金黄色葡萄球菌耐药基因及新型抗菌药物的研究进展

金黄色葡萄球菌(Staphylococcus aureus,S.aureus),简称金葡菌,是一种临床常见致病菌,可引起皮肤化脓性感染、肺炎、心包炎、败血症及脓毒血症等多种疾病。目前临床上金黄色葡萄球菌的多重耐药情况已十分严峻,特别是耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)的出现,已成为临床抗感染治疗的棘手难题,严重危害人类健康。本文主要介绍金黄色葡萄球菌基因水平的耐药性、新型抗菌药物的研发及临床治疗金黄色葡萄球菌感染三方面的进展,为金黄色葡萄球菌的耐药性研究及耐药菌株的临床有效治疗提供科学依据。     

耐药机制指导下的抗金葡菌药物开发现状

金黄色葡萄球菌是全球院内感染的首要病原菌,临床分离的金葡菌80%以上为耐甲氧西林(MRSA)菌株,因其耐药性,尤其是多重耐药性的快速增长,抗MRSA感染日益成为抗感染治疗的难点和热点。近年来,人们在充分认识金葡菌耐药机制的基础上,积极开发新型抗MRSA药物,取得了长足发展。对MRSA的耐药机制及该机制指导下抗金葡菌药物开发现状作一综述。     

普通外科常见G+病原菌对抗生素耐药的分析

目的：研究普通外科感染的G^ 病原菌及其对常用抗生素的耐药性，以指导临床用药。方法：采用API—ATB System和Kirby—Bauer法，对外科临床标本进行细菌培养并检测其对多种抗生素的耐药性。结果：普通外科病房24个月共分离得到265株G^ 球菌，位列前3位的分别是金黄色葡萄球菌、表皮葡萄球菌、肠球菌。金葡菌对常用抗生素的耐药性较高，万古霉素仍是治疗G^ 球菌的有效药物。结论：监测G^ 球菌的耐药性，对指导外科临床抗生素的合理应用，提高外科抗感染疗效有重要意义。     

耐万古霉素的金黄色葡萄球菌

目前认为万古霉素中度耐药的金黄色葡萄球菌菌株一般从苯唑西林耐药的金黄色葡萄球菌转变而来。万古霉素中度耐药的金黄色葡萄球菌感染患者往往长期使用万古霉素或有慢性疾病。目前还没有系统检测万古霉素中度耐药的金黄色葡萄球菌的试验。如果用万古霉素治疗苯唑西林耐药的金黄色葡萄球菌感染失败,临床医生应警觉是否为万古霉素中度耐药的金黄色葡萄球菌感染。     

深圳市人民医院近五年临床分离金黄色葡萄球菌的 分布及耐药性分析

目的分析医院感染患者金黄色葡萄球菌的临床分布特征及耐药性变化,为临床治疗金黄色葡萄球菌感染提供依据。方法回顾性分析2012年1月至2016年12月我院从临床各类标本中分离获得的1 141株金黄色葡萄球菌,统计其在各类标本和病区中的分布特点,并用K-B法测定该菌对常用抗菌药物的敏感性。结果 5年中共分离出1 141株金黄色葡萄球菌,标本来源构成比最多的是伤口分泌物(43.3%)、呼吸道标本(24.0%)和血液标本(10.2%)。耐甲氧西林金黄色葡萄球菌(MRSA)共有339株,占29.7%。各年MRSA的检出数依次为53株(31.9%)、51株(26.0%)、82株(35.2%)、81株(30.3%)和72株(26.0%)。MRSA主要分离自神经外科(13.8%)、呼吸监护室(10.6%)、重症监护室(8.8%)和骨科(7.7%)。MRSA对抗菌药物的耐药性普遍高于MSSA,二者比较差异有统计学意义(P0.05)。未发现对万古霉素、利奈唑胺、替考拉宁耐药的金黄色葡萄球菌。结论 MRSA感染多发生于长期使用抗菌药物,有皮肤软组织伤口及侵入性操作的科室及患者。MRSA具有多重耐药性,应严格掌握抗菌药物的使用适应证;同时临床治疗应根据药物敏感性报告针对性地合理用药,以便及时有效地控制感染并防止耐药菌株的扩散。     

