The rapid in situ inhibition of bacterial contamination and subsequent infection without inducing drug resistance is highly vital for the successful implantation and long-term service of titanium(Ti)-based orthopedic ...The rapid in situ inhibition of bacterial contamination and subsequent infection without inducing drug resistance is highly vital for the successful implantation and long-term service of titanium(Ti)-based orthopedic implants.However,the instability and potential cytotoxicity of current coatings have deterred their clinical practice.In this study,anodic oxidized titania nanotubes(TNT)were modified with antibacterial polyhexamethylene guanidine(PG)with the assistance of 3,4-dihydroxyphenylacetic acid.Interestingly,the prepared TNT-PG coating exhibited superior in vitro antibacterial activity than flat Ti-PG coating and effectively killed typical pathogens such as Escherichia coli and superbug methicillinresistant Staphylococcus aureus with above 4-log reduction(>99.99%killed)in only 5 min.TNT-PG coating also exerted excellent hemocompatibility with red blood cells and nontoxicity toward mouse pre-osteoblasts(MC3 T3-E1)in 1 week of coculture.In addition,the efficient in vivo anti-infective property of this coating was observed in a rat subcutaneous infection model.More importantly,TNT-PG coating improved the expression of alkaline phosphatase and enhanced the extracellular matrix mineralization of pre-osteoblasts,denoting its osteoinductive capacity.This versatile TNT-PG coating with excellent antibacterial activity and biocompatibility could be a promising candidate for advanced orthopedic implant applications.展开更多
Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with ...Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.Methods:We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024.Data on demographics,clinical features,microbiology,treatment,and outcomes were collected.Results:A total of 1,783 infection episodes were recorded,including 1,668 first infections and 115 second infections.Most infections were community-acquired(86.6%).Pneumonia was the most common infection type(26.7%),followed by spontaneous bacterial peritonitis(19.5%)and spontaneous bacteremia(14.1%).Among 754 pathogens isolated from 620 patients,Klebsiella pneumoniae(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of all isolates,with extended-spectrum p-lactamase-producing Escherichia coli being the most prevalent MDR strain(8.9%of patients).Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study(21.5%vs.61.2%,P<0.001),accompanied by a lower clinical resolution rate(63.5%vs.79.8%,P<0.001).Conclusions:The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions.These findings highlight the need for region-specific management and prevention strategies,particularly in light of the changing microbiological landscape,high MDR prevalence,and suboptimal antibiotic practices.展开更多
Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections ...Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.展开更多
基金the National Key R&D Program of China(No.2018YFC1105402)the National Natural Science Foundation of China(No.21875189)+1 种基金the Key R&D Program of Jiangsu Province(No.BE201740)the Innovative Talents Promotion Project of Shaanxi Province(No.2019KJXX-064)。
文摘The rapid in situ inhibition of bacterial contamination and subsequent infection without inducing drug resistance is highly vital for the successful implantation and long-term service of titanium(Ti)-based orthopedic implants.However,the instability and potential cytotoxicity of current coatings have deterred their clinical practice.In this study,anodic oxidized titania nanotubes(TNT)were modified with antibacterial polyhexamethylene guanidine(PG)with the assistance of 3,4-dihydroxyphenylacetic acid.Interestingly,the prepared TNT-PG coating exhibited superior in vitro antibacterial activity than flat Ti-PG coating and effectively killed typical pathogens such as Escherichia coli and superbug methicillinresistant Staphylococcus aureus with above 4-log reduction(>99.99%killed)in only 5 min.TNT-PG coating also exerted excellent hemocompatibility with red blood cells and nontoxicity toward mouse pre-osteoblasts(MC3 T3-E1)in 1 week of coculture.In addition,the efficient in vivo anti-infective property of this coating was observed in a rat subcutaneous infection model.More importantly,TNT-PG coating improved the expression of alkaline phosphatase and enhanced the extracellular matrix mineralization of pre-osteoblasts,denoting its osteoinductive capacity.This versatile TNT-PG coating with excellent antibacterial activity and biocompatibility could be a promising candidate for advanced orthopedic implant applications.
基金supported by the National Key Research and Development Program of China(No.2022YFC2304500,No.2021YFC2301800)the National Natural Science Foundation of China(No.81870425)+1 种基金the Fundamental Research Funds for the Central Universities(2023QZJH50)the Medical and Health Research Project of Zhejiang Province(2022RC141).
文摘Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.Methods:We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024.Data on demographics,clinical features,microbiology,treatment,and outcomes were collected.Results:A total of 1,783 infection episodes were recorded,including 1,668 first infections and 115 second infections.Most infections were community-acquired(86.6%).Pneumonia was the most common infection type(26.7%),followed by spontaneous bacterial peritonitis(19.5%)and spontaneous bacteremia(14.1%).Among 754 pathogens isolated from 620 patients,Klebsiella pneumoniae(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of all isolates,with extended-spectrum p-lactamase-producing Escherichia coli being the most prevalent MDR strain(8.9%of patients).Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study(21.5%vs.61.2%,P<0.001),accompanied by a lower clinical resolution rate(63.5%vs.79.8%,P<0.001).Conclusions:The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions.These findings highlight the need for region-specific management and prevention strategies,particularly in light of the changing microbiological landscape,high MDR prevalence,and suboptimal antibiotic practices.
基金supported by the National Natural Science Foundation of China(52003222 and 21875189)Ningbo Natural Science Foundation(202003N4064)+2 种基金the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0752)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(2020GXLH-Z-013)the Fundamental Research Funds for the Central Universities.
文摘Bacterial infections are grave threats to human health,particularly those caused by the most common Grampositive bacteria.The massive administration of broad-spectrum antibiotics to treat various bacterial infections has led to the evolution and spread of drug resistance.As a universal antimicrobial technique unapt to induce drug resistance,photothermal therapy(PTT)is attracting extensive attention in recent years.However,its unspecific killing capability and side effects towards adjacent mammalian cells severely impede the practical applications.Herein,we proposed a metabolic engineering strategy to selectively inactivate Gram-positive bacteria by PTT.A bioorthogonal photothermal agent was prepared by the conjugation of IR-780 iodide and dibenzocyclooctyne(IR780-DBCO).Upon pre-metabolizing with 3-azido-D-alanine,Gram-positive bacteria rather than Gramnegative ones,such as Staphylococcus aureus and vancomycinresistant Enterococcus faecalis(VRE),could be specifically tied up by the explosive IR780-DBCO via copper-free click chemistry.Thereafter,they spontaneously detonated under 15 min near-infrared light irradiation and inactivated nearly 100% Gram-positive bacteria in vitro.Moreover,superbug VRE-induced infection was significantly inhibited by this approach in a mouse skin wound model.This metabolic labelling-based photothermal ablation strategy specific to Gram-positive microbes would stimulate the development of precise antibacterial candidates for preclinical applications.
