长春市金葡菌耐药状况及耐甲氧西林金葡菌基因分型

目的调查长春地区临床分离金葡菌的耐药状况及Panton—Valentine杀白细胞素（PVL）分布情况；确定耐甲氧西林金葡菌（MRSA）染色体及葡萄球菌me~盒式染色体（SCCmec）基因分型。方法琼脂稀释法测定苯唑西林等17种抗菌药物对2004年6月～2005年1月长春市3家教学医院临床标本分离的83株金葡菌的最低抑菌浓度（MIC）；聚合酶链式反应（PCR）进行金葡菌的PVL基因检测；脉冲场凝胶电泳（PFGE）对MRSA菌株作染色体同源性分析。多重PCR方法检测MRSA的SCCmec基因分型。结果83株金葡菌中MRSA12株（占14．5％）；金葡菌PVL的基因阳性7株（占8．4％）。MRSA对β-内酰胺类、红霉素、克林霉素、庆大霉素、四环素、氟喹诺酮类耐药率均超过90％，对氯霉素、利福平耐药率分别为8．3％、58．3％。未发现对糖肽类及复方磺胺甲嗯唑耐药的MRSA。甲氧西林敏感金葡菌（MSSA）对青霉素G、红霉素、克林霉素、四环素、庆大霉素耐药率分别为95．8％、67．6％、49．3％、45．1％、26．8％，对头孢菌素、氯霉素、利福平、氟喹诺酮类、复方磺胺甲曙唑耐药率均低于20％。MRSA的PFGE显示为A、B两种类型，以A型为主，占92％（11／12），三家医院均有分布。MRSA的SCCmec分型．Ⅲ型为主75％（9／12）。结论长春市MRSA发生率低于国内报道平均水平；MRSA为两种不同类型克隆株，在不同医院间存在克隆传播；未发现社区获得性MRSA菌株。     

The potential use of toxin antibodies as a strategy for controlling acute Staphylococcus aureus infections

INTRODUCTION: The pandemic human pathogen, Staphylococcus aureus, displays high levels of antibiotic resistance and is a major cause of hospital- and community-associated infections. S. aureus disease manifestation is to a great extent due to the production of a large arsenal of virulence factors, which include a series of secreted toxins. Antibodies to S. aureus toxins are found in people who are infected or asymptomatically colonized with S. aureus. Immunotherapies consisting of neutralizing anti-toxin antibodies could provide immediate aid to patients with impaired immune systems or in advanced stages of disease. AREAS COVERED: Important S. aureus toxins, their roles in pathogenesis, rationales for selecting S. aureus toxins for immunization efforts, and caveats associated with monoclonal antibody-based passive immunization are discussed. This review will focus on hyper-virulent community-associated methicillin-resistant S. aureus because of their recent surge and clinical importance. EXPERT OPINION: Antibodies against genome-encoded toxins may be more broadly applicable than those directed against toxins found only in a sub-population of S. aureus isolates. Furthermore, there is substantial functional redundancy among S. aureus toxins. Thus, an optimal anti-S. aureus formulation may consist of multiple antibodies directed against a series of key S. aureus genome-encoded toxins.     

Use of daptomycin for treatment of Staphylococcus aureus infections

Gram-positive bacteria such as Staphylococcus aureus are important human pathogens. An increasing proportion of S. aureus are methicillin resistant. For decades, methicillin-resistant S. aureus infections have been treated with vancomycin, but susceptibility is decreasing, and tissue penetration and safety profile (especially nephrotoxicity) is not ideal. Consequently, there is a great need for the development of antibiotics with demonstrated efficacy and safety for infections caused by S. aureus and other Gram-positive pathogens. One such antibiotic is daptomycin, which has a unique mechanism of action and potent, rapid bactericidal activity, without causing cell lysis. Daptomycin has demonstrated significant efficacy in the treatment of complicated skin and skin structure infections, as well as methicillin-susceptible and methicillin-resistant S. aureus bacteremia, including right-sided endocarditis. Other attributes include an excellent safety profile, low potential for resistance, and once-daily dosing.     

Immunotherapeutics for nosocomial infections

Nosocomial or hospital-acquired infections are associated with prolonged hospitalisation and increased healthcare costs and resource utilisation. Continued advances in sophisticated medical procedures, an increase in the number of immunocompromised patients and a steady rise in the prevalence of antibiotic-resistant organisms has renewed interest in the development of novel therapies that can treat nosocomial infections. This review focuses on novel immunological approaches to address this significant unmet medical need.     

Nadifloxacin: a quinolone for topical treatment of skin infections and potential for systemic use of its active isomer,WCK 771

Nadifloxacin is a potent, broad-spectrum, quinolone agent approved for topical use in acne vulgaris and skin infections in Japan. As exposure of pathogenic and colonising bacteria to antibiotics results in drug resistance, it is not desirable to use an important, broad-spectrum antibiotic, which belongs to a class of agents widely used systemically to treat a wide variety of infections, as a topically applied preparation. On this basis, nadifloxacin is not a good option for topical treatment of acne when other effective non-antibiotic treatments are available. Nadifloxacin has potential as a topical agent for short-term treatment of skin infections. The arginine salt of its (-)-(S)-isomer is being developed as a parenteral agent based on its potency against methicillin and quinolone-resistant Staphylococcus aureus.     

