抗生素诱导SPF级BALB/c小鼠胃肠道白念珠菌定植模型

目的:建立抗生素诱导SPF级BALB/c小鼠胃肠道白念珠菌定植模型.方法:SPF级♀Balb/c小鼠随机饮用抗生素头孢曲松水溶液5d(120h)后,单次口服灌胃107CFU(50μL)白念珠菌以诱导其定植.并运用平板计数和基于细菌16SrDNA的PCR-DGGE技术分析小鼠胃肠道的白色念珠菌定植与微生物区系变化.结果:抗生素处理5d后,减少了胃肠道99.99%以上的可培养厌氧菌和肠杆菌,与处理前相比,有极显著差异(厌氧菌:8.53±0.31Log10CFU/gvs4.18±0.90Log10CFU/g,P<0.01;肠杆菌:3.67±0.14Log10CFU/gvs0,P<0.01),而且DGGE图谱分析显示,抗生素处理后小鼠细菌微生物区系的多样性明显减少(条带数由27-32条减少到2-7条).对抗生素处理小鼠单次口服灌胃107CFU白念珠菌2d后,在小鼠胃、小肠、盲肠和大肠检测到大量的C.albicans,数量分别为4.44±0.02Log10CFU/tissue,5.05±0.19Log10CFU/tissue,5.62±0.06Log10CFU/tissue,4.95±0.14Log10CFU/tissue,并且单次口服灌胃白念珠菌1wk后,小鼠胃肠道内仍维持有4.01±0.06Log10CFU/g的白念珠菌定植.与正常Control组和Antibioticonly组相比,Antibiotic Candida模型组小鼠肠杆菌增殖了10到100倍(3.65±0.16Log10CFU/g,3.21±0.18Log10CFU/gvs5.42±0.33Log10CFU/g,P<0.05);同时DGGE图谱分析显示,Antibiotic Candida模型组小鼠细菌微生物区系多样性较低(条带数Antibiotic Candida/22-24条,Control/28-34条和Antibioticonly/27-34条),各小鼠细菌微生物区系之间的相似性为63.8%-67.0%.结论:抗生素处理诱导了胃肠道微生物区系紊乱,导致了白念珠菌在SPF级Balb/c小鼠胃肠道定植成模.     

胸腺肽抗白念球菌感染对小鼠肾和淋巴器官组织学变化的观察

我们观察了正常的和应用免疫药物的小鼠,在接种白念珠菌孢子后的肾脏和淋巴器官的组织学变化。发现淋巴器官变化与白念珠菌在肾脏内生长发育的不同阶段密切相关。认为肾脏内白念珠菌假菌丝的形成和消失,可以影响宿主的细胞免疫功能。因此,如何阻止肾脏内白念珠菌假菌丝的形成是防治小鼠白念珠菌感染的关键。     

免疫抑制小鼠肺白念珠菌感染模型的建立

目的建立免疫抑制小鼠肺部白念珠菌感染模型,为相关的感染研究提供科学依据。方法 ICR小鼠一次性腹腔注射环磷酰胺200 mg/kg,尾静脉采血计数白细胞。鼻滴组小鼠每天经双侧鼻孔滴入浓度为2×109 cfu/ml的白念珠菌悬液40μl;雾化组小鼠每天吸入浓度为2×109 cfu/ml的白念珠菌悬液20 ml,连续感染8 d后处死小鼠,行组织培养和病理学检查。结果环磷酰胺注射后,小鼠白细胞数明显下降。鼻滴组肺组织培养可见乳白色光滑菌落生成,病理切片可见大量炎细胞浸润,肺泡结构紊乱,肺泡腔内可见弥散的红细胞。雾化组培养未见菌落生成,病理表现为炎症反应。结论降低小鼠免疫力,应用鼻滴的方法可以建立小鼠肺部白念珠菌感染模型。     

