大环内酯类抗菌药对流感嗜血杆菌生物被膜的影响
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摘要
细菌生物被膜(bacteria biofilm BBF)可减弱细菌对抗菌药的敏感性,降低膜内药物的有效浓度,导致细菌不能彻底清除,疾病反复发作。慢性阻塞性肺疾病(chronic obstructive pulmonary diseases COPD)是临床常见的呼吸道疾病,居全球死亡原因的第4位。慢性阻塞性肺疾病急性发作(Acute ExplosionChronic Obstructive Pulmonary Diseases AECOPD)感染的特点是慢性过程急性反复发作,与BBF相关感染特点极其相似。流感嗜血杆菌是是导致AECOPD的主要致病菌之一。研究证实流感嗜血杆菌可在体外建立生物被膜,并逃逸抗菌药及免疫系统的攻击,提示流感嗜血杆菌BBF与AECOPD等慢性疾病的病程进展可能相关。COPD患者行机械通气呼吸机相关肺炎(ventilatorassociated pneumonia VAP)的发病率和死亡率均较高。气管导管生物被膜感染是导致VAP的原因之一。
目的:本实验通过建立流感嗜血杆菌体外和慢性支气管炎大鼠体内及气管导管生物被膜模型,并给予不同浓度大环内酯类抗菌药(红霉素、罗红霉素、阿奇霉素)干预,探讨大环内酯类抗菌药对流感嗜血杆菌生物被膜的影响。
方法:通过结晶紫染色及扫描电镜鉴定体外建立流感嗜血杆菌生物被膜;通过结晶紫染色评价不同浓度大环内酯类抗菌药物对流感嗜血杆菌早期生物被膜形成的影响及对成熟生物被膜的破坏作用,以筛选出抑制作用好的药物;通过扫描电镜观察药物对生物被膜基本结构的破坏;通过菌落计数观察药物对生物被膜内细菌的抑制作用。通过熏烟结合脂多糖气道内滴入法建立慢性支气管炎大鼠模型;通过琼脂珠包被菌体气道滴入法建立慢性支气管炎大鼠流感嗜血杆菌急性感染模型;通过肺泡灌洗液、肺组织匀浆菌落计数及扫描电镜、病理切片观察慢支急性发作大鼠肺内生物被膜的形成;通过肺泡灌洗液、肺组织匀浆菌落计数和大鼠肺泡灌洗液及血清中TNF-α、IL-6、IL-8水平的变化,评价阿奇霉素灌胃治疗流感嗜血杆菌感染慢支大鼠的作用。并评价各炎性因子在慢支急性发作中的地位。采用慢性支气管炎大鼠气管置管,给予细菌气道滴入流感嗜血杆菌造成气管插管感染模型,并在扫描电镜下观察气管内导管生物被膜形成情况。通过气管导管菌落计数评价阿奇霉素在治疗气管导管生物被膜的作用。
结果:通过结晶紫染色及扫描电镜证实体外成功建立流感嗜血杆菌生物被膜;通过结晶紫染色观察到,流感嗜血杆菌在亚MIC浓度仍可形成生物被膜,大环内酯类抗茵药对生物被膜有一定抑制作用。其中在对早期生物被膜抑制作用的观察中,阿奇霉素组随药物浓度的增高形成的生物被膜的能力减弱,但同样为大环内酯类抗菌药物的罗红霉素和红霉素组,在1/8MIC浓度时形成生物被膜的能力较其它浓度为高(P＜0.05),甚至高于无药对照组;在对成熟生物被膜破坏作用的结果显示,阿奇霉素组随药物浓度的升高对生物被膜的破坏力越强,并且,亚MIC的阿奇霉素对成熟生物被膜也显示出了一定的破坏作用。通过扫描电镜及菌落计数进一步观察阿奇霉素对生物被膜影响的结果显示阿奇霉素可破坏生物被膜的基本结构,使被膜表面粗糙、结构疏松,并且在1/8MIC-8MIC浓度可不同程度的抑制生物被膜内细菌数,但是在8MIC时仍未能彻底清除膜内细菌。慢性支气管炎模型组动物的气道组织病理学可见支气管黏膜上皮纤毛倒伏、脱落、管腔分泌物增多、炎细泡浸润、杯状细胞增生、平滑肌断裂。对照组气道黏膜上皮完整,纤毛无黏连、脱落,未见炎细胞浸润。对照组和慢支组大鼠肺泡灌洗液和肺组织匀浆细菌数在第一天时接种数均为10~7以上,病理显示对照组肺泡腔、气管旁及肺问质均出现大量炎细胞浸润,以中性粒细胞浸润为主,肺组织呈实变;慢支组肺泡腔及肺间质大量炎细胞浸润,炎细胞在淋巴细胞浸润的基础上出现中性粒细胞,且肺泡腔渗出明显,部分呈实变;提示急性感染模型成功建立。慢支组肺组织匀浆中细菌数显示在2周时最低,至一月时仍保持在10~2,且略有升高趋势。扫描电镜观察慢支感染大鼠肺组织内可见一外被膜样结构物质,内呈颗粒改变,结合光镜下可见肉芽肿内异物巨细胞包绕下被染成黑色颗粒状的菌体。阿奇霉素作用于慢支急性发作大鼠结果显示,肺泡灌洗液菌落计数中,给药组与慢支组相比细菌清除时间明显提前,在肺组织匀浆中慢支组及给药组一月时细菌仍未能彻底清除,但从细菌计数来看给药组较慢支组明显减少;病理显示给予阿奇霉素治疗后与未用药物干预组同期相比炎细胞浸润明显减少,肺泡腔渗出吸收;三种炎性因子数值给药组均较感染组明显降低。当肺泡灌洗液中细菌数高时三种细胞炎性因子水平均较高,并随细菌数减少,数值不同程度下降,且当肺组织内有细菌定植时,炎性因子水平高于对照组,低于感染组。给药组IL-6及IL-8肺泡灌洗液中数值在一周左右时低于对照组。扫描电镜可见导管上生长的生物被膜表面凹凸不平,并见大量胞外基质包被下的细长菌体,证实流感嗜血杆菌可在气管内导管形成生物被膜。阿奇霉素作用后,气管导管生物被膜内细菌数与未用药相比有所下降,但一月后与未用药相比无明显差异。
结论:流感嗜血杆菌可在体外形成生物被膜。流感嗜血杆菌在大环内酯类抗菌药(阿奇霉素、罗红霉素、红霉素)亚MIC浓度时可形成生物被膜。大环内酯类抗菌药对生物被膜有一定破坏作用,其中阿奇霉素作用最强。高浓度及亚MIC浓度阿奇霉素均可影响生物被膜黏附性、破坏生物被膜基本结构,并可减少膜内活菌数,但不能完全清除膜内细菌。本实验成功建立慢性支气管炎及慢性支气管炎流感嗜血杆菌急性感染大鼠模型并在慢性支气管炎大鼠体内可见生物被膜样物质。阿奇霉素对慢支流感嗜血杆菌生物被膜感染大鼠急性期及生物被膜内细菌均有较好治疗作用。细胞炎性因子可作为评价感染程度的指标。阿奇霉素有抑制大鼠IL-6及IL-8的作用。流感嗜血杆菌可在气道导管内形成生物被膜。阿奇霉素对流感嗜血杆菌气道内导管生物被膜有一定抑制作用。
Bacteria biofilm(BBF) can attenuates bacteria sensitivity to antibiotics, reduce the antibiotics concentration in biofilm,and leads to incomplete elimination of bacteria and disease recurrence.Chronic obstructive pulmonary disease(COPD) is a respiratory tract disease commonly seen in clinics,which is the fourth cause of death on the planet.Infectious characteristics of acute exacerbations of COPD are chronicity of disease and acute attacks repeatedly, which is similar with biofilm-associated infections.Nontypeable Haemophilus influenzae is the major pathogenic bacteria of many chronic recurrent diseases, including acute Explosion of chronic obstructive pulmonary diseases(AECOPD). It was reported that Haemophilus influenza can form BBF in vitro and escape the attack of antibiotics and immune system,which suggested that Haemophilus influenza BBF might be associated with the progress of AECOPD.Ventilation associated pneumonia(VAP) is commonly seen during mechanical ventilation, which can result in high morbidity and mortality,especially in patients with chronic obstructive pulmonary diseases.Biofilm formed on endotracheal tube is one of important causes of VAP.
Objective:To determine the activity of the macrolides in the treatment of infection associated with Nontypeable Haemophilus influenzae Biofilm Formation in vivo,vitro and on endotracheal tubes.
Methods:Formation of bacterial biofilm was examined by crystal violet assay and scanning electron microscope.Alterations of biofilms were measured under varying concentrations of macrolides In vitro.We evaluate the destruction of different concentrations azithromycin on Haemophilus Influenzae biofilms through crystal violet assay and scanning electron microscope,viable cells counting in biofilms was also carried out.Rat models of chronic bronchitis were established by instillation of LPS and smoking,which were infected by Haemophilus influenzae coated by agar beads to build the rat models of acute exacerbation of chronic bronchitis.Formation of biofilms was determined by viable cells count in BALF and lung tissue homogenate,and pathology under SEM and light microscope.Levels of TNF-α、IL-6、IL-8 in serum and BALF and quantity of bacteria in BALF and homogenate were measured to evaluate the effects of azithromycin administered orally on model rats infections by Haemophilus influenzae,and to judge the role of inflammatory factors in pathophysiology of AECOPD.Chronic bronchitis rats were intubated with a silicone tube,and then infected by bacteria to establish the animal models of endotracheal tube infections.Formation of biofilms was detected by SEM.Viable cells counting was carried out to evaluate the effect of azithromycin orally on biofilms on endotracheal tubes.