耐甲氧西林金黄色葡萄球菌的耐药及其检测方法

耐甲氧西林金黄色葡萄球菌（MRSA）是引起医院感染的多重耐药菌,其有效的治疗药物为万古霉素。近年已发现对万古霉素耐受的金黄色葡萄球菌,金黄色葡萄球菌一旦对万古霉素耐药,临床将面临无药可供选择的局面。由于其所造成治疗上的困难,对其耐药机制的深入研究和该菌准确、及时的检出对于寻找新的治疗靶位和防止其播散有着极其重要的意义。本文就mecA耐药决定子、调节基因、染色体上的辅助基因对耐甲氧西林金黄色葡萄球菌耐药表达的影响及其表型和基因检测方法作一综述。     

NICU与综合性ICU感染金黄色葡萄球菌的耐药性对比分析

目的比较新生儿重症监护病房(NICU)与综合性重症监护病房(ICU)金黄色葡萄球菌的耐药性,为临床合理选用抗菌药物提供依据。方法对2011年6月—2015年7月NICU与综合性ICU患者临床标本中分离的金黄色葡萄球菌278株的耐药性比较,药敏试验采用纸片扩散法,采用WHONET5.6和SPSS 20.0软件进行数据分析。结果 278株金黄色葡萄球菌对青霉素G、氨苄西林、美洛西林、头孢西丁等大部分抗菌药物的耐药率已较高,分别为100.00%、93.88%、80.94%、51.08%;综合性ICU感染金黄色葡萄球菌对克拉霉素、万古霉素、利奈唑胺、呋喃妥因等耐药率较低,分别为7.81%、0.00%、0.00%、0.00%;NICU与综合性ICU病房耐甲氧西林金黄色葡萄球菌(MRSA)检出率分别为34.88%和51.04%,NICU病房MRSA检出率低于ICU(P0.05);头孢唑林及头孢噻肟在NICU与综合性ICU病房中的耐药率分别为19.77%,33.33%;13.95%,40.10%;NICU分离出的金黄色葡萄球菌对头孢唑林和头孢噻肟耐药率低于综合性ICUU,差异有统计学意义(P0.05);万古霉素及呋喃妥因在NICU与综合性ICU金黄色葡萄球菌中的耐药率分别为2.33%,0.00%;0.00%,0.00%;耐药率均较低(P0.05)。结论临床选用抗菌药物应根据不同病区感染病原菌的耐药性和患者不同生理特点,本地区治疗NICU金黄色葡萄球菌感染可选头孢唑林和头孢噻肟,综合性ICU可选利奈唑胺和克拉霉素作为首选药。     

重症监护病房金黄色葡萄球菌耐药性与流行病学分析

为了解重症监护病房感染金黄色葡萄球菌的耐药性及流行状况,收集重症监护病房2007年9～12月临床分离的金黄色萄萄球菌42株,纸片扩散法检测其对10种抗生素的耐药率,随机引物扩增PCR(Ran- dom amplified polymorphic DNA,RAPD)检测其流行状况。42株金黄色葡萄球菌对氨苄西林的耐药率最高,没有检测到对万古霉素耐药的金黄色葡萄球菌。35株金黄色葡萄球菌为耐甲氧西林的金黄色葡萄球菌(MR- SA),7株为甲氧西林敏感的葡萄球菌(MSSA),除万古霉素外,MRSA对其他9种抗生素的耐药率比MSSA高,42株金黄色葡萄球菌经RAPD分型分为5个基因型,其中Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ型分别占31.0%、38.1%、14.3%、9.5%、7.1%。重症监护病房临床金黄色葡萄球菌分离株对多种抗生素具有高耐药性,其感染基因型以Ⅰ、Ⅱ型为主。     

对万古霉素敏感性下降的金黄色葡萄球菌研究进展

随着MRSA的越发,万古霉素在临床上的使用越来越频繁,成为治疗MRSA的最后一道防线;然而,对万古霉素敏感性下降的金黄色葡萄球菌的出现,临床上抗感染治疗面临极大困难,引起了医学界普遍的关注。本文对万古霉素敏感性下降的金黄色葡萄球菌的发展,耐药状况,作用机制,相关治疗和热门争议话题等方面的研究进展作一综述。     

对万古霉素敏感性下降的金黄色葡萄球菌研究进展

随着MRSA的越发,万古霉素在临床上的使用越来越频繁,成为治疗MRSA的最后一道防线;然而,对万古霉素敏感性下降的金黄色葡萄球菌的出现,临床上抗感染治疗面临极大困难,引起了医学界普遍的关注。本文对万古霉素敏感性下降的金黄色葡萄球菌的发展,耐药状况,作用机制,相关治疗和热门争议话题等方面的研究进展作一综述。     

