老年住院患者口咽部念珠菌定植状况及菌种分布调查

目的调查老年住院患者口咽部念珠菌定植状况及菌种分布特点,为有效预防念珠菌感染提供参考。方法对解放军第44医院收治的894例住院患者口咽部念珠菌定植状态进行调查分析。结果894例住院患者口咽部标本共培养出念珠菌121株,念珠菌定植率为13．5％,老年患者的定植率高于非老年患者。念珠菌定植以白色念珠菌所占比例最大,占74．5％。年龄≥80岁、肺部基础疾病的存在及使用抗菌药物患者口咽部念珠菌定植率高于普通患者,两者比较差异有统计学意义（P〈0．05）。结论老年患者口咽部念珠菌定植率较高,菌种分布以白色念珠菌最为常见。念珠菌定植与患者年龄、肺部基础疾病的存在及抗菌药物使用情况密切相关。     

FKS与光滑念珠菌棘白菌素耐药

近年来,光滑念珠菌侵入性感染及其耐棘白菌素治疗失败的病例不断增多,深入研究其耐药机制十分有必要。Fks突变在光滑念珠菌棘白菌素耐药发生的过程中有着极其重要的地位,其与棘白菌素的MIC值及体内治疗结果密切相关,且有很多因素可以对Fks突变的发生及其作用产生影响。     

光滑念珠菌的毒力表达特征研究进展

引言由于免疫功能低下的患者的数量增加和抗生素的广泛使用,真菌感染已成为医院中的重要问题,目前真菌引起的感染已影响到全世界数百万人口,根据统计调查,每年约有140万人死于真菌感染[1];最新的全球监视和多中心研究表明,超过90%的侵入性真菌感染(invasive fungal infections,IFI)的病因是由念珠菌属(Candida spp.)感染引起的[2-3]。其中,光滑念珠菌(Candida glabrata)占所有病例的近15%,且其占比有稳步上升的趋势,是仅次于白念珠菌(Candida albicans)的第二大常见的念珠菌病的病原体[4-6]。     

光滑念珠菌致病性和耐药机制研究进展

<正>光滑念珠菌(Candida glabrata)是一种黏膜表面定植的机会致病菌,可引起侵袭性念珠菌病。光滑念珠菌是仅次于白念珠菌的念珠菌病相关第二大病原体^[1]。其高发病率与HIV、肿瘤、糖尿病患者数量的增加有关,人口老龄化和侵入性治疗也会增加感染风险。光滑念珠菌与致病性相关的毒力因子包括对宿主细胞及医疗器械黏附性、生物膜形成、逃避宿主防御、复制性老化、分泌水解酶(包括蛋白酶、磷脂酶、酯酶和溶血素等)等,在感染过程中发挥重要作用^[2]。此外,光滑念珠菌对抗真菌药物具有普遍耐受性,常常导致治疗的失败^[3]。由于致病性与耐药性的完美组合,使光滑念珠菌感染呈现出“发病率高、病死率高、耐药率高”的现象,需引起足够重视^[4]。本文就光滑念珠菌致病相关毒力因子和耐药机制研究进展进行综述。     

抗白念珠菌感染的疫苗及抗体研究进展

白念珠菌是与人类共生的条件致病真菌,能引起免疫力低下患者皮肤黏膜和全身系统性持续感染.系统性念珠菌病是引起免疫力低下患者死亡的主要原因之一.由于临床缺乏念珠菌病的早期诊疗手段、可用的抗真菌药物种类有限且毒副作用大、耐药菌株越来越普遍、新药研发难度大等因素,抗真菌治疗依然面临着严峻挑战.目前有较多研究者致力于阐明白念珠菌感染的宿主免疫应答机制,并试图研发抗白念珠菌感染的免疫治疗方法,使免疫治疗有望成为预防和治疗真菌感染的有效手段.该文将几种抗白念珠菌感染的疫苗和抗体研究进展作简要概述,旨在为新型抗白念珠菌感染疫苗及抗体的研究提供参考.     