Results:Through crystal violet assay,Biofilm synthesis was observed at subMIC and stronger in Roxithromycin and Erythromycin at 1/8 MIC,inhibited by Azithromycin at higher concentrations.Disruption of mature biofilms could be achieved at relatively higher concentration,Azithromycin displayed more powerful activity.Optical density of biofilms and viable cell counting were significantly decreased at the concentration of 8 folds of MIC for azithromycin, and biofilm structure was destroyed by azithromycin at concentration of 10 folds of MIC.at subMIC,azithromycin could damage the biofilm formation of Nontypeable Haemophilus influenzae and reduce the viable cell counting. Pathology of respiratory tract tissue of rats with chronic bronchitis showed lodging of cilia,exuviation,increase of secretion in lumens,infiltration of inflammatory cells,proliferation of goblet cells,rupture of smooth muscles. Comparatively,intactness of mucosal epithelium,smooth muscles were shown in control group.Quantity of bacteria in BALF and homogenate on day 1 after inoculation was higher than 10~7 both in control and chronic bronchitis groups.A lot of inflammatory cells,infiltrated into alveolus,parabronchial area and interstitium,accompanied with lung tissue consolidation and more exudations in chronic bronchitis rats.Viable cells count in homogenate of chronic bronchitis rats dropped to the lowest level after 2 weeks,and maintained at 10~2 after 1 month with an increasing trend.Biofilm-like structure was found in infected chronic bronchitis rats lung tissue under SEM,which entrapped the bodies of bacteria. Bacteria in BALF of infected chronic bronchitis rats were eliminated more quickly after azithromycin administration.Bacteria in homogenate could be detected even after 1 month with or without drug therapy,but,viable cells count was significantly lower in azithromycin group.Pathological results also showcased that infiltration of inflammatory cells and exudations in alveolus were conspicuously alleviated after azithromycin therapy.Levels of 3 inflammatory factors were markedly reduced in azithromycin group.Inflammatory factors held on to a relatively higher level when more bacteria survived in BALF,and decreased with the falling of viable cells count.When bacteria colonized in lung tissue,levels of inflammatory factors were higher than that in control group,but lower than that in infections group.Levels of IL-6 and IL-8 in BALF were lower after 1 week in drug group than that in control group.Uneven biofilms were formed on the surface of endotracheal tubes under SEM,and slim bodied of bacteria enclosed by a lot of extracellular matrix.Viable cells counting was reduced by azithromycin compared with that without drug,but there was no difference after 1 month.
Conclusions:Haemophilus Influenzae is capable to form biofilm in vitro,in vivo of chronic bronchitis rats and on endotracheal tubes,Haemophilus Influenzae is capable to form biofilm in subconcentration of AZI,ROX and ERY. Sufficient dosage might control early formation of biofilms.Azithromycin exerts better effects on breakdown of biofilm than other macrolides.Azithromycin was able to interfere with adhesion,damage the structure of biofilm,and reduce viable cells counting at high concentrations.Rat models of chronic bronchitis and acute infection of chronic bronchitis by Haemophilus influenzae were established. Azithromycin exerts excellent therapeutic effects on acute exacerbations of chronic bronchitis infected by Haemophilus influenzae,and eradication of bacteria in biofilms.Inflammatory factors can be regarded as measurement of evaluating the degree of infections.Azithromycin can reduce the level of IL-6 and IL-8. Azithromycin can exert inhibitory effect on Haemophilus influenzae biofilms formed on endotracheal tubes.
目的:本实验通过建立流感嗜血杆菌体外和慢性支气管炎大鼠体内及气管导管生物被膜模型,并给予不同浓度大环内酯类抗菌药(红霉素、罗红霉素、阿奇霉素)干预,探讨大环内酯类抗菌药对流感嗜血杆菌生物被膜的影响。
方法:通过结晶紫染色及扫描电镜鉴定体外建立流感嗜血杆菌生物被膜;通过结晶紫染色评价不同浓度大环内酯类抗菌药物对流感嗜血杆菌早期生物被膜形成的影响及对成熟生物被膜的破坏作用,以筛选出抑制作用好的药物;通过扫描电镜观察药物对生物被膜基本结构的破坏;通过菌落计数观察药物对生物被膜内细菌的抑制作用。通过熏烟结合脂多糖气道内滴入法建立慢性支气管炎大鼠模型;通过琼脂珠包被菌体气道滴入法建立慢性支气管炎大鼠流感嗜血杆菌急性感染模型;通过肺泡灌洗液、肺组织匀浆菌落计数及扫描电镜、病理切片观察慢支急性发作大鼠肺内生物被膜的形成;通过肺泡灌洗液、肺组织匀浆菌落计数和大鼠肺泡灌洗液及血清中TNF-α、IL-6、IL-8水平的变化,评价阿奇霉素灌胃治疗流感嗜血杆菌感染慢支大鼠的作用。并评价各炎性因子在慢支急性发作中的地位。采用慢性支气管炎大鼠气管置管,给予细菌气道滴入流感嗜血杆菌造成气管插管感染模型,并在扫描电镜下观察气管内导管生物被膜形成情况。通过气管导管菌落计数评价阿奇霉素在治疗气管导管生物被膜的作用。
结果:通过结晶紫染色及扫描电镜证实体外成功建立流感嗜血杆菌生物被膜;通过结晶紫染色观察到,流感嗜血杆菌在亚MIC浓度仍可形成生物被膜,大环内酯类抗茵药对生物被膜有一定抑制作用。其中在对早期生物被膜抑制作用的观察中,阿奇霉素组随药物浓度的增高形成的生物被膜的能力减弱,但同样为大环内酯类抗菌药物的罗红霉素和红霉素组,在1/8MIC浓度时形成生物被膜的能力较其它浓度为高(P＜0.05),甚至高于无药对照组;在对成熟生物被膜破坏作用的结果显示,阿奇霉素组随药物浓度的升高对生物被膜的破坏力越强,并且,亚MIC的阿奇霉素对成熟生物被膜也显示出了一定的破坏作用。通过扫描电镜及菌落计数进一步观察阿奇霉素对生物被膜影响的结果显示阿奇霉素可破坏生物被膜的基本结构,使被膜表面粗糙、结构疏松,并且在1/8MIC-8MIC浓度可不同程度的抑制生物被膜内细菌数,但是在8MIC时仍未能彻底清除膜内细菌。慢性支气管炎模型组动物的气道组织病理学可见支气管黏膜上皮纤毛倒伏、脱落、管腔分泌物增多、炎细泡浸润、杯状细胞增生、平滑肌断裂。对照组气道黏膜上皮完整,纤毛无黏连、脱落,未见炎细胞浸润。对照组和慢支组大鼠肺泡灌洗液和肺组织匀浆细菌数在第一天时接种数均为10~7以上,病理显示对照组肺泡腔、气管旁及肺问质均出现大量炎细胞浸润,以中性粒细胞浸润为主,肺组织呈实变;慢支组肺泡腔及肺间质大量炎细胞浸润,炎细胞在淋巴细胞浸润的基础上出现中性粒细胞,且肺泡腔渗出明显,部分呈实变;提示急性感染模型成功建立。慢支组肺组织匀浆中细菌数显示在2周时最低,至一月时仍保持在10~2,且略有升高趋势。扫描电镜观察慢支感染大鼠肺组织内可见一外被膜样结构物质,内呈颗粒改变,结合光镜下可见肉芽肿内异物巨细胞包绕下被染成黑色颗粒状的菌体。阿奇霉素作用于慢支急性发作大鼠结果显示,肺泡灌洗液菌落计数中,给药组与慢支组相比细菌清除时间明显提前,在肺组织匀浆中慢支组及给药组一月时细菌仍未能彻底清除,但从细菌计数来看给药组较慢支组明显减少;病理显示给予阿奇霉素治疗后与未用药物干预组同期相比炎细胞浸润明显减少,肺泡腔渗出吸收;三种炎性因子数值给药组均较感染组明显降低。当肺泡灌洗液中细菌数高时三种细胞炎性因子水平均较高,并随细菌数减少,数值不同程度下降,且当肺组织内有细菌定植时,炎性因子水平高于对照组,低于感染组。给药组IL-6及IL-8肺泡灌洗液中数值在一周左右时低于对照组。扫描电镜可见导管上生长的生物被膜表面凹凸不平,并见大量胞外基质包被下的细长菌体,证实流感嗜血杆菌可在气管内导管形成生物被膜。阿奇霉素作用后,气管导管生物被膜内细菌数与未用药相比有所下降,但一月后与未用药相比无明显差异。
结论:流感嗜血杆菌可在体外形成生物被膜。流感嗜血杆菌在大环内酯类抗菌药(阿奇霉素、罗红霉素、红霉素)亚MIC浓度时可形成生物被膜。大环内酯类抗菌药对生物被膜有一定破坏作用,其中阿奇霉素作用最强。高浓度及亚MIC浓度阿奇霉素均可影响生物被膜黏附性、破坏生物被膜基本结构,并可减少膜内活菌数,但不能完全清除膜内细菌。本实验成功建立慢性支气管炎及慢性支气管炎流感嗜血杆菌急性感染大鼠模型并在慢性支气管炎大鼠体内可见生物被膜样物质。阿奇霉素对慢支流感嗜血杆菌生物被膜感染大鼠急性期及生物被膜内细菌均有较好治疗作用。细胞炎性因子可作为评价感染程度的指标。阿奇霉素有抑制大鼠IL-6及IL-8的作用。流感嗜血杆菌可在气道导管内形成生物被膜。阿奇霉素对流感嗜血杆菌气道内导管生物被膜有一定抑制作用。
Bacteria biofilm(BBF) can attenuates bacteria sensitivity to antibiotics, reduce the antibiotics concentration in biofilm,and leads to incomplete elimination of bacteria and disease recurrence.Chronic obstructive pulmonary disease(COPD) is a respiratory tract disease commonly seen in clinics,which is the fourth cause of death on the planet.Infectious characteristics of acute exacerbations of COPD are chronicity of disease and acute attacks repeatedly, which is similar with biofilm-associated infections.Nontypeable Haemophilus influenzae is the major pathogenic bacteria of many chronic recurrent diseases, including acute Explosion of chronic obstructive pulmonary diseases(AECOPD). It was reported that Haemophilus influenza can form BBF in vitro and escape the attack of antibiotics and immune system,which suggested that Haemophilus influenza BBF might be associated with the progress of AECOPD.Ventilation associated pneumonia(VAP) is commonly seen during mechanical ventilation, which can result in high morbidity and mortality,especially in patients with chronic obstructive pulmonary diseases.Biofilm formed on endotracheal tube is one of important causes of VAP.