阴道炎患者感染白念珠菌的耐药性及基因突变研究

目的分离妇科阴道炎患者感染的白念珠菌,检测其耐药性及耐药株基因突变情况,以指导临床合理用药。方法取临床分离的白念珠菌耐药株和敏感株,经传代后再次进行药敏试验,以确定耐药情况。然后提取基因组DNA,进行电泳检测;采用PCR扩增ERG11基因并测序。结果药敏试验显示氟康唑对白念株菌GZ16传代后的MIC值为64μg/ml,判定GZ16为耐药株;SC5314的MIC值为2μg/ml,判定为敏感株;基因组DNA电泳,可见白念株菌GZ16、SC5314两菌株目的条带位于相同位置;对ERG11基因测序,在GZ16白念珠菌有G487T和T916C两个突变位点,SC5314白念珠菌有All67G、A1587G及T462A、T495A、A504G、A530C、C558T、C805T等8个基因位点的突变,并且还存在氨基酸的错义突变,包括:F105L(T462A)、D116E(T495A)、K128T(A530C)。结论分离自妇科阴道炎患者的白念珠菌部分对氟康唑耐药并发生ERG11基因G487T和T916C位点突变,该突变可能与白念珠菌对氟康唑耐药有关。     

白念珠菌的生物形态分型研究

本文报道了首先建立的白念珠菌（白念）的生物形态分型法－型别由５个数字组成的编码表示。１７５株临床分离的白念被分为８５个型,以编码００００２为最常见（占７．４％）,分辨指数为０．９８２。并分析了型别与临床的关系,初步表明菌落条纹与毒力可能有一定关系。该法具有简单、经济、重复性好和分辨率高等优点,适于病原学研究和流行病学调查。     

口腔念珠菌病的诊治

口腔念珠菌病是由真菌—念珠菌属感染所致的口腔粘膜疾病 ,其中白色念珠菌是最主要的病原菌。鹅口疮 (雪口病 )是最常见的口腔念珠菌病。近年来 ,由于抗生素和免疫抑制剂的广泛应用 ,使口腔粘膜念珠菌病的发病率增高 ,长期慢性口腔念珠菌感染尚能引起恶变的可能 ,应引起重视。2 5 %～ 5 0 %健康人的口腔、阴道、消化道可带有念珠菌 ,但不发病 ,与机体处于共生状态 ,属非致病性念珠菌 ,在某种条件下 ,可转变为致病性的。其致病性取决于 :1病原菌的毒性和类型。白念菌为一卵圆形 G 芽生酵母样菌 ,在一定条件下能产生假菌丝 ,酵母型念珠菌无…     

小鼠胃白念珠菌感染动物模型的建立

目的: 通过降低小鼠免疫力并给小鼠胃肠道造成溃疡, 建立小鼠胃白念珠菌感染动物模型.方法: 昆明小鼠110只随机分成3组. 对照组Ⅰ给予浓度5.5×1012白念珠菌菌悬液0.5 mL灌胃; 对照组Ⅱ腹腔内注射浓度40 g/L的环磷酰胺溶液0.02 mL/g体质量, 并用3 g/L冰醋酸溶液0.5 mL灌胃; 模型组用对照Ⅱ组方法灌胃, 2h后给予浓度5.5×1012白念珠菌菌悬液0.5 mL灌胃. 于第10天取小鼠胃组织行真菌镜检、组织病理检查, 同时取所有真菌镜检阳性胃组织经念珠菌显色培养基培养, 观察菌落.结果: 模型组小鼠胃组织内发现念珠菌孢子、芽生孢子、假菌丝及大量成团菌丝. 模型组与对照组Ⅰ真菌镜检及组织病理HE染色阳性率比较有显著性差异(χ2 = 40.763, 40.526,均P<0.01), 与对照组Ⅱ比较也有显著性差异(χ2 = 58.964, 44.074, 均P<0.01).结论: 通过降低小鼠免疫力并造成胃溃疡, 应用白念珠菌感染可以建立小鼠胃白念珠菌感染动物模型.     

经皮气管穿刺法建立家兔白色念珠菌肺炎动物模型

动物模型的建立是研究各种疾病诊断和治疗的先决条件,而目前国内尚无白色念珠菌(下称白念菌)肺炎动物模型的研究。2004年10月,我们通过经皮气管内穿刺法成功建立了白念菌肺炎动物模型。     

