血流感染高致病性肺炎克雷伯菌毒力因子及分子分型特点分析

目的研究血流感染高致病性肺炎克雷伯菌的毒力基因和基因分型特点。方法采用PCR方法检测临床分离株血流感染高致病性肺炎克雷伯菌的高毒力基因,并进行荚膜血清型和ST分型;采用微量肉汤稀释法通过BD Phoenix全自动细菌鉴定/药敏系统对分离菌株进行药敏试验;应用加克拉维酸复合药(头孢他啶/克拉维酸或头孢噻肟/克拉维酸)与单药(头孢噻肟或头孢他啶)的药敏纸片组合进行肺炎克雷伯菌产ESBLs的表型确证试验。结果 115株血流感染肺炎克雷伯菌临床分离株分为高毒力肺炎克雷伯菌(Hvkp,占43.48%,50/115)和非Hvkp(non-HvKP,占56.52%,65/115)。与non-HvKP相比,HvKP更容易表现为高黏液性表型(44.00%VS 6.15%,P0.01),且普遍携带rmpA(98.00%VS 4.61%,P0.01)、rmpA2(50.00%VS 3.08%,P0.01)、wcag(24.00%VS 2.15%,P0.05)毒力基因。HvKP常为K1、K2荚膜血清型,non-HvKP常为K-nontypable血清型。本组血流感染肺炎克雷伯菌主要流行ST型别为ST23、ST65、ST37,其中Hvkp流行型为ST23、ST65和ST86。Hvkp对常用抗生素的敏感性好于non-HvKP,其中发现产ESBLs耐药hvKP菌株4株。结论血液感染高毒力肺炎克雷伯菌易表现为高黏液性表型且普遍携带rmpA毒力基因,因此应注意检测肺炎克雷伯菌黏液性状、荚膜血清型、毒力基因以及ST分型,以利于hvkp感染的识别。     

高毒力肺炎克雷伯菌肺脓肿临床特征及菌株微生物学特征研究

目的:研究高毒力肺炎克雷伯菌（Hypervirulent Klebsiella pneumoniae,hvKP）肺脓肿的临床特征及菌株微生物学特征,并与经典肺炎克雷伯菌（ Classic Klebsiella pneumoniae,cKP）肺脓肿进行比较。 方法:选取2017年1月至...     

1株高毒力型肺炎克雷伯菌临床分离株毒力及耐药性分析

目的对1株临床分离的高毒力型肺炎克雷伯菌菌株进行毒力基因及耐药基因分析,为临床复杂肺炎克雷伯菌感染的诊断及抗生素使用提供参考。方法首先使用PCR方法对该菌株进行血清学分型、毒力基因和耐药基因检测,然后利用二代和三代高通量测序平台对该菌株进行全基因组测序和序列拼接,应用生物信息学方法全面分析该菌株毒力基因及耐药基因。结果该菌株血清型为K1型,采用PCR方法发现该菌株携带wabG、uge、kfuBC、aerobactin、rmpA、magA和fimH 7个毒力基因及超广谱β-内酰胺酶耐药基因(基因型为SHV型)。高通量测序进一步发现该菌株的基因组还携带clbB、iroC和rffG 3个毒力基因。结论该肺炎克雷伯菌临床分离株血清型为K1,除了携带喹诺酮类和β-内酰胺类耐药基因外,还含有多种毒力基因,增加了治疗难度。全面分析感染菌株携带的毒力基因和耐药基因,有针对性地选择抗生素,可提高抗感染治疗的效率,减少并发症的发生。     