Objective:To determine the activity of the macrolides in the treatment of infection associated with Nontypeable Haemophilus influenzae Biofilm Formation in vivo,vitro and on endotracheal tubes.
Methods:Formation of bacterial biofilm was examined by crystal violet assay and scanning electron microscope.Alterations of biofilms were measured under varying concentrations of macrolides In vitro.We evaluate the destruction of different concentrations azithromycin on Haemophilus Influenzae biofilms through crystal violet assay and scanning electron microscope,viable cells counting in biofilms was also carried out.Rat models of chronic bronchitis were established by instillation of LPS and smoking,which were infected by Haemophilus influenzae coated by agar beads to build the rat models of acute exacerbation of chronic bronchitis.Formation of biofilms was determined by viable cells count in BALF and lung tissue homogenate,and pathology under SEM and light microscope.Levels of TNF-α、IL-6、IL-8 in serum and BALF and quantity of bacteria in BALF and homogenate were measured to evaluate the effects of azithromycin administered orally on model rats infections by Haemophilus influenzae,and to judge the role of inflammatory factors in pathophysiology of AECOPD.Chronic bronchitis rats were intubated with a silicone tube,and then infected by bacteria to establish the animal models of endotracheal tube infections.Formation of biofilms was detected by SEM.Viable cells counting was carried out to evaluate the effect of azithromycin orally on biofilms on endotracheal tubes.
Results:Through crystal violet assay,Biofilm synthesis was observed at subMIC and stronger in Roxithromycin and Erythromycin at 1/8 MIC,inhibited by Azithromycin at higher concentrations.Disruption of mature biofilms could be achieved at relatively higher concentration,Azithromycin displayed more powerful activity.Optical density of biofilms and viable cell counting were significantly decreased at the concentration of 8 folds of MIC for azithromycin, and biofilm structure was destroyed by azithromycin at concentration of 10 folds of MIC.at subMIC,azithromycin could damage the biofilm formation of Nontypeable Haemophilus influenzae and reduce the viable cell counting. Pathology of respiratory tract tissue of rats with chronic bronchitis showed lodging of cilia,exuviation,increase of secretion in lumens,infiltration of inflammatory cells,proliferation of goblet cells,rupture of smooth muscles. Comparatively,intactness of mucosal epithelium,smooth muscles were shown in control group.Quantity of bacteria in BALF and homogenate on day 1 after inoculation was higher than 10~7 both in control and chronic bronchitis groups.A lot of inflammatory cells,infiltrated into alveolus,parabronchial area and interstitium,accompanied with lung tissue consolidation and more exudations in chronic bronchitis rats.Viable cells count in homogenate of chronic bronchitis rats dropped to the lowest level after 2 weeks,and maintained at 10~2 after 1 month with an increasing trend.Biofilm-like structure was found in infected chronic bronchitis rats lung tissue under SEM,which entrapped the bodies of bacteria. Bacteria in BALF of infected chronic bronchitis rats were eliminated more quickly after azithromycin administration.Bacteria in homogenate could be detected even after 1 month with or without drug therapy,but,viable cells count was significantly lower in azithromycin group.Pathological results also showcased that infiltration of inflammatory cells and exudations in alveolus were conspicuously alleviated after azithromycin therapy.Levels of 3 inflammatory factors were markedly reduced in azithromycin group.Inflammatory factors held on to a relatively higher level when more bacteria survived in BALF,and decreased with the falling of viable cells count.When bacteria colonized in lung tissue,levels of inflammatory factors were higher than that in control group,but lower than that in infections group.Levels of IL-6 and IL-8 in BALF were lower after 1 week in drug group than that in control group.Uneven biofilms were formed on the surface of endotracheal tubes under SEM,and slim bodied of bacteria enclosed by a lot of extracellular matrix.Viable cells counting was reduced by azithromycin compared with that without drug,but there was no difference after 1 month.
Conclusions:Haemophilus Influenzae is capable to form biofilm in vitro,in vivo of chronic bronchitis rats and on endotracheal tubes,Haemophilus Influenzae is capable to form biofilm in subconcentration of AZI,ROX and ERY. Sufficient dosage might control early formation of biofilms.Azithromycin exerts better effects on breakdown of biofilm than other macrolides.Azithromycin was able to interfere with adhesion,damage the structure of biofilm,and reduce viable cells counting at high concentrations.Rat models of chronic bronchitis and acute infection of chronic bronchitis by Haemophilus influenzae were established. Azithromycin exerts excellent therapeutic effects on acute exacerbations of chronic bronchitis infected by Haemophilus influenzae,and eradication of bacteria in biofilms.Inflammatory factors can be regarded as measurement of evaluating the degree of infections.Azithromycin can reduce the level of IL-6 and IL-8. Azithromycin can exert inhibitory effect on Haemophilus influenzae biofilms formed on endotracheal tubes.
引文
[1]Timothy D.Starner,Niu Zhang,GunHee Kim.Haemophilus influenzae Forms Biofilms on Airway Epithelia Implications in Cystic Fibrosis.American Journal of Respiratory and Critical Care Medicine.2006,(174):213-22
[2]Costerton,JW,G Geesey,and GK Cheng.How bacteria stick[J].Sci Am.1978,238:86-95.
[3]唐子圣,朱敏,刘正.抗菌剂作用后变形链球菌生物膜细胞活力观察.临床口腔医学杂志.2007,7(21):387-389
[4]小林宏行.细菌菌膜的基础与临床[J].中国临床药理学杂志,1999;15(4):299-307.
[5]Katateda,Rachel Comte,Jean-Claude Pechere et al.Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa,ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2001(6):1930-1933.
[6]张梅,王睿等.大环内酯类抗菌药物对加替沙星透过细菌生物被膜的影响.中华医院感染学杂志,2005,7(15):725-27
[7]Post JC.Direct evidence of bacterial biofilms in otitis media.Laryngoscope.2001,111(12):2083-2094.
[8]修清玉,方正,赖国祥等.改良流感嗜血杆菌培养基的实验研究与评价.中华医学检验杂志.1998,21(3):161-163.
[9]Murphy TF,Kirkham C.Biofilm formation by nontypeable Haemophilus influenzae:strain variability,outer membrane antigen expression and role of pili.BMC Microbiol.2002,(2):7.
[10]Clinical and Laboratory Standards Institute.Performance standards for antimicrobial susceptibility testing,seventeenth informational supplement.M100-S17.Wayne,PA:CLSI;2007.
[11]Tomoku I,Kaori T,Kazufiumi H,et al.The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro.Chemother,1996,42:186-191.
[12]Potera C.Forging a link between biofilm and disease [J].Science,1999,283:1873
[13]Sugita J,Yokoi N,Fullwood NJ,et al.The Detection of Bacterial biofilms in Punctal Plug Holes[J].Coenea.2001,20:362-365.
[14]Hall-Stoodley L,Hu FZ,Gieseke A.Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.JAMA.2006 Jul 12;296(2):202-11.
[15]Martin Kuehn,Martina Hausner,Hans-Joach in Bungartz,etal.Automated confocal laser scanning microscopy and semiautomated miage processing for analysis of biofilms[J].Appl Environ Microbiol 1998,64:4115-4127.
[16]冯丽萍.细菌生物膜[A].见:徐建国.分子医学细菌学[M].第1版.北京:科学出版,2000:173-178
[17]Sutherland I W.The biofilm matrix an immobilized but dynamic microbial environment[J].Trends Microbiol.2001,9:222-227
[18]Sethi S.Pathogenesis and treatment of acute exacerbations of chronic obstructive pulmonary disease.Seminars in Respiratory Mediators in the Critical Care Medicine.2005,26:192-201.
[19]Bayston R,Rodgers J.Production of extra-cellular slime by Staphylococcus epidermidis:during stationary phase of growth:its association with adherence to implantable devices.J Clin Pathol,1990,43:866-870.