不同来源白念珠菌感染小鼠前后胞外水解酶活力差异

目的 了解白念珠菌进入小鼠宿主前后其分泌胞外水解酶能力是否改变。方法 挑选分泌型天冬氨酸蛋白酶、磷脂酶、脂肪酶活力无差异的艾滋病、外阴阴道念珠病病患来源和健康人来源白念珠菌,尾静脉注射感染小鼠,分离发病死亡小鼠肾脏菌株,比较感染小鼠前后菌株胞外水解酶活力差异。结果 不同来源菌株感染的小鼠28 d内死亡速率差异显著(χ²=82.5,P<0.05),从高到低依次为艾滋病、外阴阴道念珠病、健康人来源组;各来源菌株感染小鼠后肾脏分离株分泌型天冬氨酸蛋白酶表达水平皆高于感染小鼠前(F=7.89,P<0.05),不同来源区别显著(F=4.96,P<0.05),从高到低依次为艾滋病、外阴阴道念珠病、健康人来源;感染小鼠前均未曾测得磷脂酶活力的各来源菌株中,在感染小鼠后仅艾滋病、外阴阴道念珠病来源组小鼠肾脏分离株可测得磷脂酶活力,但艾滋病、外阴阴道念珠病来源两组间感染小鼠后肾脏分离株磷脂酶活力无显著差异(F=2.54,P>0.05);各来源白念珠菌感染小鼠前后均未测得脂肪酶活力。结论 在宿主体内白念珠菌表达天冬氨酸蛋白酶、磷脂酶能力相较于体外有增强;在不同宿主环境状态下,白念珠菌分泌型天冬氨酸蛋白酶和磷脂酶的潜在表达能力有差异,即宿主免疫状态越弱时,白念珠菌分泌型天冬氨酸蛋白酶、磷脂酶潜在表达能力越强。     

酵母菌杀菌系统用于白念珠菌分型

本文报道在国内首先建立了酵母菌杀菌系统用于白念珠菌(白念)的分型方法。对175株临床分离的白念分型,型别由3个数字组成的编码表示,175株被分为62个型,以编码511为最常见(占19.4％),分辨指数0.934。初步探讨了杀菌活性的机理,认为杀菌活性是杀菌哮母菌分泌的代谢产物的作用。该法具有简便、快速、结果易判定、重复性好和分辨率高等优点,易在医院实验室推广,且可与形态学分型法联合应用。     

老年肺癌放疗唤起性肺炎2例并文献复习

目的探讨老年人放疗唤起性肺炎的诊断和治疗。方法报告了2例老年肺癌患者放疗后应用靶向药物和抗生素治疗引起放疗唤起性肺炎的诊治过程。结果2例老年肺癌患者均接受放射治疗,在其后续治疗中发生放疗唤起性肺炎,诱导药物分别为厄洛替尼、左氧氟沙星和头孢哌酮舒巴坦。停用诱导药物和加用糖皮质激素治疗后,患者临床症状改善、肺部阴影吸收。结论放疗唤起性肺炎是一种罕见疾病,临床上容易误诊和漏诊,老年肺癌患者在接受放射治疗后的后续治疗中一定要警惕其发生。     

老年药物性肝损伤的临床特点

目的探讨引起老年药物性肝损伤的药物种类、临床特点及防治原则。方法对2005年1月～2009年6月复旦大学附属华东医院160例发生药物性肝损害的老年住院病例临床资料进行回顾性分析。结果药物性肝损害患病率为3．17％（160／5047）;老年患者联合用药多,易出现肝损害,以心血管药物最多,构成比为25．6％（41／160）,其次是抗肿瘤药,构成比为21．9％（35／160）,再次是抗生素,构成比为18．1％（29／160）。主要临床症状为疲乏纳差、恶心呕吐,构成比为39．4％（63／160）,黄疸构成比为8．1％（13／160）,低热构成比为5．6％（9／160）,皮肤搔痒构成比为4．4％（7／160）,无症状者构成比为59．4％（95／160）。临床治愈率为71．3％。结论心血管药、抗肿瘤药和抗生素是引起老年药物性肝损害的常见药物。老年患者肝功能受损后大多无明显症状。老年人肝损伤与其肝药物代谢酶活性降低及长期联合用药有关。     

老年人药物性肝损害88例临床分析

目的 探讨致老年人药物性肝损害的药物种类、临床特点及防治原则。方法 对1998年1月。2001年12月我院老年病科88例发生药物性肝损害的住院病例临床资料进行回顾性分析。结果 药物性肝损害患病率为2．34％，老年患联合用药多，引起肝损害以心血管药物最多(28．41％)，其次是抗肿瘤药(23．86％)，再次是抗生素(18．16％)。主要临床症状为疲乏纳差、恶心呕吐(36．36％)，黄疸(9．09％)，低热(5．7％)，皮肤搔痒(4．5％)，无症状(61．4％)。临床治愈率75％，无一例出现肝衰竭。结论 心血管药，抗肿瘤药和抗生素是引起老年人药物性肝损害的常见药物。老年患肝功能受损后大多无明显症状。老年人肝损害与其肝药物代谢酶活性降低，长期联合用药有关。老年人应定期检测肝功能。     

