关键词： KPC-producing Klebsiella pneumoniae   MgrB   colistin resistance   virulence   bacterial persistence  

摘要： The global rise of carbapenem-resistant Klebsiella pneumoniae, including strains producing K. pneumoniae carbapenemase (KPC) types, poses a significant public health challenge due to their resistance to critical antibiotics. Treatment options for infections caused by KPC-producing K. pneumoniae (KPC-KP) are increasingly limited, particularly as these strains develop resistance to last-line antibiotics such as ceftazidime/avibactam and colistin. This study investigates the evolution of antibiotic resistance and persistence in a series of clonally related ST11 KPC-KP strains isolated from a single patient undergoing extended antimicrobial treatment. The patient, a 47-year-old male with a history of kidney transplantation, developed multiple KPC-KP lung infections during his hospital stay. Resistance to colistin and ceftazidime/avibactam emerged during treatment with these antibiotics. Key resistance mechanisms identified included the integration of ISKpn26 into mgrB gene, leading to mgrB inactivation and colistin resistance, and the emergence of novel bla(KPC-2) variants (bla(KPC-71) and bla(KPC-179)) that confer resistance to ceftazidime/avibactam. Despite the development of colistin resistance in a ceftazidime/avibactam-resistant KPC-KP strain following combination therapy, the patient's clinical condition significantly improved. Phenotypic assays showed that mgrB disruption in KPC-KP resulted in increased biofilm formation and higher susceptibility to phagocytosis. In mouse models, KPC-KP strains with mgrB disruption showed reduced virulence, increased lung colonization and persistence, and a lower inflammatory response, suggesting that mgrB disruption facilitates the transition from acute infection to colonization. This study highlights the complex interplay between antibiotic resistance and bacterial fitness, offering insights into why some patients experience clinical improvement despite severe drug resistance and incomplete bacterial clearance.

关键词： 企业“脱实向虚”   ESG评级   审计费用  

摘要： 本文基于2012-2022年中国上市公司数据，构建固定效应和调节效应模型，对企业“脱实向虚”、ESG评级和审计费用的关联效应和影响机制进行分析。研究发现，企业“脱实向虚”对审计费用存在正向影响，ESG评级会抑制企业“脱实向虚”对审计费用的正向作用，尤其是ESG三要素中的S（社会）、G（公司治理）调节效应更为突出。此外，在国有企业和第二、第三产业中，企业“脱实向虚”对审计费用的正向影响更为显著，同时在制造业，信息传输、软件和信息技术服务业和采矿业中，企业“脱实向虚”同样会显著提升审计费用。这些发现为理解企业“脱实向虚”与审计费用之间的影响关系提供新的视角。

关键词： Enterococcus faecium   vancomycin-resistant   multilocus sequence typing   pulsed-field gel electrophoresis   outbreak  

摘要： Vancomycin-resistant Enterococcus faecium (VREfm) is a major nosocomial pathogen, and molecular epidemiological tools are crucial for controlling its spread. Pulsed-field gel electrophoresis (PFGE) is still used in clinical laboratories despite the increased accessibility of whole-genome sequencing (WGS). As PFGE equipment is no longer commercially available, clinical laboratories need alternative tools. Highly standardized multilocus sequence typing (MLST) is one option. However, the original MLST scheme for E. faecium, designed in 2002, showed inconsistencies with WGS-based typing. Therefore, the new Bezdi & ccaron;ek MLST scheme, which offers more accurate genetic similarity based on genome-wide data, has recently been proposed. To clarify its clinical utility in analyzing nosocomial VREfm transmission, we compared both MLST schemes with PFGE using 68 VREfm isolates collected during an outbreak at a Japanese tertiary medical center in 2019. PFGE analysis identified nine clusters among the 68 strains, including two predominant clusters. The original scheme identified five sequence types (STOs), of which 82.4% (56/68) were STO192. The Bezdi & ccaron;ek scheme identified nine sequence types (STBs), subdividing the original STO192 into STB1162 (30/56), STB610 (25/56), and STB895 (1/56). Simpson's index of diversity values were 0.635, 0.317, and 0.648 for PFGE, the original scheme, and the Bezdi & ccaron;ek scheme, respectively. Combining the Bezdi & ccaron;ek scheme with admission records provided clearer outbreak visualization, indicating that two distinct STBs independently caused sequential outbreaks. With high discriminatory power comparable with PFGE and global availability, the Bezdi & ccaron;ek scheme is a practical and valuable tool for controlling nosocomial VREfm infections in clinical laboratories.

关键词： 全科医生   家庭医生签约   服务现状   服务质量   家庭医生团队   北京  

摘要： 背景家庭医生签约服务（家医服务）是我国深化医改的重要措施，旨在提升人民健康水平、卫生服务体系效率，家医服务在数量上已取得较快发展，但目前尚缺少家医服务质量相关的研究证据。目的 基于全科医生视角了解北京市家医服务质量现状和存在问题，为家医服务的质量改进提供参考依据。方法 2023年8月—2024年6月通过目的抽样选取来自北京市9个区18家社区卫生服务机构（机构）的18名全科医生，基于结构-过程-结果框架的访谈提纲对全科医生进行半结构访谈。通过主题分析法对资料进行分析并提炼访谈主题。结果 研究提炼出3个主题和11个子主题。主题一：家医服务的结构质量（政策引导及落实、机构的条件设施、家医服务的考核和激励机制、家医团队建设）。主题二：家医服务的过程质量（签约服务内容、转诊和就诊服务流程、出诊服务标准）。主题三：家医服务的效果（居民的健康水平提升、居民的就诊意愿增强、家医服务的居民认可度有待加强、全科医生的职业压力增加）。结论 自开展家医服务以来，服务质量逐步提升，但仍存在部分制约因素。应加强政策支持，优化服务内容及流程，将质量评价体系与激励机制相融合，提升全科医生的综合服务能力并建立高效的家医团队。