抗系统性白念珠菌感染的先天性免疫

白念珠菌是引起浅部、深部真菌感染常见的病原菌.先天免疫反应在宿主抗系统性白念珠菌感染中起主导作用.介导宿主抗念珠菌感染的先天性免疫包括一系列真菌识别受体及免疫效应细胞.宿主对系统性白念珠菌感染的免疫反应是决定患者预后的关键.本文就宿主抗系统性白念珠菌感染的先天性免疫机制进行综述.     

光滑念珠菌的生物学、流行病学以及耐药机制研究进展

随着HIV感染患者的增多、器官移植、放疗化疗及抗真菌药物的广泛使用,近年来全世界范围内念珠菌感染趋势发生了明显变化,除白念珠菌外,光滑念珠菌在临床上的检出率逐年增加,在部分国家和地区已成为第二常见的侵袭性念珠菌。光滑念珠菌临床分离株通常对一线抗真菌药物高度耐药,由于目前治疗策略匮乏,其造成的系统感染死亡率可高达50%。为了进一步加深人们对光滑念珠菌的认识,研发遏制其感染的诊疗策略,本文综述了近年来光滑念珠菌的流行病学、毒力因子以及耐药机制等方面的进展,为国内同行深入探究其耐药特性和致病机理提供参考。     

念珠菌菌尿研究进展

念珠菌菌尿现象临床较为常见,其发生危险因素包括严重的基础疾病、高龄、女性、长期抗细菌药物治疗、使用插尿管等侵入性操作、入住重症监护病房、糖尿病等,菌种以白念珠菌为主。社区获得性感染以孕妇和长期卧床者较多。近1个月内使用抗细菌药物和高血糖是临床用于鉴别念珠菌菌尿与细菌菌尿的有用指标。特殊部位（尿道、直肠／造瘘、呼吸道;中央静脉插管等）的真菌培养监测可有助于分析患者发生侵袭性念珠菌病危险性的高低。明确感染时需要抗真菌治疗,一线药物是氟康唑。该文就近年来有关念珠菌菌尿的研究情况作一综述。     

都柏林念珠菌与白念珠菌的实验室鉴别进展

都柏林念珠菌是新命名的可以产生芽管和厚壁孢子的致病念珠菌,常规的实验室检测方法很难将其与白念珠菌相鉴别。本文综述了都柏林念珠菌和白念珠菌的生物形态学特征及形态学、血清学、分子生物学鉴别进展。     

神经内科住院患者感染病原菌分布及其耐药性

目的了解神经内科住院患者感染的病原菌分布特点,产生β-内酰胺酶情况及其药敏特点。方法分析2002年3月至2004年12月白求恩国际和平医院神经内科住院患者临床感染有关的病原学资料。结果共811例住院患者,有71例发生医院内感染,感染率为8．75％;60岁以上老年人51例,占71．8％;基础疾病以脑梗塞为主,有40例（占56．3％）。主要引起肺部感染（49例,69．0％）和尿路感染（20例,28．2％）。共检出103株病原菌,其中：革兰阳性球菌10株（9．71％）,肠杆菌科42株（40．78％）,非发酵菌41株（39．80％）,真菌10株（9．71％）。其中较常见的病原菌为：大肠埃希菌（23．3％）、铜绿假单胞菌（20．4％）、鲍曼不动杆菌（12.6％）、肺炎克雷伯菌（9．71％）、金黄色葡萄球菌（8．7％）、白色念珠菌（6．8％）。革兰阴性杆菌产超广谱β-内酰胺酶占40．9％,AmpC酶占14．5％,金属酶占2．4％。结论大肠埃希菌、铜绿假单胞菌、鲍曼不动杆菌成为神经内科临床感染的主要病原菌,其耐药性不断增强,应当引起足够重视。     

A purine permease in Candida glabrata

Abstract Competition experiments revealed that adenine and guanine were transported by a purine permease in both Candida glabrata 4 and a C. glabrata 4 cytosine permease negative mutant. The C. glabrata 4 cytosine permease negative mutant was isolated using 5-fluorocytosine selection. This mutant no longer transported cytosine, but transported adenine and guanine. A transport system for hypoxanthine was not detected. Hence, in addition to the cytosine permease, a purine permease exists in C. glabrata . This differs from the purine cytosine permeases in Saccharomyces cereuisiae and Candida albicans which transport adenine, cytosine, guanine and hypoxanthine.     