黄芩素联合两性霉素B对烟曲霉菌生物被膜的体外作用

目的探讨黄芩素联合两性霉素B(AMB)对烟曲霉菌生物被膜的破坏作用和杀菌效果。方法采用微量液基稀释法测定黄芩素及AMB对烟曲霉菌的最低抑菌浓度(MIC)及最低杀菌浓度(MFC);构建烟曲霉菌菌株生物被膜模型,将模型分为空白组、黄芩素组、AMB组、黄芩素+AMB组。成模24 h加入黄芩素组、AMB组、黄芩素+AMB组分别加入相应药物干预(黄芩素浓度128μg/m L,AMB浓度8 g/m L),空白组不干预。药物干预48 h后,结晶紫染色法行生物被膜半定量观察,胞外基质染色法荧光显微镜下观察生物被膜形态。结果生物被膜半定量结果:AMB组与空白组比较,P>0.05;黄芩素组低于AMB组和空白组,P均<0.05;黄芩素+AMB组低于黄芩素组,P<0.05。荧光显微镜下空白组和AMB组可见菌丝密集交叉缠绕,胞外基质丰富;黄芩素组菌丝仍密集交叉在一起,但菌丝细长、光滑,无明显胞外基质;黄芩素+AMB组菌丝明显减少,无明显胞外基质。结论黄芩素可以破坏烟曲霉生物被膜胞外基质。黄芩素与AMB联合应用可增加AMB对烟曲霉菌丝的渗透作用,提高其杀菌效果。     

生物被膜肺炎克雷伯菌超广谱β-内酰胺酶的检测

目的探讨生物被膜菌的耐药机制,为临床合理应用抗生素提供理论依据。方法对2004年4月至2005年11月中国医科大学附属第二医院应用改进的平板培养法建立的肺炎克雷伯菌生物被膜模型,用银染法和扫描电镜观察鉴定。以亚胺培南为诱导剂诱导生物被膜菌超广谱β-内酰胺酶的产生。采用标准纸片扩散确证法检测超广谱β-内酰胺酶,等电聚焦电泳测β-内酰胺酶的等电点。结果浮游肺炎克雷伯菌(A组)超广谱β-内酰胺酶的检出率为20.0%(8/40);生物被膜肺炎克雷伯菌(B组)超广谱β-内酰胺酶的检出率为42.5%(17/40);亚胺培南诱导生物被膜肺炎克雷伯菌(C组)超广谱β-内酰胺酶的检出率为65.0%(26/40)。对A组和B组的检出率,B组和C组的检出率进行χ2检验,结果差异均有显著性(P均<0.05)。结论生物被膜的形成和产生超广谱β-内酰胺酶的协同作用是肺炎克雷伯菌耐药的主要原因之一。     

生物被膜肺炎克雷伯菌超广谱β-内酰胺酶的检测

目的探讨生物被膜菌的耐药机制，为临床合理应用抗生素提供理论依据。方法对2004年4月至2005年11月中国医科大学附属第二医院应用改进的平板培养法建立的肺炎克雷伯菌生物被膜模型，用银染法和扫描电镜观察鉴定。以亚胺培南为诱导剂诱导生物被膜菌超广谱β-内酰胺酶的产生。采用标准纸片扩散确证法检测超广谱β-内酰胺酶，等电聚焦电泳测β-内酰胺酶的等电点。结果浮游肺炎克雷伯菌（A组）超广谱β-内酰胺酶的检出率为20．0％（8／40）；生物被膜肺炎克雷伯菌（B组）超广谱β-内酰胺酶的检出率为42．5％（17／40）；亚胺培南诱导生物被膜肺炎克雷伯菌（C组）超广谱β-内酰胺酶的检出率为65．0％（26／40）。对A组和B组的检出率，B组和C组的检出率进行x^2检验，结果差异均有显著性（P均〈0．05）。结论生物被膜的形成和产生超广谱β-内酰胺酶的协同作用是肺炎克雷伯菌耐药的主要原因之一。     