[20]Christensen GD,Simpson WA,Bisno AL,et al.Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces.Infect Immun.1982,37:318-326
[21]Hlentzer M,Givskov M,Eber L.Quorum sensing in biofilms:Gossip in slime city[M].Washington DC:American Society for Microbiology Press,2004:118
[22]Davies DG,Parsek MR,Pearson JP,et al.The involvement of cell-to-cell signals in the development of a bacterial biofilm[J].Science.1998,280:295-301
[23]Shih Pei-Ching,Huang Ching -Tsan.Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance[J].J Antimicrob Chemother,2002,49:309-14
[24]Walters MC,Roe F,Bugnicourt A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginose biofilm to ciprofloxacin and tobramycin.Atimicrobial Agents and Chemo-therapy.2003,47(1):317-323.
[25]Thien-Fah CM.O' Toole GA.Mechanisms of biofilm resistance to antimicrobial agents.Trends in Microbiol.2001,9(1):34-39.
[26]Timothy D.Stamer,Joshua D.Shrout,Matthew R.Parsek,Peter C.Appelbaum,and GunHee Kim,Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation andDiminish Established Biofilms. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2008,1(52):137-145
[27]Hoffman LR,David A.D Argenio,Michae J.MacCoss.Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005, 436(7054):1171-1175.
[28]Tateda,K.,Y.Ishii,Y.Hirakata,T.Matsumoto,A.Ohno,and K.Yamaguchi.Profiles of outer membrane proteins and lipopolysaccharide of Pseudomonas aeruginosa grown in the presence of sub-MICs of macrolide antibiotics and their relation to enhanced serum sensitivity. J. Antimicrob.Chemother.1994.34:931-942.
[29]Gillis.R.J and B.H.Iglewski.Azithromycin retards Pseudomonas aeruginosa biofilm formation.J.Clin.Microbiol.2004,42:5842-5845.
[30]Timothy D,Starner Joshua D,Shrout,Matthew R.Parsek,et al.Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms.Antimicrobial Agents and Chemotherary.2008,1(52).137-145
[31]C.Water,B.L.Bassler.Quorum sensing:cell-to-cell communication in bacteria.Annu.Re v.Cell Dev.Biol.2005,(21):319-346
[32]Wlters M C,Roe F,Bugnicout A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin[J]·Antimicrob Agents Chemother.2003,47:317～323
[33]SouliM, and H.GIAMarellou.Effects of slime produced by clinical isolates of coagulase-negative staphylococcion activities of various antimicrobial agents[J].antimicrob Agents Chemother,1998 42:939~941
[34] Stewart PS, Costerton JW .Antibiotic resistance in biofilms[J].Lancet.2001,358:135-138.
[35]Costerton J W,Stewart P S.Battling biofilms[J].Sci.2001,285(1):74-81
[36]Wlters M C,Roe F,Bugnicout A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin[J].Antimicrob Agents Chemother.2003,47:317～32
[37]Karen D,Mcfeters G A,Stewart P S.Biofilm resistance to antimicrobial agents[J]-Microbiology.2000,146:547 ~ 549.
[38]Gordon R,Bachmann S,Patterson TF,et al.Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms[J].J Antimicrob Chemother.2002,49:973-980.
[39]Mah T,Pitts B,Pellock B,et al.A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance[J].Nature.2003,426:306-310.
[40]王霞,梁德荣,苗佳．华西医学．2003,18(1):146～1461
[41]C.Water,B.L.Bassler.Quorum sensing:cell-to-cell communication in bacteria.Annu.Re v.Cell Dev.Biol.2005,(21):319-346
[42]Mette E.Skindersoe,Morten Alhede,l Richard Phipps,et al,Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa,Antimicrobial Agents And Chemotherary.2008,(52):3648-3663
[43]Ute Romling and Dorit Amikam.Cyclic di-GMP as a second messenger.Current Opinion in Microbiology.2006,(9):218-228
[44]Balaban NQ,Merrin J,Chait R,et al.Bacterial persistence as a phenotypic switch[J].Science.2004,305(10):1622-25
[45]Baumann U,King M,App EM,et al.Long term azithromycin therapy in cystic fibrosis patients:a study on drug levels and sputum properties.Can Respir J.2004,11(2):151-155.
[46]Spoering AL,Lewis K.Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials[J].J Bacteriol.2001,183(23):6746-6751
[47]Wilms EB,Touw DJ,Heijerman HG.Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit,2006,28(2):219-25
[48]Olsen,K.M,G.San Pedro,L.P.Gann et al.Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses Antimicrob.Agents Chemother.1996,40:2582-2585
[49]Tamura A,Ara T,Imamira Y et al.The effects of antibiotics on in vitro biofilm model of periodontal disease.Eur J Med Res.2008,9:439-445
[1]Sethi S,Murphy TE Bacterial infection in chronic obstructive pulmonary disease in 2000:a State of the Art Review.Clin Microbiol Rew,2001:336-363.
[2]Murphy TF,Brauer AL,Schiffmacher AT,et al.Persistent colonazation by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004,170:266-272.
[3]Buck C.Bundschu J.Gallati H.et al.lnterleukin.6:A soncitive pa.rameter for the early diagnosis of neonatal bacterial infection[J].Pediatrics.1994,93:54-58.
[4]Cree RT,Warnell I,Staunton M,et al.Alveolar and plasma concentrations of interleukin-8 and vascular endothelial growth factor following oesophagectomy[J].Anaesthesia.2004,59(9):867-71.
[5]Katateda,Rachel Comte,Jean-Claude Pechere et al,Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa,ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2001,(6):1930-1933.
[6]李影林.临床微生物学及检验.人民卫生出版社,1995,673
[7]Ishlda Y.Experimental pneumonia with Pseudomonas aeruginosain immunosuppressed guinea pigs as a model for biofilm-associated infection.Kansen sho gaku Zasshi.1995,69(5):572-81
[8]Cosio M,Chezzo H,Hogg JC.et al.The relations between structural changes in small airways and pulmonary function tests.N Engl J Med.1978,298(23):1277-1281.
[9]Slater LN.A rat model nontypable Haemophilus of prolonged pulmonary infection due to influenzae.Am Rev Respir Dis.1990,142:1429-1435
[10]张永,程德云,王慧,等.慢性阻塞性肺疾病大鼠肺内白细胞介素—8和肿瘤坏死因子-α与气道炎症的关系研究.中国呼吸与危重监护杂志.2003,2(6):355—359.
[11]Murphy TF,Kirkham C.Biofilm formation by nontypeable Haemophilus influenzae:strain variability,outer membrane antigen expression and role of pili. BMC Microbiol.2002,(2):7
[12]Mannino DM.Chronic obstructive pulmonary disease:definition and epidemiology.Respir Care.2003,48:1185-1191
[13]Regional COPD Working Group.COPD prevalence in 12 Asia-Pacific countries and regions:projections based on the COPD prevalence estimation model.Respirology.2003,8:192-198
[14]Hoban DJ,Biedenbach DJ,Mutnick AH,et al.Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America:results of the SENTRY Antimicrobial Surveillance Study(2000)[J].Diagn Microbiol Infect Dis.2003,45(4):279-285.
[15]Hall-Stoodley L,Hu FZ,Gieseke A.Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.JAMA.200612(2):202-11.
[16]Andrew Churg,Manuel Cosio,and Joanne L.Wright.Mechanisms of cigarette smoke-induced COPD:insights from animal models.Am J Physiol Lung Cell Mol Physiol.2008,294:L612-L631
[17]XU Jianying,et al.Establishment and pathological study of models of chronic obstructive pulmonary disease by S0_2 inhalation method.Chinese medical jurnal.2000,113(3):213-216
[18]Zaher C,Halbert R,Dubois R,et al.Smoking-related diseases:the importance of COPD.Int J Tuberc Lung Dis.2004,8(12):1423-1428
[19]Nagai A.Apoptosis in chronic obstructive pulmonary disease.Nippon Rinsho.2003,61(12):2126-2132
[20]Di Stefano A,Capelli A,Lusuardi M,et al.Severity of airflow limitation is associated with severity of airway inflammation in smokers.[J].Am J Respir Crit Care Med.1998,158:1277-1285
[21]宋一平,崔德健,茅培英.慢性阻塞性肺病大鼠模型的建立及药物干预的影响.军医进修学院学报.2001,22(2):99-102
[22]李红梅,崔德健等.熏香烟加气管注内毒素和单纯熏香烟法建立大鼠COPD模型.中国病理生理杂志.2002,18(7):808-812
[23]Vernooy JH,Dentener MA,van Suylen RJ,et al.Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent Pathology.Am J Respir Cell Mol Biol,2002,26(1):152～159.
[24]Finkelstein R,Fraser RS,Ghezzo H,et al.Alveolar inflammation and its relation to emphysema m smokers[J].Am:J Respir Crit Care Med.1995,152:1 666～1672
[25]Snetta M Gorbnn A Di Stefano A,et al.CD8+T lymphocytes in the peripheral airway of smokers with chronic pulmonary disease(Abstract)[J].Am J Respir Crit care Med,1998,157:A794
[26]Mim vitlles M.Exacerbation of chronic obstructive pulmonary disease when are bacterial important Eur Respir J,2002,20:36-39
[27]O'Reilly T.Relevance of animal models for chronic bacterial airway infections in humans.Am J Respir Crit Care Med.1995,11:2101-2108.