Molecular epidemiology of Candida albicans and Candida glabrata strains isolated from intensive care unit patients in Poland

Over the last decades, Candida spp have been responsible for anincreasing number of infections, especially in patients requiring intensive care.Knowledge of local epidemiology and analysis of the spread of these pathogens isimportant in understanding and controlling their transmission. The aim of this studywas to evaluate the genetic diversity of 31 Candida albicans and17 Candida glabrata isolates recovered from intensive care unitpatients from the tertiary hospital in Krakow between 2011-2012. The strains weretyped by random amplified polymorphic DNA (RAPD) polymerase chain reaction using fiveprimers (CD16AS, HP1247, ERIC-2, OPE-3 and OPE-18). The results of the presentinvestigation revealed a high degree of genetic diversity among the isolates. Noclonal relationship was found among the C. albicans strains, whereastwo C. glabrata isolates were identical. The source ofCandida infection appeared to be mostly endogenous; however, the presenceof two clonal C. glabrata strains suggested the possibility ofcross-transmission of these pathogens. Our study confirmed the high discriminatorypower of the RAPD technique in the molecular typing of Candidaclinical isolates. This method may be applied to the evaluation of transmissionroutes of pathogenic fungi on a local level.     

Silver nanoparticles: influence of stabilizing agent and diameter on antifungal activity against Candida albicans and Candida glabrata biofilms

Aim: The purpose of this work was to evaluate the size‐dependent antifungal activity of different silver nanoparticles (SN) colloidal suspensions against Candida albicans and Candida glabrata mature biofilms. Methods and Results: The research presented herein used SN of three different average sizes (5, 10 and 60 nm), which were synthesized by the reduction of silver nitrate through sodium citrate and which were stabilized with ammonia or polyvinylpyrrolidone. Minimal inhibitory concentration (MIC) assays were performed using the microdilution methodology. The antibiofilm activity of SN was determined by total biomass quantification (by crystal violet staining) and colony forming units enumeration. MIC results showed that all SN colloidal suspensions were fungicidal against the tested strains at very low concentrations (0·4–3·3 μg ml^?1). With regard to biomass quantification, SN colloidal suspensions were very effective only against C. glabrata biofilms, achieving biomass reductions around 90% at a silver concentration of 108 μg ml^?1. In general, all SN suspensions promoted significant log₁₀ reduction of the mean number of cultivable biofilm cells after exposure to silver concentrations at or higher than 108 μg ml^?1. Moreover, the results showed that the particle size and the type of stabilizing agent used did not interfere in the antifungal activity of SN against Candida biofilms. Conclusions: This study suggests that SN have antifungal therapeutic potential, but further studies are still required namely regarding formulation and delivery means. Significance and Impact of the Study: SN may contribute to the development of new strategies for the improvement of oral health and quality of life particularly of the complete denture wearers.     

Candida glabrata and Candida albicans; dissimilar tissue tropism and infectivity in a gnotobiotic model of mucosal candidiasis

Germ-free transgenic epsilon 26 (Tgepsilon26) mice, deficient in both natural killer (NK)- and T-cells, were inoculated (orally) with each of two Candida glabrata (BG2 or BG1003) or Candida albicans (CAF2-1 or SC5314) strains. Candida glabrata- or C. albicans-colonized mice exhibited similar numbers of viable Candida in the alimentary tract. Neither C. glabrata nor C. albicans caused systemic candidiasis of endogenous (alimentary tract) origin. Candida albicans invaded oroesophageal (tongue, palate, esophagus) and keratinized gastric tissues, evoked hyperkeratosis and a prominent, chronic, granulocyte-dominated, inflammatory response in all infected tissues, stimulated the production of splenic granulocytes and was lethal for the mice within 3-5 weeks after oral colonization. The two C. glabrata strains colonized the alimentary tract and penetrated into the keratinized (cardia-antrum) gastric tissues, but in contrast to C. albicans, were unable to infect oroesophageal tissues. Furthermore, C. glabrata strains were not lethal for the Tgepsilon26 mice, and did not evoke an inflammatory response in colonized gastric tissues or stimulate the production of splenic granulocytes. This 'stealth-like' behavior could explain the ability of C. glabrata to persist in infected tissues and survive as a commensal in the alimentary tract.     