老年耐碳青霉烯肺炎克雷伯菌耐药机制及院内高毒力荚膜基因型分布特点

目的探讨老年耐碳青霉烯肺炎克雷伯菌感染的耐药机制,分析承德市中心医院高毒力荚膜基因型的分布特点。方法收集2016年1月至2017年3月间从承德市中心医院收治的老年患者中分离出的耐碳青霉烯肺炎克雷伯菌18株,鉴定菌株和药敏试验;采用改良Hodge试验、EDTA协同试验、Carba NP试验初筛碳青霉烯酶,进一步检测菌株毒力情况,PCR检测耐药基因、荚膜血清型和毒力基因。结果碳青霉烯酶检出Kpc基因6株(33.33%),Ndm基因7株(38.89%);超广谱β-内酰胺酶中Shv检出15株(83.33%),明显高于Ctx-M基因10株(55.56%)、Tem基因7株(38.89%)(P<0.01);AmpC酶中检出DHA基因2株(11.11%)。膜孔蛋白基因检测显示,Ompk36编码基因缺失率明显高于Ompk35(P<0.05);且当Ompk35基因缺失时Ompk36也缺失。荚膜分型显示,K1型4株,K57型2株,未检出K2、5、20及54,未分型12株;rmpA阳性率明显高于Acrobactin(P<0.05);4株K1型肺炎克雷伯菌均携带rmpA基因,其中1株同时携带Acrobactin基因;2株K57型肺炎克雷伯菌均携带rmpA基因;18株耐碳青霉烯肺炎克雷伯菌均携带FimH-1基因。结论老年耐碳青霉烯肺炎克雷伯菌感染的主要耐药机制为携带Kpc和Ndm基因以及超广谱β-内酰胺酶合并膜蛋白缺失;该院Kpc基因荚膜血清型菌株分离率较高,应加以重视。     

医源与动物源肺炎克雷伯菌耐药性和分子特性研究

目的了解不同宿主来源的肺炎克雷伯菌耐药性和分子特点,探讨其在人与动物间传播的可能性。方法收集2013年3月至2014年12月肺炎克雷伯菌98株(包含动物源67株、医源31株),通过K-B纸片扩散法和肉汤稀释法测定对15种抗菌药物的敏感性;拉丝试验测定产粘液表型;PCR扩增2个毒力基因和7个耐药基因;多位点序列(MLST)分析分子型。结果医源菌株耐药率显著高于动物源菌株,在动物源菌株中,鸡源和猪源菌株耐药率高于兔源和犬源菌株;除犬源菌株外均表现多重耐药,医源菌株多重耐药率最高(74.19%)。98株肺炎克雷伯菌有18个ST型,鸡源菌株主要流行ST37、猪源菌株为ST258、兔源菌株为ST60、犬源菌株为ST11,医源菌株为ST11。ST11为医源、犬源、猪源菌株共有,ST235为医源和鸡源菌株共有,ST258为医源和猪源菌株共有。高粘液菌株主要为ST11、ST235、ST258,且在这些分子型中检测到rmpA、magA基因。医源菌株blaKPC的检出率最高(54.84%),犬源和兔源菌株未检出BlaKPC基因。超广谱β-内酰胺酶基因在医源菌株中检出率高于动物源菌株,qnrA和qnrB基因在鸡源菌株中检出率高于医源菌株。ST11、ST258、ST235携带的多种耐药基因最高。结论不同宿主来源的肺炎克雷伯菌耐药表型、粘液表型及分子特性不同,但ST11、ST235、ST258为人源和动物源肺炎克雷伯菌共有的分子型。     

左氧氟沙星联合阿米卡星对肺炎克雷伯菌耐药突变选择窗的研究

目的探讨左氧氟沙星联合阿米卡星对肺炎克雷伯菌突变选择窗(MSW)的影响。方法琼脂倍比稀释法测定左氧氟沙星及其与阿米卡星联合对30株肺炎克雷伯菌的防突变浓度(MPC)和最低抑菌浓度(MIC),计算并比较左氧氟沙星单独及其与阿米卡星联合对肺炎克雷伯菌的选择指数(SI)。结果与阿米卡星联合,使左氧氟沙星对肺炎克雷伯菌的MPC范围由2～16 mg/l降至1～8 mg/L,MPC50由2 mg/L降至1 mg/L,MPC90由8 mg/L降至2 mg/L,P<0.01;左氧氟沙星单药及与联合阿米卡星对肺炎克雷伯菌的选择指数(SI)范围均在2～64,两组SI50均为16;SI90均为32,P>0.05;左氧氟沙星联合阿米卡星组较左氧氟沙星组SI降低的菌株有15株,无变化的有11株,增高的为4株。结论联合阿米卡星可降低左氧氟沙星对肺炎克雷伯菌的MPC,主要使左氧氟沙星对肺炎克雷伯菌的MSW变窄。     

