包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺...包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺类药物的机制尚未明确。已有研究提示,GAS体内耐受β-内酰胺类药物与菌株对药物的敏感性降低、细菌的接种效应、生物膜的形成、共存菌的作用、细菌持留性及细菌可内化入胞内等因素有关。该文回顾总结了β-内酰胺类药物临床治疗GAS感染失败的主要报道,以及与GAS体内耐受β-内酰胺类药物机制相关的重要研究,为后续研究及临床用药提供参考。展开更多
目的分析总结A组乙型溶血性链球菌(group A Streptococcus pyogens,GAS)感染患者的临床特点以提高诊疗水平。方法收集温州医科大学附属第二医院自2005-2016年收住的90例证实为GAS感染患者的临床资料并进行统计分析。结果GAS感染在儿童...目的分析总结A组乙型溶血性链球菌(group A Streptococcus pyogens,GAS)感染患者的临床特点以提高诊疗水平。方法收集温州医科大学附属第二医院自2005-2016年收住的90例证实为GAS感染患者的临床资料并进行统计分析。结果GAS感染在儿童中最常见的疾病表现为扁桃体炎(38.0%),成人中则为局部皮肤软组织感染(72.7%)。实验室指标,C反应蛋白(CRP)、白细胞(WBC)、降钙素原(PCT)、抗链球菌溶血素O(ASO)可有所升高。目前GAS对常用抗菌药物仍较敏感。预后89例治愈后出院,1例死亡病例。结论GAS感染在儿童中以学龄期常见,在成人中以中年期常见。GAS感染患者在合理使用抗菌药物后,预后良好,少有危重症感染发生。展开更多
Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus(GAS)is a public health priority.The species defining group A cell wall carbohydrate(GAC,Lancefield antigen)can be ...Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus(GAS)is a public health priority.The species defining group A cell wall carbohydrate(GAC,Lancefield antigen)can be engineered to remove its immunodominant N-acetylglucosamine(GlcNAc)side chain,implicated in provoking autoimmune cross-reactivity in rheumatic heart disease,leaving its polyrhamnose core(GACPR).Here we generate a novel protein conjugate of the GACPR and test the utility of this conjugate antigen in active immunization.Instead of conjugation to a standard carrier protein,we selected SpyAD,a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen.SpyAD was synthesized using the XpressTM cell-free protein expression system,incorporating a non-natural amino acid to which GACpr was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GACPR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes.The conjugated SpyAD-GACPR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils.Active immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR,together with candidate vaccine antigens streptolysin O and C5a peptidase,protected against GAS challenge in a systemic infection model and localized skin infection model,without evidence of cross reactivity to human heart or brain tissue epitopes.This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.展开更多
A组链球菌（group A Streptococcus，GAS）或酿脓链球菌（Streptococcus pyogenes）能引起多种疾病，包括猩红热、毒素休克样综合征、风湿热、咽炎及急性肾小球肾炎等。随着抗生素的广泛使用，在发达国家和地区GAS引起的重症感染其发病...A组链球菌（group A Streptococcus，GAS）或酿脓链球菌（Streptococcus pyogenes）能引起多种疾病，包括猩红热、毒素休克样综合征、风湿热、咽炎及急性肾小球肾炎等。随着抗生素的广泛使用，在发达国家和地区GAS引起的重症感染其发病率曾明显下降，但20世纪80年代中后期，欧美各国也包括发展中国家相继报道风湿热的局部暴发以及侵袭性感染的发病率显著上升，使得GAS感染再次受到高度重视。展开更多
Importance:The use of the rapid antigen-detection test(RADT)has become the standard of care in the early diagnosis of group A beta-hemolytic Streptococcus(GAS)pharyngitis.Concern has been expressed over increased fals...Importance:The use of the rapid antigen-detection test(RADT)has become the standard of care in the early diagnosis of group A beta-hemolytic Streptococcus(GAS)pharyngitis.Concern has been expressed over increased false positives when the child had been treated recently for GAS pharyngitis,resulting in over use of antibiotics.Objective:To determine if the false positive rate for RADT is increased in children recently treated for GAS pharyngitis.Methods:We conducted a prospective study to evaluate 300 children from a private practice with acute pharyngitis who were treated for GAS pharyngitis within the preceding 28 days(study group)compared to 306 children of comparable age who had not been previously treated(control group).RADT and throat culture were performed on all children presenting with signs and symptoms of acute pharyngitis.The false positive and false negative rates were determined and compared in both groups.results:The false positive rate of 11.5%(23/200)in the study group was significantly higher than the false positive rate of 0 in the control group.False positives were more likely to occur in younger children.Interpretation:These data would indicate that while RADT is reliable in most children,it can lead to over treatment in children who have been recently treated for GAS.In children treated in the preceding 28 days for GAS pharyngitis,the presence of infection should be determined with a throat culture only.Treatment based on a positive RADT should be reserved for children not recently treated for GAS pharyngitis.展开更多