[28]Cash HA,Woods DE,McCullough B,et al.A rat model of chronicrespiratory infection with Pseudomonas aeruginosal Am Rev RespirDis.1979,119(3):453
[29]Slater LN. A rat model of prolonged pulmonary infection due to nontypable Haemophilus influenzae.Am Rev Respir Dis.1990,142:1429～1435.
[30]Pearson JP,Feldman M,Iglewski BH.Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection.Infect Immun.2000,68(7):4331～4334
[31]Murphy TF,Brauer AL,Schiffinacher AT,et al.Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004,170:266-272.
[32]Sethi S,Evans N,Grant BJB,et al.Acquisition of a new bacterial strain and occurrence of exacerbations of chronic obstructive pulmonary disease.N Engl J Med.2002,347:465-471.
[33]Kobayashi H.Biofilm disease,its clinical manifestation and therapeutic possibilities of macrolides.Am J med.1995,99(6A):26S-28S
[34]Post JC.Direct evidence of bacterial biofilms in otitis media.Laryngoscope.2001,111(12):2083-2094.
[35]ChicurelM.Bacterial biofilms and infections- slimebusters[J].Nature.2001,408:284-286.
[36]Hoiby N,Krogh Johansen H,Moser C,et al.Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth[J].Microbes Infect.2001,3(1):23-35.
[37]Casterton JW,Veeh R,ShirtliffM,et al The application ofbiofilm science to the study and control of chronic infections[J].J Chin Invest.2003,112:1466-147
[38]Costerton J W,Stewart PS,Greenberg EP.Bacterial biofilms:a common cause of persistent infections[J].Science.1999,284(5418):1318-1322.
[39]Morikawa T,Kadota,J Kohno S,et al.Superoxide dismutase in alveolar macrophages from patients with diffuse bronchiolitis.Respiration.2000,67(5):546-51.
[40]Takeoka K,Ichimiya T,Yamasaki T,et al.The in vitro effect ofmacrolides on the interaction of human polymorphonuclear leukocyteswith Pseudomonas aeruginosa in biofilm.Chemotherapy.1998,44:190-197.
[41]胡翠燕.阿奇霉素治疗60例社区获得性肺炎临床分析.临床医学,2006,26:61
[42]Heinrich P C,Castell JV,Andus T,et al.Interleukin-6 and acute phase response.[J]Biochem J.1990,265:621-636.
[43]Gonzalez BE,Mercado CK,Johnson L,et al.Early markers of late-onset sepsis in premature neonates:clinical,hematological and cytokine profile.J Perinat Med.2003,31:60-8.
[44]Manuel LC,Jose PB,Eloi EB,et al.Clinical and pathologic predictors of outcome in thymomaa-ssociated myasthenia gravis[J].Ann Thorac urg.2003,76(5):1643 1649
[45]Li Y,Du B,Pan JQ,et al.Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells.Zhejiang Univ Sci B.2006,7:899-905.
[46]Khair OA,Devalia JL,Abdelaziz MM,et al.Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6,IL-8,TNF- a and expression of ICAM-1 in cultured human bronchial epithelial cells.Eur Respir J.1994,7:2109-2116.
[47]Bruee B,et al.The biology of cachectin TNF a primary mediator of the host response.Ann Res Immunol.1989,7:625-655.
[48]Groeneweqen KH,Dentener MA,Wouters EF.Longitudinal follow-up of systemic inflammation after acute exacerbations of COPD.Respir Med,2007,(11):2409-2415.
[49]李玉珊,慢性阻塞性肺病合并肺部感染患者IL-6、IL-8、TNF-α测定的临床意义.医学文选.2003 5(22):636-637
[50]向成玉,邓正华,邓剑.IL-4及IL-8检测在慢性阻塞性肺疾病中的意义[J].实用预防医学.2006,13(1):66-68.
[51]He JQ,Forman MG,Shumansky K,et al.Associations of IL6 polymorphisms with lung function decline and COPD,Th0rax.2009,4
[52]Cigana C,Nicolis E,Pasetto M,Assael BM et al,Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cell.Biochem Biophys Res Commun.2006,(4):977-982
[53]Tsai,W.C.,M.L.Rodriguez,K.S.Young,et al.Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection.Am.J.Respir.Crit.Care Med.2004,170:1331-1339
[54]Olsen,K.M.,G.San Pedro,L.P.Gann,P.O.Gubbins,D.M.Halinski,and G.D.Campbell,Jr.Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses Antimicrob.Agents Chemother.1996,40:2582-2585
[55]Wilms EB,Touw DJ,Heijerman HG,Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit.2006,28(2):219-25
[56]Tsai WC,hershenson MB,Zhou Y et al,Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice,Inflamm Res,2009,5,(7)Epub ahea of print.
[57]Baumann U,King M,App EM,et al,Long term azithromycin therapy in cystic fibrosis patients:a study on drug levels and sputum properties.Can Respir J.2004 11(2):151-155.
[58]Pradeep AR,Sagar SV,Daisy H,Clincal and microbiologic effects of subgingivally delivered 0.5% azithromycin in the treatment of chronic periodontitis,J Periodontol.2008,(11):2125-2135.
[1]Rammaert B,Ader F,Nseir S.Ventilator-associated pneumonia and chronic obstructive pulmonary disease,Rev Mal Respir.2007 24(10):1285-98
[2]Brum G,Melo R,Monteiro F,et al.Ventilator-associated pneumonia (VAP)[J].Eur Respir J,2004,24:5475.
[3]FelclinanlnglisTJJ.New insights into the pathogenesis of ventilator associated pneumonia.J Hosp Infect,1995,30:409-413
[4]Murphy TF,Brauer AL,Schiffmacher AT,et al.Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004;170:266-272.
[5]Sethi S,Evans N,Grant BJB,et al.Acquisition of a new bacterial strain and occurrence of exacerbations of chronic obstructive pulmonary disease.N Engl J Med,2002;347:465-471.
[6]Brum G,Melo R,Monteiro F,et al.Ventilator-associated pneumonia(VAP)[J].Eur Respir J,2004,24:54-75
[7]李影林.临床微生物学及检验.人民卫生出版社,1995;673
[8]Cosio M,Chezzo H,Hogg JC.et al.The relations between structural changes in small airways and pulmonary function tests.N Engl J Med.1978,298(23):1277-1281.
[9]Rammaert B,Ader F,Nseir S.Ventilator-associated pneumonia and chronic obstructive pulmonary disease,Rev Mal Respir.2007 24(10):1285-98
[10]Cook D.Ventilator associated pneumonia perspective on the burden of illness.Intensive Care Med,2000,26 suppl:s371—s377.5 Morehead RS,Pinto SJ.Ventilator-associated pneumonia.Arch IntemMed,2000,160(13):1926-1936.6
[11]Saad Nseir,MD;Christophe Di Pompeo,Impact of Ventilator-Associated Pneumonia on Outcome in Patients With COPD,CHEST,2005,(128):1650-56
[12]蔡少华、张进川、钱桂生,气管导管生物被膜与复发性铜绿假单胞菌呼吸机相关肺炎的相关性,中华结核和呼吸杂志,2001,6(24):339-34l。
[13]Rello J,Ricart M,Ausina V,Net A,Prats G.Pneumonia due to Haemophihus influenzae among mechanically ventilated patients.Incidence,outcome,and risk factors.Chest 1992;102(5):1562-1565.
[14]Rello J,Esandi ME,Mariscal D,Gallego M,Domingo C,VallesJ.Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease:report of eight cases and review.Clin Infect Dis 1998;26(6):1473-1475.
[15]David R Park,The Microbiology of Ventilator-Associated Pneumonia,RESPIRATORY CARE.JUNE 2005 VOL 50 NO 6,742-766
[16]Vandecasteele S J,Peetermans W E,Merckx R,et al.Expression ofbiofillm associalted genes in Straphylococcus epidermidis during in vitro and in vivo foreign bodvi nfections.[J]Infect Dis.2003.188,:730-737
[17]阎锡新李帅齐天杰等,机械通气患者气管导管内生物被膜生成及病原分析,中华结核和呼吸杂志,2008,7(31):501-504
[18]Berra L,De Marchi L,Yu ZX,Laquerriere P,Baccarelli A,Kolobow T.Endotracheal tubes coatedwith antiseptics decrease bacterial colonization of the ventilator circuits,lungs,and endotracheal tube Anesthesiology.2004,100:1446-1456.
[19]Marin H.Kollef,Bekele Afessa,Antonio Anzuetlo et a,Silver-Coated Endotracheal Tubes and Incidenceof Ventilator-Associated Pneumonia JAMA,2008:805-813.
[20]安树昌、阎锡新、张淑哲等,气管导管局部用药对生物被膜形成及医院内下呼吸道感染的影响.中华结核和呼吸杂志2006,1(29):66-68
[21]Wilms EB,Touw DJ,Heijerman HG,Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit,2006,28(2):219-25
[22]张梅,王睿等.大环内酯类抗菌药物对加替沙星透过细菌生物被膜的影响.中华医院感染学杂志,2005,7(15):725-27
[1]Hasting J W,Nealson K H.Bacterial biolum inescence.Annu Rev Microbiol,1977,31:549-595.
[2]C.Water,B.L.Bassler.Quorum sensing:cell to cell communication in bacteria.Annu Rev Cell Dev Biol,2005,21:319-346.
[3]Keller,-L;Surette,-M-G.Communication in bacteria:an ecological and evolutionary perspective.Nat Rev Microbiol,2006,4:249-258.