老年呼吸道感染肺炎克雷伯菌耐药监测及产ESBLs基因型分析

目的分析老年患者呼吸道感染肺炎克雷伯菌的耐药性及产超广谱β-内酰胺酶(ESBLs)的基因型分布。方法对496份呼吸道感染的老年患者痰液标本进行培养,分离出的肺炎克雷伯菌用K-B法进行药敏分析,筛选产ESBLs菌株,并用PCR方法鉴定基因亚型。结果分离培养出肺炎克雷伯菌45株,占所有病原菌的11.9%。肺炎克雷伯菌对氨苄西林、氨苄西林/舒巴坦及复方新诺明耐药率高,达60%以上,而对亚胺培南、呋喃妥因及阿米卡星等的敏感性都很高。有31.1%的肺炎克雷伯菌株被鉴定出产ESBLs,且ESBLs基因型多以CTX-M-14、TEM和SHV为主,且92.9%的菌株存在2种及以上的基因型。结论该地区老年患者呼吸道感染肺炎克雷伯菌的耐药状况控制较好,但产ESBLs菌株携带多种耐药基因现象严重,需引起临床的高度重视。     

Effect of sodium hypochlorite on biofilm of Klebsiella pneumoniae with different drug resistance

BackgroundBiofilm formation is a major factor in the resistance mechanism of Klebsiella pneumoniae. This study aimed to evaluate the effects of sodium hypochlorite on the biofilm of K. pneumoniae with different drug resistance.MethodsWe collected 3 different types of K. pneumoniae respectively. The growth trend of biofilms of different drug-resistant K. pneumoniae was quantified by measuring the OD₅₉₀ for 7 consecutive days using crystal violet staining. Scanning confocal fluorescence microscopy was used to observe biofilm morphology.ResultsAfter adding sodium hypochlorite, there were significant differences between the OD₅₉₀ value of the 200, 500, and 1,000 µg/mL groups and the positive control group (all P < .05) on the fifth day. Concentrations of 2,000 and 5,000 µg/mL sodium hypochlorite were added after the biofilm had matured. In the 5,000 µg/mL sodium hypochlorite group, the OD₅₉₀ of K. pneumoniae biofilm in the 3 groups decreased significantly compared with the blank control group (all P < .05).ConclusionsSodium hypochlorite inhibited and cleared the biofilm of K. pneumoniae with different drug resistance, and the effect was enhanced with the increase of concentration in the range of bacteriostatic and bactericidal concentration.     

AWARE Ceftaroline Surveillance Program (2008-2010): Trends in Resistance Patterns Among Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States

Ceftaroline fosamil, the prodrug form of the active metabolite ceftaroline, is a new broad-spectrum parenteral cephalosporin with antibacterial activity against the prevalent respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Bacterial resistance surveillance (5330 isolates) was conducted in the United States between 2008 and 2010 to assess the in vitro activity of ceftaroline and comparator antibacterial agents against invasive respiratory isolates of S. pneumoniae (3329 isolates), H. influenzae (1545 isolates), and M. catarrhalis (456 isolates). All organisms were cultured from patient infections in 71 US hospital laboratories and were submitted to a central reference monitor for broth microdilution testing by Clinical and Laboratory Standards Institute reference methods. Against S. pneumoniae, ceftaroline inhibited 98.7% of strains at the susceptible breakpoint of ≤0.25?μg/mL (50% minimum inhibitory concentration [MIC(50)], 0.01?μg/mL; 90% MIC [MIC(90)], 0.12?μg/mL) and was 16-fold more active than ceftriaxone (MIC(90), 2?μg/mL). Among 70 ceftriaxone-resistant pneumococcal isolates, all were inhibited by ≤0.5?μg/mL of ceftaroline. Haemophilus influenzae (MIC(50), ≤0.008?μg/mL; MIC(90), 0.015?μg/mL) and M. catarrhalis (MIC(50), 0.06?μg/mL; MIC(90), 0.12?μg/mL) were very susceptible to ceftaroline regardless of β-lactamase production. Whereas the high-level of activity of ceftaroline was maintained against S. pneumoniae and H. influenzae from 2008 through 2010, increased rates of nonsusceptibility were observed for amoxicillin/clavulanate, erythromycin, and levofloxacin among S. pneumoniae and for trimethoprim/sulfamethoxazole and azithromycin among H. influenzae. In summary, ceftaroline resistance surveillance (Assessing Worldwide Antimicrobial Resistance Evaluation [AWARE] Program) in the United States (2008-2010) documented in vitro sustained potency and spectrum against Gram-positive and Gram-negative pathogens known to cause community-acquired bacterial pneumonia.     