Silver colloidal nanoparticles: antifungal effect against adhered cells and biofilms of Candida albicans and Candida glabrata

The aim of this study was to evaluate the effect of silver nanoparticles (SN) against Candida albicans and Candida glabrata adhered cells and biofilms. SN (average diameter 5 nm) were synthesized by silver nitrate reduction with sodium citrate and stabilized with ammonia. Minimal inhibitory concentration (MIC) tests were performed for C. albicans (n = 2) and C. glabrata (n = 2) grown in suspension following the Clinical Laboratory Standards Institute microbroth dilution method. SN were applied to adhered cells (2 h) or biofilms (48 h) and after 24 h of contact their effect was assessed by enumeration of colony forming units (CFUs) and quantification of total biomass (by crystal violet staining). The MIC results showed that SN were fungicidal against all strains tested at very low concentrations (0.4–3.3 μg ml^?1). Furthermore, SN were more effective in reducing biofilm biomass when applied to adhered cells (2 h) than to pre-formed biofilms (48 h), with the exception of C. glabrata ATCC, which in both cases showed a reduction ～90%. Regarding cell viability, SN were highly effective on adhered C. glabrata and respective biofilms. On C. albicans the effect was not so evident but there was also a reduction in the number of viable biofilm cells. In summary, SN may have the potential to be an effective alternative to conventional antifungal agents for future therapies in Candida-associated denture stomatitis.     

In vitro evaluation of adherence of Candida albicans,Candida glabrata,and Streptococcus mutans to an acrylic resin modified by experimental coatings

This study evaluated the effect of experimental coatings, containing zwitterion or hydrophilic monomers, on the adherence of Candida albicans, Candida glabrata, and Streptococcus mutans to an acrylic resin. Acrylic samples (smooth or rough surfaces) were left untreated (control) or coated with one of the following experimental coatings: 3-hydroxypropylmethacrylate (HP) or sulfobetaine methacrylate (S), at concentrations of 25, 30, or 35%. Half of the specimens were coated with saliva. The adhesion test was performed by incubating specimens in C. albicans, C. glabrata, and S. mutans suspensions at 37°C for 90?min. The number of adhered microorganisms was determined by metabolic activity (XTT) and by cell viability (CFU). All coated specimens exhibited lower absorbance and CFU values compared to control specimens. Saliva and roughness did not promote microorganism adherence. An XPS analysis confirmed the modification in the chemical composition of the coatings in the experimental samples. These experimental coatings significantly reduced the adherence of C. albicans, C. glabrata and S. mutans to acrylic resin.     

Proteomic analysis of the pH response in the fungal pathogen Candida glabrata

Micro-organisms must adapt to environmental change to survive, and this is particularly true for fungal pathogens such as Candida glabrata. C. glabrata is found both in the environment and in diverse niches in its human host. The ambient pH of these niches varies considerably, and therefore we have examined the response of C. glabrata to changes in ambient pH using a proteomic approach. Proteins expressed in C. glabrata cells growing at pH 4.0, 7.4 or 8.0 were compared by 2-DE, and 174 spots displaying reproducible and statistically significant changes in expression level were identified by peptide mass fingerprinting, thereby extending our 2-DE map of the C. glabrata proteome to a total of 272 identified spots. Proteins involved in glucose metabolism, the TCA cycle, respiration and protein synthesis were expressed at lower levels during growth at pH 7.4 and/or 8.0, whereas proteins involved in stress responses and protein catabolism were expressed at higher levels under these alkaline conditions. Our data suggest that C. glabrata perceives low pH as less stressful than higher pH. This contrasts with another opportunistic fungal pathogen of humans, Candida albicans.