[4]SchauderS,BasslerBL.The language of bacteria.Genes Development,2001,15:1468-1480.
[5]C.Fuqua,M.R.Parsek,E.P.Greenberg.Regulation of gene expression by cell-to-cell communication:acyl-homoserine lactone quorum sensing.Annu Rev Genet,2001,35:439-468.
[6]Eber L,Molin S,Givskov M.Surface motility of serratia liquefaciens MG1.J Bacteriol,1999,181:1703-1712.
[7]E.Deziel;Lepine,-F;Milot,-S;et al.Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines(HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication.Proc Natl Acad Sci USA,2004,101:1339-1344.
[8]L.M.Mashburn,M.Whiteley.Membrane vesicles traffic signals and facilitate group activities in a prokaryote.Natur,2005,437:422-425.
[9]Kay E,Humair B,Denervaud V,Riedel K,et al.Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa.J Bacteriol,2006,188:6026-6033.
[10]Xavier K B,Bassler B L.LuxS quorum sensing more than just a numbers game.Curr Opin Microbiol,2003,6:191-197.
[11]Vuong C,Gerke C,Somerville G A,et al.Quorum-sensing control of biofilm factor in staphylococcus epidermidis.J Infect Dis,2003,188:706-718.
[12]Taga ME,Bassler BL.Communication among bacteria.Proc Nat Acad Sci(suppl 2),2003,100:1549-1554.
[13]Ben-Jacob-E,Becker-I,Shapira-Y,et al.Bacterial Linguistic communication and social intelligence.Trends Microbiol,2004,12:366-372.
[14]Strurme MHJ,Kleeebezem M,Nalayama J,et al.Cell to cell communication by autoinducing peptides in grampositive bacteria.Antonie van Leewenhoek,2002,81:233-243.
[15]Andrew Camilli,Bonnie L.Bassler.Bacterial Small-Molecule Signaling Pathways,Science,2006,311:1113-1116
[16]K.B.Xavier,B.L.Bssler.Interference with AI-2-mediated bacterial cell-cell communication.Nature,2005,437:750-753.
[17] Robert B,Joseph R,Lannuzzo,Diana R.Levine, et al. Bacterial Communication("quorum sensing")Via Ligands and Recepors:A Novel Pharmacologic Target for the Design of Antibiotic Drugs.Journal of Pharmacology and Experimental Therapeutics,2005,312:417-423.
[2]Costerton,JW,G Geesey,and GK Cheng.How bacteria stick[J].Sci Am.1978,238:86-95.
[3]唐子圣,朱敏,刘正.抗菌剂作用后变形链球菌生物膜细胞活力观察.临床口腔医学杂志.2007,7(21):387-389
[4]小林宏行.细菌菌膜的基础与临床[J].中国临床药理学杂志,1999;15(4):299-307.
[5]Katateda,Rachel Comte,Jean-Claude Pechere et al.Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa,ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2001(6):1930-1933.
[6]张梅,王睿等.大环内酯类抗菌药物对加替沙星透过细菌生物被膜的影响.中华医院感染学杂志,2005,7(15):725-27
[7]Post JC.Direct evidence of bacterial biofilms in otitis media.Laryngoscope.2001,111(12):2083-2094.
[8]修清玉,方正,赖国祥等.改良流感嗜血杆菌培养基的实验研究与评价.中华医学检验杂志.1998,21(3):161-163.
[9]Murphy TF,Kirkham C.Biofilm formation by nontypeable Haemophilus influenzae:strain variability,outer membrane antigen expression and role of pili.BMC Microbiol.2002,(2):7.
[10]Clinical and Laboratory Standards Institute.Performance standards for antimicrobial susceptibility testing,seventeenth informational supplement.M100-S17.Wayne,PA:CLSI;2007.
[11]Tomoku I,Kaori T,Kazufiumi H,et al.The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro.Chemother,1996,42:186-191.
[12]Potera C.Forging a link between biofilm and disease [J].Science,1999,283:1873
[13]Sugita J,Yokoi N,Fullwood NJ,et al.The Detection of Bacterial biofilms in Punctal Plug Holes[J].Coenea.2001,20:362-365.
[14]Hall-Stoodley L,Hu FZ,Gieseke A.Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.JAMA.2006 Jul 12;296(2):202-11.
[15]Martin Kuehn,Martina Hausner,Hans-Joach in Bungartz,etal.Automated confocal laser scanning microscopy and semiautomated miage processing for analysis of biofilms[J].Appl Environ Microbiol 1998,64:4115-4127.
[16]冯丽萍.细菌生物膜[A].见:徐建国.分子医学细菌学[M].第1版.北京:科学出版,2000:173-178
[17]Sutherland I W.The biofilm matrix an immobilized but dynamic microbial environment[J].Trends Microbiol.2001,9:222-227
[18]Sethi S.Pathogenesis and treatment of acute exacerbations of chronic obstructive pulmonary disease.Seminars in Respiratory Mediators in the Critical Care Medicine.2005,26:192-201.
[19]Bayston R,Rodgers J.Production of extra-cellular slime by Staphylococcus epidermidis:during stationary phase of growth:its association with adherence to implantable devices.J Clin Pathol,1990,43:866-870.
[20]Christensen GD,Simpson WA,Bisno AL,et al.Adherence of slime-producing strains of Staphylococcus epidermidis to smooth surfaces.Infect Immun.1982,37:318-326
[21]Hlentzer M,Givskov M,Eber L.Quorum sensing in biofilms:Gossip in slime city[M].Washington DC:American Society for Microbiology Press,2004:118
[22]Davies DG,Parsek MR,Pearson JP,et al.The involvement of cell-to-cell signals in the development of a bacterial biofilm[J].Science.1998,280:295-301
[23]Shih Pei-Ching,Huang Ching -Tsan.Effects of quorum-sensing deficiency on Pseudomonas aeruginosa biofilm formation and antibiotic resistance[J].J Antimicrob Chemother,2002,49:309-14
[24]Walters MC,Roe F,Bugnicourt A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginose biofilm to ciprofloxacin and tobramycin.Atimicrobial Agents and Chemo-therapy.2003,47(1):317-323.
[25]Thien-Fah CM.O' Toole GA.Mechanisms of biofilm resistance to antimicrobial agents.Trends in Microbiol.2001,9(1):34-39.
[26]Timothy D.Stamer,Joshua D.Shrout,Matthew R.Parsek,Peter C.Appelbaum,and GunHee Kim,Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation andDiminish Established Biofilms. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2008,1(52):137-145
[27]Hoffman LR,David A.D Argenio,Michae J.MacCoss.Aminoglycoside antibiotics induce bacterial biofilm formation. Nature. 2005, 436(7054):1171-1175.
[28]Tateda,K.,Y.Ishii,Y.Hirakata,T.Matsumoto,A.Ohno,and K.Yamaguchi.Profiles of outer membrane proteins and lipopolysaccharide of Pseudomonas aeruginosa grown in the presence of sub-MICs of macrolide antibiotics and their relation to enhanced serum sensitivity. J. Antimicrob.Chemother.1994.34:931-942.
[29]Gillis.R.J and B.H.Iglewski.Azithromycin retards Pseudomonas aeruginosa biofilm formation.J.Clin.Microbiol.2004,42:5842-5845.
[30]Timothy D,Starner Joshua D,Shrout,Matthew R.Parsek,et al.Subinhibitory Concentrations of Azithromycin Decrease Nontypeable Haemophilus influenzae Biofilm Formation and Diminish Established Biofilms.Antimicrobial Agents and Chemotherary.2008,1(52).137-145
[31]C.Water,B.L.Bassler.Quorum sensing:cell-to-cell communication in bacteria.Annu.Re v.Cell Dev.Biol.2005,(21):319-346
[32]Wlters M C,Roe F,Bugnicout A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin[J]·Antimicrob Agents Chemother.2003,47:317～323
[33]SouliM, and H.GIAMarellou.Effects of slime produced by clinical isolates of coagulase-negative staphylococcion activities of various antimicrobial agents[J].antimicrob Agents Chemother,1998 42:939~941
[34] Stewart PS, Costerton JW .Antibiotic resistance in biofilms[J].Lancet.2001,358:135-138.
[35]Costerton J W,Stewart P S.Battling biofilms[J].Sci.2001,285(1):74-81
[36]Wlters M C,Roe F,Bugnicout A,et al.Contributions of antibiotic penetration,oxygen limitation,and low metabolic activity to tolerance of Pseudomonas aeruginosa biofilms to ciprofloxacin and tobramycin[J].Antimicrob Agents Chemother.2003,47:317～32
[37]Karen D,Mcfeters G A,Stewart P S.Biofilm resistance to antimicrobial agents[J]-Microbiology.2000,146:547 ~ 549.
[38]Gordon R,Bachmann S,Patterson TF,et al.Investigation of multidrug efflux pumps in relation to fluconazole resistance in Candida albicans biofilms[J].J Antimicrob Chemother.2002,49:973-980.
[39]Mah T,Pitts B,Pellock B,et al.A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance[J].Nature.2003,426:306-310.