In Vitro Activity of Ceftaroline Against Multidrug-Resistant Staphylococcus aureus and Streptococcus pneumoniae: A Review of Published Studies and the AWARE Surveillance Program (2008-2010)

Ceftaroline is a new broad-spectrum parenteral cephalosporin with antibacterial activity against the prevalent pathogens causing both acute bacterial skin and skin structure infections (ABSSSIs) and community-acquired bacterial pneumonia (CABP). The Assessing Worldwide Antimicrobial Resistance Evaluation Surveillance Program was conducted in the United States between 2008 and 2010 to assess the in vitro activity of ceftaroline and comparator antibacterial agents against ABSSSI and CABP pathogens. A total of 8469 Staphylococcus aureus isolates and 3593 Streptococcus pneumoniae isolates collected from 72 medical centers representing all US Census regions were submitted to a central reference laboratory (JMI Laboratories, North Liberty, IA) for broth microdilution testing by reference methods. The overall prevalence of methicillin resistance among S. aureus isolates was 52.6%, and although ceftaroline showed more potent activity against methicillin-susceptible S. aureus (minimum inhibitory concentration for 50% [MIC(50)] and 90% [MIC(90)] of organisms, both 0.25?μg/mL) than against methicillin-resistant S. aureus (MIC(50) and MIC(90), both 1?μg/mL), it showed good activity against all 8469 S. aureus isolates (MIC(50) and MIC(90), 0.5 and 1?μg/mL, respectively), with 8296 isolates (98.0%) testing susceptible at the US Food and Drug Administration (FDA) break point of ≤1?μg/mL and no isolates having MICs of >2?μg/mL. Against S. pneumoniae, ceftaroline inhibited 98.7% of tested isolates at the FDA susceptible break point of ≤0.25?μg/mL (MIC(50) and MIC(90), 0.015 and 0.12?μg/mL, respectively) and was 16-fold more active than ceftriaxone (MIC(90), 2?μg/mL). The prevalence of multidrug resistance among S. pneumoniae isolates was 30.1% overall and remained stable over each of the 3 monitored years. Ceftaroline demonstrated high activity (MIC(50) and MIC(90), 0.12 and 0.25?μg/mL, respectively) against multidrug-resistant S. pneumoniae, with only 44 of 1001 strains (4.4%) testing nonsusceptible and all 44 nonsusceptible strains having a ceftaroline MIC of only 0.5?μg/mL. Ceftriaxone resistance among S. pneumoniae was 2.1% (10.9% were nonsusceptible), with an intermediate susceptibility rate of 8.8%, resulting in an overall susceptibility rate of only 89.1%. Ceftaroline surveillance in the United States during 2008-2010 documented sustained potency and spectrum against multidrug-resistant S. aureus and multidrug-resistant S. pneumoniae known to cause ABSSSI and CABP.     

Über die antibakterielle Wirkung subinhibitorischer Tetracyclin-Konzentrationen

Zusammenfassung Bei Versuchen mit Tetracyclin stellten wir bei E. coli, Staphyloccus aureus, Klebsiella pneumoniae und Pseudomonas aeruginosa fest, daß Konzentrationen, die niedriger als die minimale Hemmkonzentration sind, zu einer partiellen Wachstumshemmung führen. Bei E. coli verursachten Konzentrationen zwischen 1/8 und 1/128 der minimalen Hemmkonzentrationen noch eine deutliche Partialhemmung. Bei Klebsiella pneumoniae lagen die minimale partielle Hemmkonzentration (MPHK) zwischen 1/64 und 1/512 bei Staph. aureus zwischen 1/16 und 1/32 und bei Pseudomonas aeruginosa zwischen 1/8 und 1/64 der minimalen Hemmkonzentration.Partialkativitäten von Antibiotika sollten in Zukunft stärker berücksichtigt werden.