7,10-Epoxyoctadeca-7,9-dienoic Acid: A Small Molecule Adjuvant That Potentiates β-Lactam Antibiotics Against Multidrug-Resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) infections with multi-drug resistance needs effective and alternative control strategies. In this study we investigated the adjuvant effect of a novel furan fatty acid, 7,10-epoxyoctadeca-7,9-dienoic acid (7,10-EODA) against multidrug-resistant S. aureus (MDRSA) strain 01ST001 by disc diffusion, checker board and time kill assays. Further the membrane targeting action of 7,10-EODA was investigated by spectroscopic and confocal microscopic studies. 7,10-EODA exerted synergistic activity along with β-lactam antibiotics against all clinical MRSA strains, with a mean fractional inhibitory concentration index below 0.5. In time-kill kinetic study, combination of 7,10-EODA with oxacillin, ampicillin, and penicillin resulted in 3.8–4.2 log₁₀ reduction in the viable counts of MDRSA 01ST001. Further, 7,10-EODA dose dependently altered the membrane integrity (p < 0.001) and increased the binding of fluorescent analog of penicillin, Bocillin-FL to the MDRSA cells. The membrane action of 7,10-EODA further facilitated the uptake of several other antibiotics in MDRSA. The results of the present study suggested that 7,10-EODA could be a novel antibiotic adjuvant, especially useful in repurposing β-lactam antibiotics against multidrug-resistant MRSA.     

EV71 infection correlates with viral IgG preexisting at pharyngolaryngeal mucosa in children

Enterovirus 71(EV71) infection causes severe central nervous system damage, particularly for children under the age of 5 years old, which remains a major public health burden worldwide. Clinical data released that children may be repeatedly infected by different members in enterovirus and get even worsen. Mucosa, especially epithelium of alimentary canal, was considered the primary site of EV71 infection. It has been elusive whether the preexsiting viral antibody in mucosa plays a role in EV71 infection. To answer this question, we respectively measured viral antibody response and EV71 RNA copy number of one hundred throat swab specimens from clinically confirmed EV71-infected children. The results released that low-level of mucosal Ig G antibody against EV71 broadly existed in young population. More importantly, it further elucidated that the children with mucosal preexsiting EV71 Ig G were prone to be infected, which suggested a former viral Ig G mediated enhancement of viral infection in vivo.     

Leptotrichia species in human infections

Leptotrichia species typically colonize the oral cavity and genitourinary tract. These anaerobic bacteria belong to the normal flora of humans and are seldom found in clinically significant specimens. However, on rare occasions, Leptotrichia has been isolated from blood cultures of patients with lesions in the oral mucosa, in particular from patients with neutropenia. These organisms should be considered potential pathogens in neutropenic patients, especially when breaks in the mucosal barriers are present through which they frequently spread to the bloodstream. Leptotrichia has also been recovered from immunocompetent persons, e.g. patients with endocarditis. Although their role in infections remains elusive and not much is known, they have been suggested as emerging pathogens. The present review deals with taxonomy, diagnosis, clinical importance, pathogenesis, host defence, infection control, and spectrum of Leptotrichia infections, and ends with a few typical case reports. Currently, six species have been validly published, but a number of yet uncultivable species exist. Molecular methods recovering uncultivable species should be used to get a real idea of their role as pathogens.     

Breakthrough Disseminated Scedosporium prolificans Infection in a Patient with Relapsed Leukaemia on Prolonged Voriconazole Followed by Posaconazole Prophylaxis

A man with acute lymphoblastic leukaemia developed disseminated Scedosporium prolificans infection following chemotherapy for disease relapse while on posaconazole prophylaxis. Scedosporium prolificans infection during posaconazole prophylaxis has not been reported previously. This report is timely as the uptake of posaconazole, the broadest spectrum azole clinically available, is likely to grow with recent evidence supporting its role as prophylaxis against invasive fungal infections in high-risk haematology patients.     

Histopathologic criterion of dysplasia of the uterine cervix and its biological nature.