Pleural Sclerosis for the Treatment of Pneumothorax and Pleural Effusion

Pleural sclerosis is indicated to obliterate the pleural space when one wants to prevent the recurrence of a spontaneous pneumothorax or the reaccumulation of a pleural effusion. Although many different agents ranging from antibiotics to antiseptics to antineoplastics to talc have been advocated, none is ideal. It is interesting that in the era when we are mapping the human genome, the agent most commonly used for pleurodesis is talc. Talc is very inhomogeneous, and the mechanisms by which it produces pleurodesis are unknown. In this review we will discuss the theory and mechanism of pleurodesis, the indications and contraindications for it, the advantages and disadvantages of the agents presently used for it, and our recommendations for the procedure. Accepted for publication: 4 February 1997     

Candida prophylaxis and therapy in the ICU

The incidence of invasive candidiasis in critically ill patients has increased over the past decade and is associated with considerable morbidity and mortality. CANDIDA is identified in up to 17% of ICU patients, with candidemia occurring in ～1%. CANDIDA ALBICANS continues to account for approximately half of the invasive candidiasis cases, with non- ALBICANS CANDIDA species, such CANDIDA GLABRATA, increasing in frequency. Diagnosis of invasive candidiasis is commonly based on blood culture results; however, the sensitivity of blood culture to identify CANDIDA is low. Because early, appropriate therapy has been associated with improved outcomes, antifungal therapy is being implemented in critically ill patients with risk factors for candidemia (prophylaxis). Systemic antifungal therapy is also being utilized in patients at increased risk for invasive candidiasis based on surrogate markers of infection such as colonization (preemptive therapy), or in patients with unresolving sepsis despite appropriate management (empirical therapy). Recent guidelines on the use of antifungal therapy have better identified patients who can be treated with azole derivatives and those who may benefit from echinocandins or polyenes. However, prospective trials are still needed to better identify appropriate therapy for patients at risk for, or with, confirmed invasive CANDIDA infections.     

Effect of antibiotics and anti-cancer drugs on gastrointestinal infections and dissemination by C. albicans in mice inoculated orally with C. albicans

The authors studied the effect of antibiotics, hydrocortisone and anti-cancer drugs on gastrointestinal infections and dissemination by C. albicans in mice inoculated orally with C. albicans. The mice were given orally, vancomycin, amikacin and polymyxin B, and they also were injected with ampicillin and gentamicin. Hydrocortisone, cyclophosphamide (CPA) which causes leukopenia and neutropenia, and methotrexate (MTX) which injures the mucous membrane of the gastrointestinal tract were injected to the mice. In the mice treated with antibiotics and anti-cancer drugs, and inoculated orally with C. albicans, the colony forming units of the feces conspicuously increased. Gastrointestinal candidiasis was frequently observed, particularly at the cardia and the cardio-antrum line of the stomach of these mice. In addition to these sites, gastrointestinal candidiasis was observed at the antrum and the small intestine of the mice injected with MTX. C. albicans was frequently recovered from the livers and lungs of the mice treated with antibiotics and MTX + CPA which cause leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract. It is suggested that the threshold gut population of C. albicans is a determinant for gastrointestinal candidiasis, and that leukopenia, neutropenia and the damage of mucous membrane of the gastrointestinal tract are important factors for dissemination by C. albicans from the primary gastrointestinal lesions.     

Continuation of antibiotics is associated with failure of metronidazole for Clostridium difficile-associated diarrhea