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On the antibacterial effect of subinhibitory concentrations of tetracycline

Summary Trials with tetracycline of E. coli, Staphylococcus aureus, Klebsiella pneumonia and Pseudomenas aeruginosa established that concentrations lower that the minimal inhibitory concentrations (MIC) lead to a partial inhibition of growth. Concentrations between 1/8 and 1/128 of the MIC caused a distinct partial inhibition with E. coli. The partial MIC with Klebsiella pneumoniae was between 1/64 and 1/512, with Staph. aureus between 1/16 and 1/32 and with Pseudomonas aeruginosa between 1/8 and 1/64 of the MIC. The activity of antibiotics below the MIC should be given more consideration in the future.

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Die Testsubstanz wurde von Firma Farbwerke Hoechst zur Verfügung gestellt.     

汉防己甲素对氟康唑抗白念珠菌生物膜增效活性的初步研究

目的探讨汉防己甲素（tetrandrine,TET）对氟康唑（fluconazole,FLC）抗白念珠菌生物膜是否有增效活性。方法构建白念珠菌生物膜,参照微量稀释法,测定FLC单独及其联合TET对生物膜不同时期的最小抑菌浓度（minimum in-hibitory concentration,MIC）;生物膜重新悬浮后,测定FLC单独及其联合TET对不同浓度菌液的MIC。结果 FLC单独及其联合TET对白念珠菌生物膜最初期（0h）的MIC50值范围分别为0.25～64μg/mL和0.125～16μg/mL（P=0.002）;早期（4h）的MIC50值范围分别为8～256μg/mL和1～64μg/mL（P=0.000）;中期（24h）、成熟期（48h）的MIC50值均〉1024μg/mL。生物膜重新悬浮后,FLC单独及其联合TET对低浓度菌液（终浓度为1×103 CFU/mL）的MIC值范围分别为0.25～64μg/mL和0.125～16μg/mL（P=0.003）,高浓度菌液（终浓度为1×106 CFU/mL）的MIC值均〉64μg/mL。结论汉防己甲素在体外对氟康唑抗白念珠菌生物膜最初期（0h）、早期（4h）有增效活性,对中期（24h）、成熟期（48h）无增效活性;汉防己甲素对氟康唑抗白念珠菌生物膜重新悬浮后的低浓度菌液（终浓度为1×103 CFU/mL）有增效活性,高浓度菌液（终浓度为1×106 CFU/mL）无增效活性。     

Antimicrobial activity of Hibiscus sabdariffa extract against uropathogenic strains isolated from recurrent urinary tract infections

ObjectiveTo report the antimicrobial effect and biofilm forming capacity of the uropathogenic strains that have been isolated from recurrent urinary tract infections (UTIs) in the presence of Hibiscus sabdariffa (H. sabdariffa) extract.MethodsSix Escherichia coli and two Klebsiella pneumoniae isolates were collected from patients with recurrent UTIs. The susceptibility of bacterial isolates to H. sabdariffa extracts were tested by determining their minimum inhibitory concentrations (MICs), and minimum bactericidal concentration (MBC) by using the broth microdilution method in accordance to Clinical and Laboratory Standards Institute guidelines. Time-kill curves were plotted against the eight isolates based on the MIC results. The biofilm forming capacity of the isolates were evaluated using the microtiter plate assay. Detection of biofilms was done using the crystal violet staining method.ResultsVarious levels of the extracts MIC were observed against all the uropathogenic isolates. MIC values ranged from 0.5 to 4 mg/mL, and MBC values ranged from 8 to 64 mg/mL. Both the time-kill experiment and MBC-MIC ratio demonstrated that the extracts' effect was in general, bacteriostatic. The biofilm capacity inhibition assay results showed that extracts inhibited biofilm production of all the isolates. The level of biofilm inhibition however, had varied among the bacterial strains and ranged from 8%–60% reduction in optical density.ConclusionsThe results of the study support the effective potential of H. sabdariffa extract to prevent recurrent UTIs and to emphasize the significance of the plant extract, in order to approach it as a potential antimicrobial agent.     