A histopathologic diagnostic standard for abnormal epithelium of the uterine cervix, based on its biological behavior, has been proposed, and dysplasia and carcinoma in situ have been classified according to this standard. Benign dysplasia by this classification may be considered as a benign lesion, and only the lesion which satisfies the standard for atypical dysplasia should be considered as dysplasia, having a significance as a precursor to cervical cancer. This would be clinically convenient.     

Studies of the effect of acemannan on retrovirus infections: clinical stabilization of feline leukemia virus-infected cats.

Feline leukemia is a disease induced by an oncornavirus infection that inevitably causes clinically affected cats to die. It has been estimated that 40% of cats are dead within 4 weeks and 70% within 8 weeks of the onset of clinical symptoms. Acemannan is a complex carbohydrate with both immunostimulatory and direct antiviral properties. Administration of acemannan for 6 weeks intraperitoneally to clinically symptomatic cats significantly improved both the quality of life and the survival rate. Twelve weeks after initiation of treatment, 71% of treated cats were alive and in good health.     

Uncovering Symptom Progression History from Disease Registry Data with Application to Young Cystic Fibrosis Patients

Summary The growing availability of various disease registry data has brought precious opportunities to epidemiologists to understand the natural history of the registered diseases. It also presents challenges to the traditional data analysis techniques because of complicated censoring/truncation schemes and temporal dynamics of covariate influences. In a case study of the Cystic Fibrosis Foundation Patient Registry data, we propose analyses of progressive symptoms using temporal process regressions, as an alternative to the commonly employed proportional hazards models. Two endpoints are considered, the prevalence of ever positive and currently positive for Pseudomonas aeruginosa (PA) infection in the lungs, which capture different aspect of the disease process. The analysis of ever PA positive via a time‐varying coefficient model demonstrates the lack of fit, as well as the potential loss of information, in the standard proportional hazards analysis. The analysis of currently PA positive yields results that are clinically meaningful and have not previously been reported in the cystic fibrosis literature. Our analyses demonstrate that prenatal/neonatal screening results in lower prevalence of PA infection compared to traditional diagnosis via signs and symptoms, but this benefit attenuates with age. Calendar years of diagnosis also affect the risk of PA infection; patients diagnosed in more recent cohort show higher prevalence of ever PA positive but lower prevalence of currently PA positive.     

Importance of secretory antibodies in nonsusceptibility to influenza B disease and the prevention of the spread of this virus

Under the conditions of the natural outbreak of influenza B a rise in the level of antibodies in the blood serum and respiratory tract secretions has been found to occur in nonimmunized persons during this disease. Secretory antibodies, along with serum antibodies and in interaction with them, prevent the development of clinically manifest influenza. The asymptomatic form of influenza infection has been revealed: during this form of the disease the response of the body is limited to the local immunity system.     

Study of immunological mechanisms of action of temperature and emotional stress factors in experimental flavivirus infections

The influence of two stress factors, sharp changes in temperature and hypokinesia, on the course of experimental tick-borne encephalitis and Langat virus infections in mice has been studied. The data obtained in this study indicate that both factors produce defects in T- and B-cell-mediated immunity, accompanied by the activation of asymptomatic infection and the decrease of the mean survival time in acute infection. These two stress factors, differing in their intensity and nature (physical and emotional), have been shown to produce the same effect on the course of acute and asymptomatic flavivirus infections. In the former case the mean survival time of the animals decreases, and in the latter case clinically manifest infection develops. Under the conditions of hypokinesia (or changes in temperature), the death rate among the animals infected with langat virus has been found to increase 3- to 4-fold in comparison with the controls, the mortality level in the groups subjected to different stress factors being the same.     

DRY-ROT DISEASE OF THE POTATO

A study has been made of the incidence of dry rot in seed potatoes in relation to commercial handling methods, and it has been shown that infection following grading by mechanical reciprocating riddles fitted with bare wire screens is more serious than that following normal handling at harvest or during transport. Hand picking, hand riddling and the use of rubber-spool graders or rubber-coated screens reduced infection by varying amounts. The higher incidence of the disease in 'transported' as against 'home-saved' seed is regarded as being due to machine grading of such stocks some months prior to planting.
Contamination of stores or boxes has not been found to play any material part in the spread of infection under commercial conditions unless tubers are roughly handled during storage. As contact infection has been found to be rare, it is considered that the practice of 'picking over' stocks during the winter to remove diseased tubers is unnecessary and may lead to further infection.
In addition to wounds, lesions of both blight and powdery scab, but not common scab, have been found to be a means of infection.