BACKGROUND: Metronidazole is first-line therapy for C. difficile-associated diarrhea primarily because of its low cost relative to vancomycin. Currently, it is unknown which patients will fail metronidazole therapy. Our goal was to prospectively evaluate risk factors for metronidazole failure. STUDY: Included patients had symptomatic C. difficile-associated diarrhea, either mild or severe. Once enrolled, detailed baseline data were gathered. All interviews were performed daily while the patient was in the hospital for up to 14 days. If discharged prior to 14 days, the patient received a follow-up phone call on day 5 and day 14. Enrolled patients were given a daily stool survey to complete. RESULTS: We enrolled 27 patients with C. difficile-associated diarrhea. All patients (10 of 10) who had their offending antibiotic(s) discontinued had symptomatic resolution of diarrhea by day 14 of metronidazole treatment. Conversely, 59% (10 of 17) of patients who remained on antibiotics during treatment had symptomatic resolution by day 14 (P=0.02). The risk ratio for treatment failure was 2.0 (95% confidence interval, 1.29-3.10) in patients who remained on antibiotics. In our treatment group, there would be one additional metronidazole treatment success for every 2.4 patients who discontinued antibiotics. CONCLUSION: Patients who remain on antibiotics while undergoing treatment of C. difficile-associated diarrhea have a high likelihood of treatment failure with metronidazole.     

Use of antibiotics in patients admitted to the hospital due to acute exacerbation of chronic obstructive pulmonary disease (COPD)

BACKGROUND: The purpose of this study was to assess to what extent symptoms and signs of bacterial infection are present and evaluated in patients admitted to the hospital for exacerbation of chronic obstructive pulmonary disease (COPD) in relation to initiation of antibiotic treatment. METHODS: All adult patients (>18 years of age) discharged from a department of internal medicine in Copenhagen in 1997 with a diagnosis of exacerbation of COPD were included in our study and their reports were retrospectively reviewed. Gender, age, number of admissions and length of hospital stay, use of antibiotics and steroids prior to admission, temperature, white blood cell (WBC) count, results of lung auscultation and X-ray examination of the thorax at admittance, and growth of sputum culture and antibiotic treatment in the hospital were all registered. RESULTS: A total of 400 admissions took place. In 104 of them, chest X-ray was compatible with pneumonia, and 99 cases were treated with antibiotics. In 44% of the remaining 296 cases, antibiotics were given. It was found that 25-45% of the patients with very little evidence of infection-i.e. the absence of, or only the presence of, one of the following indicators of infection: fever (temperature>37.5 degrees C), a raised WBC count (>9 billion/l), or crepitation at lung auscultation-were given antibiotics. In cases presenting with two or three of these indicators, 50-75% were given antibiotics. In 85% of the cases, penicillin or a macrolide was the initial antibiotic of choice. The median hospital stay was 6 days for the entire group of patients. CONCLUSION: These data suggest that, in patients with acute exacerbation of COPD, a relatively high number of patients with only weak symptoms or signs of bacterial infection are treated with antibiotics.     

钦州地区儿童急性呼吸道感染抗生素应用的临床分析

目的 探讨钦州地区儿童急性呼吸道感染抗生素应用情况.方法 对钦州地区2258例儿童急性呼吸道感染患者抗生的使用情况以及不同疾病选择不同的抗生素情况进行调查分析.结果 儿童急性呼吸道感染抗生素应用以哌拉西林/他唑巴坦钠、头孢哌酮钠/舒巴坦钠使用率最高,抗生素的使用以一、两联为主;病原体送检率仅为38%,抗生素品种选择不合理占5.4%.结论 钦州地区儿童急性呼吸道感染的抗生素应用率高,病原体送检率低,需加强措施控制.     

Antibiotics differ in their tendency to cause infusion phlebitis: a prospective observational study

Intravenous administration of antibiotics is a known risk factor for infusion phlebitis. We have previously demonstrated differences in cell toxicity for 4 antibiotics. Clinical experience indicates that antibiotics differ in their tendency to cause phlebitis. The present study was done prospectively on 550 patients with 1386 peripheral venous catheters. The incidence of phlebitis was 18.5% with antibiotics and 8.8% without (odds ratio 2.34). Dicloxacillin (odds ratio 5.74) and erythromycin (odds ratio 5.33) had the greatest tendency to cause phlebitis in univariate, multivariate and Cox regression analyses. Benzylpenicillin, cefuroxime and cloxacillin were also associated with a greater risk of phlebitis, whereas ampicillin, imipenem/cilastatin, clindamycin, netilmicin and vancomycin were not. Other risk factors were the site of insertion and age 51-60 y. Medication with warfarin was found to be protective, but not with aspirin. Treatment with low molecular weight heparin reduced the risk of phlebitis, but the difference was not significant. With regard to when antibiotics were given, the day-specific risk increased between Days 1 and 2, but no further on subsequent days. The hypothesis that antibiotics differ in their tendency to cause phlebitis was confirmed.