黄连解毒汤对体外白念珠菌生物膜形成的影响

目的观察黄连解毒汤体外对白念珠菌生物膜形成的影响。方法采用结晶紫染色法和MTT法评价白念珠菌生物膜的体外生长动力学,微量稀释法检测黄连解毒汤对白念珠菌悬浮菌及其生物膜的抑制作用以及药物包被对白念珠菌生物膜形成作用。结果生物膜内白念珠菌数量随培养时间延长而增加。黄连解毒汤对白念珠菌悬浮菌的最低抑菌浓度50%(MIC50)为3.125mg/ml,对生物膜的SMIC50与SMIC80分别是3.125和6.25mg/ml。药物包被浓度在1.56mg/ml以上时对其生物膜形成的抑制作用有显著性。结论黄连解毒汤对体外白念珠菌生物膜具有明显的抑制作用。     

Quantitative measurement of airway dimensions using ultra-high resolution computed tomography

Background

Quantitative measurement of airway dimensions using computed tomography (CT) is performed in relatively larger airways due to the limited resolution of CT scans. Nevertheless, the small airway is an important pathological lesion in lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Ultra-high resolution scanning may resolve the smaller airway, but its accuracy and limitations are unclear.

Synthesis and Physicochemical Characterization of Novel Dicyclopropyl-Thiazole Compounds as Nontoxic and Promising Antifungals

There is a need to search for new antifungals, especially for the treatment of the invasive Candida infections, caused mainly by C. albicans. These infections are steadily increasing at an alarming rate, mostly among immunocompromised patients. The newly synthesized compounds (3a–3k) were characterized by physicochemical parameters and investigated for antimicrobial activity using the microdilution broth method to estimate minimal inhibitory concentration (MIC). Additionally, their antibiofilm activity and mode of action together with the effect on the membrane permeability in C. albicans were investigated. Biofilm biomass and its metabolic activity were quantitatively measured using crystal violet (CV) staining and tetrazolium salt (XTT) reduction assay. The cytotoxic effect on normal human lung fibroblasts and haemolytic effect were also evaluated. The results showed differential activity of the compounds against yeasts (MIC = 0.24–500 µg/mL) and bacteria (MIC = 125–1000 µg/mL). Most compounds possessed strong antifungal activity (MIC = 0.24–7.81 µg/mL). The compounds 3b, 3c and 3e, showed no inhibitory (at 1/2 × MIC) and eradication (at 8 × MIC) effect on C. albicans biofilm. Only slight decrease in the biofilm metabolic activity was observed for compound 3b. Moreover, the studied compounds increased the permeability of the membrane/cell wall of C. albicans and their mode of action may be related to action within the fungal cell wall structure and/or within the cell membrane. It is worth noting that the compounds had no cytotoxicity effect on pulmonary fibroblasts and erythrocytes at concentrations showing anticandidal activity. The present studies in vitro confirm that these derivatives appear to be a very promising group of antifungals for further preclinical studies.     

金黄色葡萄球菌致新西兰兔脓胸生物被膜模型的建立

目的：建立金黄色葡萄球菌感染的新西兰兔脓胸模型，观察其胸腔内是否有生物被膜形成。方法：选取24只健康雄性新西兰兔按随机数字表法分为实验组和对照组，各12只。通过胸腔穿刺术于右侧第六肋间隙将导管置入胸腔，实验组注射剂量为2 mL/kg的10⁸ CFU/mL金黄色葡萄球菌，对照组使用相同剂量的Luria-Bertani (LB)肉汤。建模后持续饲养并于第4天收集胸腔留置导管进行活菌计数和结晶紫染色。收集所有脓性絮状物的匀浆液和洗涤液用于菌落计数。切取壁层胸膜组织进行苏木精-伊红(HE)染色，观察胸膜病理改变情况；肽核酸荧光原位杂交(PNA-FISH)用于观察脓性絮状物中的生物被膜形成。结果：与对照组比较，实验组患侧胸腔有脓性絮状物形成和胸膜粘连。实验组导管菌落计数显著大于对照组(P<0.01),结晶紫染色OD值显著高于对照组(P<0.05)。通过计算匀浆液和洗涤液的CFU,验证了实验组胸腔内积聚了大量金黄色葡萄球菌。HE染色结果显示，实验组胸膜明显增厚，并伴随有大量炎症细胞浸润。PNA-FISH结果证实实验组兔子胸腔脓性絮状物中有生物被膜形成。结论：金黄色...