[40]王霞,梁德荣,苗佳．华西医学．2003,18(1):146～1461
[41]C.Water,B.L.Bassler.Quorum sensing:cell-to-cell communication in bacteria.Annu.Re v.Cell Dev.Biol.2005,(21):319-346
[42]Mette E.Skindersoe,Morten Alhede,l Richard Phipps,et al,Effects of Antibiotics on Quorum Sensing in Pseudomonas aeruginosa,Antimicrobial Agents And Chemotherary.2008,(52):3648-3663
[43]Ute Romling and Dorit Amikam.Cyclic di-GMP as a second messenger.Current Opinion in Microbiology.2006,(9):218-228
[44]Balaban NQ,Merrin J,Chait R,et al.Bacterial persistence as a phenotypic switch[J].Science.2004,305(10):1622-25
[45]Baumann U,King M,App EM,et al.Long term azithromycin therapy in cystic fibrosis patients:a study on drug levels and sputum properties.Can Respir J.2004,11(2):151-155.
[46]Spoering AL,Lewis K.Biofilms and planktonic cells of Pseudomonas aeruginosa have similar resistance to killing by antimicrobials[J].J Bacteriol.2001,183(23):6746-6751
[47]Wilms EB,Touw DJ,Heijerman HG.Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit,2006,28(2):219-25
[48]Olsen,K.M,G.San Pedro,L.P.Gann et al.Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses Antimicrob.Agents Chemother.1996,40:2582-2585
[49]Tamura A,Ara T,Imamira Y et al.The effects of antibiotics on in vitro biofilm model of periodontal disease.Eur J Med Res.2008,9:439-445
[1]Sethi S,Murphy TE Bacterial infection in chronic obstructive pulmonary disease in 2000:a State of the Art Review.Clin Microbiol Rew,2001:336-363.
[2]Murphy TF,Brauer AL,Schiffmacher AT,et al.Persistent colonazation by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004,170:266-272.
[3]Buck C.Bundschu J.Gallati H.et al.lnterleukin.6:A soncitive pa.rameter for the early diagnosis of neonatal bacterial infection[J].Pediatrics.1994,93:54-58.
[4]Cree RT,Warnell I,Staunton M,et al.Alveolar and plasma concentrations of interleukin-8 and vascular endothelial growth factor following oesophagectomy[J].Anaesthesia.2004,59(9):867-71.
[5]Katateda,Rachel Comte,Jean-Claude Pechere et al,Azithromycin Inhibits Quorum Sensing in Pseudomonas aeruginosa,ANTIMICROBIAL AGENTS AND CHEMOTHERAPY.2001,(6):1930-1933.
[6]李影林.临床微生物学及检验.人民卫生出版社,1995,673
[7]Ishlda Y.Experimental pneumonia with Pseudomonas aeruginosain immunosuppressed guinea pigs as a model for biofilm-associated infection.Kansen sho gaku Zasshi.1995,69(5):572-81
[8]Cosio M,Chezzo H,Hogg JC.et al.The relations between structural changes in small airways and pulmonary function tests.N Engl J Med.1978,298(23):1277-1281.
[9]Slater LN.A rat model nontypable Haemophilus of prolonged pulmonary infection due to influenzae.Am Rev Respir Dis.1990,142:1429-1435
[10]张永,程德云,王慧,等.慢性阻塞性肺疾病大鼠肺内白细胞介素—8和肿瘤坏死因子-α与气道炎症的关系研究.中国呼吸与危重监护杂志.2003,2(6):355—359.
[11]Murphy TF,Kirkham C.Biofilm formation by nontypeable Haemophilus influenzae:strain variability,outer membrane antigen expression and role of pili. BMC Microbiol.2002,(2):7
[12]Mannino DM.Chronic obstructive pulmonary disease:definition and epidemiology.Respir Care.2003,48:1185-1191
[13]Regional COPD Working Group.COPD prevalence in 12 Asia-Pacific countries and regions:projections based on the COPD prevalence estimation model.Respirology.2003,8:192-198
[14]Hoban DJ,Biedenbach DJ,Mutnick AH,et al.Pathogen of occurrence and susceptibility patterns associated with pneumonia in hospitalized patients in North America:results of the SENTRY Antimicrobial Surveillance Study(2000)[J].Diagn Microbiol Infect Dis.2003,45(4):279-285.
[15]Hall-Stoodley L,Hu FZ,Gieseke A.Direct detection of bacterial biofilms on the middle-ear mucosa of children with chronic otitis media.JAMA.200612(2):202-11.
[16]Andrew Churg,Manuel Cosio,and Joanne L.Wright.Mechanisms of cigarette smoke-induced COPD:insights from animal models.Am J Physiol Lung Cell Mol Physiol.2008,294:L612-L631
[17]XU Jianying,et al.Establishment and pathological study of models of chronic obstructive pulmonary disease by S0_2 inhalation method.Chinese medical jurnal.2000,113(3):213-216
[18]Zaher C,Halbert R,Dubois R,et al.Smoking-related diseases:the importance of COPD.Int J Tuberc Lung Dis.2004,8(12):1423-1428
[19]Nagai A.Apoptosis in chronic obstructive pulmonary disease.Nippon Rinsho.2003,61(12):2126-2132
[20]Di Stefano A,Capelli A,Lusuardi M,et al.Severity of airflow limitation is associated with severity of airway inflammation in smokers.[J].Am J Respir Crit Care Med.1998,158:1277-1285
[21]宋一平,崔德健,茅培英.慢性阻塞性肺病大鼠模型的建立及药物干预的影响.军医进修学院学报.2001,22(2):99-102
[22]李红梅,崔德健等.熏香烟加气管注内毒素和单纯熏香烟法建立大鼠COPD模型.中国病理生理杂志.2002,18(7):808-812
[23]Vernooy JH,Dentener MA,van Suylen RJ,et al.Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent Pathology.Am J Respir Cell Mol Biol,2002,26(1):152～159.
[24]Finkelstein R,Fraser RS,Ghezzo H,et al.Alveolar inflammation and its relation to emphysema m smokers[J].Am:J Respir Crit Care Med.1995,152:1 666～1672
[25]Snetta M Gorbnn A Di Stefano A,et al.CD8+T lymphocytes in the peripheral airway of smokers with chronic pulmonary disease(Abstract)[J].Am J Respir Crit care Med,1998,157:A794
[26]Mim vitlles M.Exacerbation of chronic obstructive pulmonary disease when are bacterial important Eur Respir J,2002,20:36-39
[27]O'Reilly T.Relevance of animal models for chronic bacterial airway infections in humans.Am J Respir Crit Care Med.1995,11:2101-2108.
[28]Cash HA,Woods DE,McCullough B,et al.A rat model of chronicrespiratory infection with Pseudomonas aeruginosal Am Rev RespirDis.1979,119(3):453
[29]Slater LN. A rat model of prolonged pulmonary infection due to nontypable Haemophilus influenzae.Am Rev Respir Dis.1990,142:1429～1435.
[30]Pearson JP,Feldman M,Iglewski BH.Pseudomonas aeruginosa cell-to-cell signaling is required for virulence in a model of acute pulmonary infection.Infect Immun.2000,68(7):4331～4334
[31]Murphy TF,Brauer AL,Schiffinacher AT,et al.Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004,170:266-272.
[32]Sethi S,Evans N,Grant BJB,et al.Acquisition of a new bacterial strain and occurrence of exacerbations of chronic obstructive pulmonary disease.N Engl J Med.2002,347:465-471.
[33]Kobayashi H.Biofilm disease,its clinical manifestation and therapeutic possibilities of macrolides.Am J med.1995,99(6A):26S-28S
[34]Post JC.Direct evidence of bacterial biofilms in otitis media.Laryngoscope.2001,111(12):2083-2094.
[35]ChicurelM.Bacterial biofilms and infections- slimebusters[J].Nature.2001,408:284-286.
[36]Hoiby N,Krogh Johansen H,Moser C,et al.Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth[J].Microbes Infect.2001,3(1):23-35.
[37]Casterton JW,Veeh R,ShirtliffM,et al The application ofbiofilm science to the study and control of chronic infections[J].J Chin Invest.2003,112:1466-147
[38]Costerton J W,Stewart PS,Greenberg EP.Bacterial biofilms:a common cause of persistent infections[J].Science.1999,284(5418):1318-1322.
[39]Morikawa T,Kadota,J Kohno S,et al.Superoxide dismutase in alveolar macrophages from patients with diffuse bronchiolitis.Respiration.2000,67(5):546-51.
[40]Takeoka K,Ichimiya T,Yamasaki T,et al.The in vitro effect ofmacrolides on the interaction of human polymorphonuclear leukocyteswith Pseudomonas aeruginosa in biofilm.Chemotherapy.1998,44:190-197.
[41]胡翠燕.阿奇霉素治疗60例社区获得性肺炎临床分析.临床医学,2006,26:61
[42]Heinrich P C,Castell JV,Andus T,et al.Interleukin-6 and acute phase response.[J]Biochem J.1990,265:621-636.
[43]Gonzalez BE,Mercado CK,Johnson L,et al.Early markers of late-onset sepsis in premature neonates:clinical,hematological and cytokine profile.J Perinat Med.2003,31:60-8.
[44]Manuel LC,Jose PB,Eloi EB,et al.Clinical and pathologic predictors of outcome in thymomaa-ssociated myasthenia gravis[J].Ann Thorac urg.2003,76(5):1643 1649
[45]Li Y,Du B,Pan JQ,et al.Up-regulation interleukin-6 and interleukin-8 by activated protein C in lipopolysaccharide-treated human umbilical vein endothelial cells.Zhejiang Univ Sci B.2006,7:899-905.
