐药率＞50%;对亚胺培南、美罗培南、头孢哌酮/舒巴坦的耐药率相对较低,分别为23.53%、11.43%、11.43%.结论:醋酸钙鲍曼复合不动杆菌对美罗培南、亚胺培南、头孢哌酮/舒巴坦较敏感,临床医生应根据药敏结果和患者自身情况合理用药.     

2012-2015年鲍曼不动杆菌耐药性变迁及抗菌药物选择

目的：通过分析鲍曼不动杆菌的耐药性变化,为临床治疗鲍曼不动杆菌感染遴选适宜的抗菌药物。方法：采用VITEK-2 COMPACT全自动细菌鉴定仪进行分离鉴定,按CLSI推荐的K-B法及CLSI 2014年标准判定细菌耐药性,对某院2012-2015年临床分离的鲍曼不动杆菌的分布与耐药性变化进行回顾性分析。结果：鲍曼不动杆菌的分离率和耐药率呈上升趋势,但多重耐药鲍曼不动杆菌的分离率呈下降趋势。该菌大多数分离自痰液和支气管吸出物,检出率最高的科室是ICU病房。近4年来鲍曼不动杆菌对大多数常用抗菌药物的耐药率较高且保持稳定,对以前敏感率高的头孢哌酮舒巴坦、米诺环素、美罗培南的耐药率呈上升趋势。结论：应加强鲍曼不动杆菌的耐药监测,合理使用抗菌药物,可选择多黏菌素E、含舒巴坦复合制剂、米诺环素和替加环素等。     

2010年住院患者鲍曼不动杆菌的耐药性分析

目的了解我院住院患者的鲍曼不动杆菌的分布特点及耐药情况,为临床治疗提供可靠依据。方法采用法国生物梅里埃公司VITEK 2 Compact系统进行细菌鉴定,K-B法进行药敏试验,使用WHONET 5.4软件进行细菌的耐药性分析。结果我院鲍曼不动杆菌检出率为6.62%,出现最多是痰标本,占81.16%;鲍曼不动杆菌感染主要以康复科、神经科及ICU最多,其次为呼吸内科。该菌对头孢哌酮/舒巴坦和米诺环素的敏感性最高,均在80%以上,对美洛培南和亚胺培南的敏感率均在60%以上,对其它抗菌药物的耐药率在50%以上。结论鲍曼不动杆菌是医院感染重要的条件致病菌,其对抗生素耐药率高,且多重耐药,美洛培南和亚胺培南是首选的经验性治疗鲍曼不动杆菌的药物,头孢哌酮/舒巴坦和米诺环素是治疗鲍曼不动杆菌最敏感的抗菌药物,对于多重耐药鲍曼不动杆（MDR-AB）感染,可采用头孢哌酮/舒巴坦和米诺环素联合治疗方案。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.