文摘包括青霉素在内的β-内酰胺类药物用于治疗A族链球菌(group A Streptococcus,GAS)感染已有80余年,虽然体外试验尚未发现对其耐药的GAS菌株,但自20世纪50年代以来,时有β-内酰胺类药物临床治疗GAS感染失败的报道。GAS体内耐受β-内酰胺类药物的机制尚未明确。已有研究提示,GAS体内耐受β-内酰胺类药物与菌株对药物的敏感性降低、细菌的接种效应、生物膜的形成、共存菌的作用、细菌持留性及细菌可内化入胞内等因素有关。该文回顾总结了β-内酰胺类药物临床治疗GAS感染失败的主要报道,以及与GAS体内耐受β-内酰胺类药物机制相关的重要研究,为后续研究及临床用药提供参考。
文摘目的分析总结A组乙型溶血性链球菌(group A Streptococcus pyogens,GAS)感染患者的临床特点以提高诊疗水平。方法收集温州医科大学附属第二医院自2005-2016年收住的90例证实为GAS感染患者的临床资料并进行统计分析。结果GAS感染在儿童中最常见的疾病表现为扁桃体炎(38.0%),成人中则为局部皮肤软组织感染(72.7%)。实验室指标,C反应蛋白(CRP)、白细胞(WBC)、降钙素原(PCT)、抗链球菌溶血素O(ASO)可有所升高。目前GAS对常用抗菌药物仍较敏感。预后89例治愈后出院,1例死亡病例。结论GAS感染在儿童中以学龄期常见,在成人中以中年期常见。GAS感染患者在合理使用抗菌药物后,预后良好,少有危重症感染发生。
基金supported by the CARB-X,Vaxcyte,Inc.,and NIH Grant(AI077780)NJG was supported in part by a Ruth L.Kirschstein Institutional National Research Award from the National Institute for General Medical Sciences(T32 GM008666)。
文摘Development of an effective vaccine against the leading human bacterial pathogen group A Streptococcus(GAS)is a public health priority.The species defining group A cell wall carbohydrate(GAC,Lancefield antigen)can be engineered to remove its immunodominant N-acetylglucosamine(GlcNAc)side chain,implicated in provoking autoimmune cross-reactivity in rheumatic heart disease,leaving its polyrhamnose core(GACPR).Here we generate a novel protein conjugate of the GACPR and test the utility of this conjugate antigen in active immunization.Instead of conjugation to a standard carrier protein,we selected SpyAD,a highly conserved GAS surface protein containing both B-cell and T-cell epitopes relevant to the bacterium that itself shows promise as a vaccine antigen.SpyAD was synthesized using the XpressTM cell-free protein expression system,incorporating a non-natural amino acid to which GACpr was conjugated by site-specific click chemistry to yield high molecular mass SpyAD-GACPR conjugates and avoid disruption of important T-cell and B-cell immunological epitopes.The conjugated SpyAD-GACPR elicited antibodies that bound the surface of multiple GAS strains of diverse M types and promoted opsonophagocytic killing by human neutrophils.Active immunization of mice with a multivalent vaccine consisting of SpyAD-GACPR,together with candidate vaccine antigens streptolysin O and C5a peptidase,protected against GAS challenge in a systemic infection model and localized skin infection model,without evidence of cross reactivity to human heart or brain tissue epitopes.This general approach may allow GAC to be safely and effectively included in future GAS subunit vaccine formulations with the goal of broad protection without autoreactivity.
文摘A组链球菌（group A Streptococcus，GAS）或酿脓链球菌（Streptococcus pyogenes）能引起多种疾病，包括猩红热、毒素休克样综合征、风湿热、咽炎及急性肾小球肾炎等。随着抗生素的广泛使用，在发达国家和地区GAS引起的重症感染其发病率曾明显下降，但20世纪80年代中后期，欧美各国也包括发展中国家相继报道风湿热的局部暴发以及侵袭性感染的发病率显著上升，使得GAS感染再次受到高度重视。
文摘Importance:The use of the rapid antigen-detection test(RADT)has become the standard of care in the early diagnosis of group A beta-hemolytic Streptococcus(GAS)pharyngitis.Concern has been expressed over increased false positives when the child had been treated recently for GAS pharyngitis,resulting in over use of antibiotics.Objective:To determine if the false positive rate for RADT is increased in children recently treated for GAS pharyngitis.Methods:We conducted a prospective study to evaluate 300 children from a private practice with acute pharyngitis who were treated for GAS pharyngitis within the preceding 28 days(study group)compared to 306 children of comparable age who had not been previously treated(control group).RADT and throat culture were performed on all children presenting with signs and symptoms of acute pharyngitis.The false positive and false negative rates were determined and compared in both groups.results:The false positive rate of 11.5%(23/200)in the study group was significantly higher than the false positive rate of 0 in the control group.False positives were more likely to occur in younger children.Interpretation:These data would indicate that while RADT is reliable in most children,it can lead to over treatment in children who have been recently treated for GAS.In children treated in the preceding 28 days for GAS pharyngitis,the presence of infection should be determined with a throat culture only.Treatment based on a positive RADT should be reserved for children not recently treated for GAS pharyngitis.