[46]Khair OA,Devalia JL,Abdelaziz MM,et al.Effect of Haemophilus influenzae endotoxin on the synthesis of IL-6,IL-8,TNF- a and expression of ICAM-1 in cultured human bronchial epithelial cells.Eur Respir J.1994,7:2109-2116.
[47]Bruee B,et al.The biology of cachectin TNF a primary mediator of the host response.Ann Res Immunol.1989,7:625-655.
[48]Groeneweqen KH,Dentener MA,Wouters EF.Longitudinal follow-up of systemic inflammation after acute exacerbations of COPD.Respir Med,2007,(11):2409-2415.
[49]李玉珊,慢性阻塞性肺病合并肺部感染患者IL-6、IL-8、TNF-α测定的临床意义.医学文选.2003 5(22):636-637
[50]向成玉,邓正华,邓剑.IL-4及IL-8检测在慢性阻塞性肺疾病中的意义[J].实用预防医学.2006,13(1):66-68.
[51]He JQ,Forman MG,Shumansky K,et al.Associations of IL6 polymorphisms with lung function decline and COPD,Th0rax.2009,4
[52]Cigana C,Nicolis E,Pasetto M,Assael BM et al,Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cell.Biochem Biophys Res Commun.2006,(4):977-982
[53]Tsai,W.C.,M.L.Rodriguez,K.S.Young,et al.Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection.Am.J.Respir.Crit.Care Med.2004,170:1331-1339
[54]Olsen,K.M.,G.San Pedro,L.P.Gann,P.O.Gubbins,D.M.Halinski,and G.D.Campbell,Jr.Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses Antimicrob.Agents Chemother.1996,40:2582-2585
[55]Wilms EB,Touw DJ,Heijerman HG,Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit.2006,28(2):219-25
[56]Tsai WC,hershenson MB,Zhou Y et al,Azithromycin increases survival and reduces lung inflammation in cystic fibrosis mice,Inflamm Res,2009,5,(7)Epub ahea of print.
[57]Baumann U,King M,App EM,et al,Long term azithromycin therapy in cystic fibrosis patients:a study on drug levels and sputum properties.Can Respir J.2004 11(2):151-155.
[58]Pradeep AR,Sagar SV,Daisy H,Clincal and microbiologic effects of subgingivally delivered 0.5% azithromycin in the treatment of chronic periodontitis,J Periodontol.2008,(11):2125-2135.
[1]Rammaert B,Ader F,Nseir S.Ventilator-associated pneumonia and chronic obstructive pulmonary disease,Rev Mal Respir.2007 24(10):1285-98
[2]Brum G,Melo R,Monteiro F,et al.Ventilator-associated pneumonia (VAP)[J].Eur Respir J,2004,24:5475.
[3]FelclinanlnglisTJJ.New insights into the pathogenesis of ventilator associated pneumonia.J Hosp Infect,1995,30:409-413
[4]Murphy TF,Brauer AL,Schiffmacher AT,et al.Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease.Am J Respir Crit Care Med.2004;170:266-272.
[5]Sethi S,Evans N,Grant BJB,et al.Acquisition of a new bacterial strain and occurrence of exacerbations of chronic obstructive pulmonary disease.N Engl J Med,2002;347:465-471.
[6]Brum G,Melo R,Monteiro F,et al.Ventilator-associated pneumonia(VAP)[J].Eur Respir J,2004,24:54-75
[7]李影林.临床微生物学及检验.人民卫生出版社,1995;673
[8]Cosio M,Chezzo H,Hogg JC.et al.The relations between structural changes in small airways and pulmonary function tests.N Engl J Med.1978,298(23):1277-1281.
[9]Rammaert B,Ader F,Nseir S.Ventilator-associated pneumonia and chronic obstructive pulmonary disease,Rev Mal Respir.2007 24(10):1285-98
[10]Cook D.Ventilator associated pneumonia perspective on the burden of illness.Intensive Care Med,2000,26 suppl:s371—s377.5 Morehead RS,Pinto SJ.Ventilator-associated pneumonia.Arch IntemMed,2000,160(13):1926-1936.6
[11]Saad Nseir,MD;Christophe Di Pompeo,Impact of Ventilator-Associated Pneumonia on Outcome in Patients With COPD,CHEST,2005,(128):1650-56
[12]蔡少华、张进川、钱桂生,气管导管生物被膜与复发性铜绿假单胞菌呼吸机相关肺炎的相关性,中华结核和呼吸杂志,2001,6(24):339-34l。
[13]Rello J,Ricart M,Ausina V,Net A,Prats G.Pneumonia due to Haemophihus influenzae among mechanically ventilated patients.Incidence,outcome,and risk factors.Chest 1992;102(5):1562-1565.
[14]Rello J,Esandi ME,Mariscal D,Gallego M,Domingo C,VallesJ.Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease:report of eight cases and review.Clin Infect Dis 1998;26(6):1473-1475.
[15]David R Park,The Microbiology of Ventilator-Associated Pneumonia,RESPIRATORY CARE.JUNE 2005 VOL 50 NO 6,742-766
[16]Vandecasteele S J,Peetermans W E,Merckx R,et al.Expression ofbiofillm associalted genes in Straphylococcus epidermidis during in vitro and in vivo foreign bodvi nfections.[J]Infect Dis.2003.188,:730-737
[17]阎锡新李帅齐天杰等,机械通气患者气管导管内生物被膜生成及病原分析,中华结核和呼吸杂志,2008,7(31):501-504
[18]Berra L,De Marchi L,Yu ZX,Laquerriere P,Baccarelli A,Kolobow T.Endotracheal tubes coatedwith antiseptics decrease bacterial colonization of the ventilator circuits,lungs,and endotracheal tube Anesthesiology.2004,100:1446-1456.
[19]Marin H.Kollef,Bekele Afessa,Antonio Anzuetlo et a,Silver-Coated Endotracheal Tubes and Incidenceof Ventilator-Associated Pneumonia JAMA,2008:805-813.
[20]安树昌、阎锡新、张淑哲等,气管导管局部用药对生物被膜形成及医院内下呼吸道感染的影响.中华结核和呼吸杂志2006,1(29):66-68
[21]Wilms EB,Touw DJ,Heijerman HG,Pharmacokinetics of azithromycin in plasma,blood,polymorphonuclear neutrophils and sputum during long-term therapy in patients with cystic fibrosis.The Drug Monit,2006,28(2):219-25
[22]张梅,王睿等.大环内酯类抗菌药物对加替沙星透过细菌生物被膜的影响.中华医院感染学杂志,2005,7(15):725-27
[1]Hasting J W,Nealson K H.Bacterial biolum inescence.Annu Rev Microbiol,1977,31:549-595.
[2]C.Water,B.L.Bassler.Quorum sensing:cell to cell communication in bacteria.Annu Rev Cell Dev Biol,2005,21:319-346.
[3]Keller,-L;Surette,-M-G.Communication in bacteria:an ecological and evolutionary perspective.Nat Rev Microbiol,2006,4:249-258.
[4]SchauderS,BasslerBL.The language of bacteria.Genes Development,2001,15:1468-1480.
[5]C.Fuqua,M.R.Parsek,E.P.Greenberg.Regulation of gene expression by cell-to-cell communication:acyl-homoserine lactone quorum sensing.Annu Rev Genet,2001,35:439-468.
[6]Eber L,Molin S,Givskov M.Surface motility of serratia liquefaciens MG1.J Bacteriol,1999,181:1703-1712.
[7]E.Deziel;Lepine,-F;Milot,-S;et al.Analysis of Pseudomonas aeruginosa 4-hydroxy-2-alkylquinolines(HAQs) reveals a role for 4-hydroxy-2-heptylquinoline in cell-to-cell communication.Proc Natl Acad Sci USA,2004,101:1339-1344.
[8]L.M.Mashburn,M.Whiteley.Membrane vesicles traffic signals and facilitate group activities in a prokaryote.Natur,2005,437:422-425.
[9]Kay E,Humair B,Denervaud V,Riedel K,et al.Two GacA-dependent small RNAs modulate the quorum-sensing response in Pseudomonas aeruginosa.J Bacteriol,2006,188:6026-6033.
[10]Xavier K B,Bassler B L.LuxS quorum sensing more than just a numbers game.Curr Opin Microbiol,2003,6:191-197.
[11]Vuong C,Gerke C,Somerville G A,et al.Quorum-sensing control of biofilm factor in staphylococcus epidermidis.J Infect Dis,2003,188:706-718.
[12]Taga ME,Bassler BL.Communication among bacteria.Proc Nat Acad Sci(suppl 2),2003,100:1549-1554.
[13]Ben-Jacob-E,Becker-I,Shapira-Y,et al.Bacterial Linguistic communication and social intelligence.Trends Microbiol,2004,12:366-372.
[14]Strurme MHJ,Kleeebezem M,Nalayama J,et al.Cell to cell communication by autoinducing peptides in grampositive bacteria.Antonie van Leewenhoek,2002,81:233-243.
[15]Andrew Camilli,Bonnie L.Bassler.Bacterial Small-Molecule Signaling Pathways,Science,2006,311:1113-1116
[16]K.B.Xavier,B.L.Bssler.Interference with AI-2-mediated bacterial cell-cell communication.Nature,2005,437:750-753.
[17] Robert B,Joseph R,Lannuzzo,Diana R.Levine, et al. Bacterial Communication("quorum sensing")Via Ligands and Recepors:A Novel Pharmacologic Target for the Design of Antibiotic Drugs.Journal of Pharmacology and Experimental Therapeutics,2005,312:417-423.