金黄色葡萄球菌肠毒素B功能表位及中和抗体研究进展

金黄色葡萄球菌(金葡菌)肠毒素B(SEB),是造成食物中毒乃至中毒性休克综合征的主要病因。SEB也是一种超级抗原,可以刺激T细胞,能够同时与抗原呈递细胞上的主要组织相容性复合物Ⅱ类分子和T细胞受体上的Vβ结合。随着SEB的结构逐步得到解析,揭示了SEB结构与功能的关键表位。临床上尚无针对SEB中毒的有效疫苗和药物。SEB中和抗体因其高特异性和低毒副作用,成为研究者们的研究首选和重点,从鼠源抗体、人鼠嵌合抗体到人源抗体等均有报道。本文对SEB功能表位及其中和抗体的研究进展进行综述。     

利奈唑胺治疗老年人院内耐甲氧西林金黄色葡萄球菌感染的效果分析

目的 探讨利奈唑胺治疗老年人院内耐甲氧西林金黄色葡萄球菌感染的效果.方法 90例老年耐甲氧西林金黄色葡萄球菌感染者根据治疗方法的不同分为治疗组与对照组,各45例,治疗组给予利奈唑胺治疗,对照组给予万古霉素治疗.结果 两组都无死亡患者,治疗组的总有效率为91.1％,对照组总有效率为75.6％,组间差异有统计学意义（P＜0.05）;两组不良反应发生率差异也有统计学意义（P＜0.05）.结论 利奈唑胺治疗老年人院内耐甲氧西林金黄色葡萄球菌感染效果明显优于万古霉素,且安全性更好,有很好的推广价值.     

Extremely Low Excretion of Daptomycin into Breast Milk of a Nursing Mother with Methicillin-Resistant Staphylococcus aureus Pelvic Inflammatory Disease

Antibiotic treatment for pelvic inflammatory disease (PID) is often broad spectrum and targets a diverse range of vaginal flora. Treatment of PID in nursing mothers presents a particular clinical challenge because use of antimicrobials during breastfeeding poses several potential risks to infants. Excretion of drugs into breast milk can occur through different mechanisms and depends on the characteristics of both the drug and the mother. Whether daptomycin is excreted into breast milk is unknown, as is its subsequent exposure to breastfeeding infants and the associated risks. We describe a case of PID caused by methicillin-resistant Staphylococcus aureus, an uncommon pathogen in PID, in a breastfeeding mother who was successfully treated with daptomycin. Daptomycin concentrations in her breast milk were measured to determine potential exposure to her infant. These concentrations were extremely low, with an estimated milk:plasma ratio of 0.0012. Although additional confirmatory studies are needed, daptomycin may be a reasonable option in the treatment of PID caused by gram-positive organisms that are resistant to other antibiotics.     

Agonistic antibodies to human glucocorticoid-induced tumor necrosis factor receptor as potential stimulators of T cell immunity for the treatment of cancer and viral infections

The magnitude of adaptive T cell responses is controlled by costimulatory molecules, including cell-surface associated members of the tumor necrosis factor receptor (TNF-R) family that modulate T cell receptor (TCR)-dependent activation, and by a network of regulatory T (Treg) cells that downregulate effector T cell functions. The glucocorticoid-induced TNF-R (GITR) is a type I transmembrane protein that is expressed at high levels on CD4⁺ CD25⁺ Treg cells and on activated effector T cells. In vitro studies have shown that ligation of GITR with an agonistic monoclonal antibody (mAb) could abrogate the suppressive activity of Treg cells and enhance the survival, proliferation and effector functions of TCR-activated CD4⁺ and CD8⁺ T cells. Furthermore, studies in mice demonstrated that mAb-triggered GITR stimulation could also markedly augment antitumor and virus-specific T cell responses in vivo. This has suggested that agonistic anti-GITR mAbs may serve to stimulate T cell immunity for therapeutic purposes. Accordingly, the present patent application reports the generation of a novel agonistic murine mAb to human GITR that is able to reverse Treg-mediated suppression and costimulate T cell activation in vitro. Humanized versions of the mAb are also described, but without providing data on their binding and functional properties. Further studies will be needed to fully appraise the potential utility of these human mAbs for the immunotherapy of cancer or viral infections.     

In-Host Emergence of Linezolid Resistance in a Complex Pattern of Toxic Shock Syndrome Toxin-1-Positive Methicillin-Resistant Staphylococcus aureus Colonization in Siblings with Cystic Fibrosis

Methicillin-resistant Staphylococcus aureus (MRSA) can cause chronic lung infections in patients with Cystic Fibrosis (CF). One option for managing them is the use of linezolid. We hereby report the in-host emergence of linezolid resistance (LR) in MRSA in CF siblings via a population analysis. A collection of 171 MRSA strains from 68 samples were characterized by determining their linezolid Minimal Inhibitory Concentrations (MICs), analyzing the locus of staphylococcal protein A (spa) and whole genome sequencing. Courses of linezolid were retraced. Strains belonged to three spa types (t002, t045, t127) and two sequence types (ST1, ST5). Emergence of LR occurred under treatment, one year apart in both siblings, in the CC5-MRSA-I Geraldine clone harboring the toxic shock syndrome toxin-1-encoding gene. Resistance was related to a G2576T substitution present in a variable number of 23S rRNA gene copies. Susceptible and resistant strains were co-isolated within samples. Single Nucleotide Polymorphism-based analysis revealed complex colonizations by highly diversified, clonally related populations. LR remains rare in MRSA and there are very few longitudinal analyses documenting its emergence. Analyzing a large MRSA collection revealed new aspects of LR emergence: it emerges in specific subclonal lineages resulting from adaptive diversification of MRSA in the CF lung and this heterogeneity of intra-sample resistance may contribute to compromising antibiotic management.