BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae inf...BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.展开更多
目的分析多重用药的老年细菌性肺炎住院患者药品不良反应(Adverse Drug Reaction,ADR)特点及相关影响因素。方法回顾性分析2018年1月1日至2022年11月30日于首都医科大学宣武医院住院的老年细菌性肺炎患者情况,采用Naranjo评定法评价药物...目的分析多重用药的老年细菌性肺炎住院患者药品不良反应(Adverse Drug Reaction,ADR)特点及相关影响因素。方法回顾性分析2018年1月1日至2022年11月30日于首都医科大学宣武医院住院的老年细菌性肺炎患者情况,采用Naranjo评定法评价药物与ADR之间的关联性,采用《不良事件通用术语评价标准》(5.0版)对ADR的严重程度进行分级;运用向后选择法建立Logistic回归方程对危险因素进行分析。结果4967例老年细菌性肺炎住院患者中有385名患者发生464例次ADR,发生率为7.75%。ADR类型主要分布在胃肠系统(40.52%)、循环系统(14.44%)及肝功能损伤(12.28%)等。ADR共涉及相关药物671例次,主要为抗感染药物(63.79%)、抗凝药(6.56%)和抗血小板药物(6.41%)。ADR严重程度主要为1级(30.17%)和2级(59.91%)。多因素Logistic回归结果显示,住院天数、用药种数、药物过敏史、女性患者、脑血管疾病和结缔组织病会增加患者发生ADR的风险。结论通过分析老年细菌性肺炎患者发生ADR的危险因素,提示临床应加强对高风险患者ADR的监护与管理,为未来进一步开发老年细菌性肺炎住院患者ADR风险预测模型提供参考。展开更多
基金supported by the National Natural Science Foundation of China(82072148)Zhejiang Provincial Basic Public Welfare Research Program of Zhejiang Province(LGF21H150002)+1 种基金Zhejiang Medicine and Health Science and Technology Project(2022RC245&2023KY255)Ningbo Municipal Natural Science Foundation(2023J134).
文摘BACKGROUND:Streptococcus pneumoniae(S.pneumoniae)is a common pathogen that causes bacterial pneumonia.However,with increasing bacterial resistance,there is an urgent need to develop new drugs to treat S.pneumoniae infections.Nanodefensin with a 14-carbon saturated fatty acid(ND-C14)is a novel nanoantimicrobial peptide designed by modifying myristic acid at the C-terminus of humanα-defensin 5(HD5)via an amide bond.However,it is unclear whether ND-C14 is effective against lung infections caused by S.pneumoniae.METHODS:In vitro,three groups were established,including the control group,and the HD5 and ND-C14 treatment groups.A virtual colony-count assay was used to evaluate the antibacterial activity of HD5 and ND-C14 against S.pneumoniae.The morphological changes of S.pneumoniae treated with HD5 or ND-C14 were observed by scanning electron microscopy.In vivo,mice were divided into sham,vehicle,and ND-C14 treatment groups.Mice in the sham group were treated with 25μL of phosphate-buffered saline(PBS).Mice in the vehicle and ND-C14 treatment groups were treated with intratracheal instillation of 25μL of bacterial suspension with 2×108 CFU/mL(total bacterial count:5×10^(6) CFU),and then the mice were given 25μL PBS or intratracheally injected with 25μL of ND-C14(including 20μg or 50μg),respectively.Survival rates were evaluated in the vehicle and ND-C14 treatment groups.Bacterial burden in the blood and bronchoalveolar lavage fluid were counted.The lung histology of the mice was assessed.A propidium iodide uptake assay was used to clarify the destructive eff ect of ND-C14 against S.pneumoniae.RESULTS:Compared with HD5,ND-C14 had a better bactericidal eff ect against S.pneumoniae because of its stronger ability to destroy the membrane structure of S.pneumoniae in vitro.In vivo,ND-C14 significantly delayed the death time and improved the survival rate of mice infected with S.pneumoniae.ND-C14 reduced bacterial burden and lung tissue injury.Moreover,ND-C14 had a membrane permeation eff ect on S.pneumoniae,and its destructive ability increased with increasing ND-C14 concentration.CONCLUSION:The ND-C14 may improve bactericidal eff ects on S.pneumoniae both in vitro and in vivo.
文摘目的分析多重用药的老年细菌性肺炎住院患者药品不良反应(Adverse Drug Reaction,ADR)特点及相关影响因素。方法回顾性分析2018年1月1日至2022年11月30日于首都医科大学宣武医院住院的老年细菌性肺炎患者情况,采用Naranjo评定法评价药物与ADR之间的关联性,采用《不良事件通用术语评价标准》(5.0版)对ADR的严重程度进行分级;运用向后选择法建立Logistic回归方程对危险因素进行分析。结果4967例老年细菌性肺炎住院患者中有385名患者发生464例次ADR,发生率为7.75%。ADR类型主要分布在胃肠系统(40.52%)、循环系统(14.44%)及肝功能损伤(12.28%)等。ADR共涉及相关药物671例次,主要为抗感染药物(63.79%)、抗凝药(6.56%)和抗血小板药物(6.41%)。ADR严重程度主要为1级(30.17%)和2级(59.91%)。多因素Logistic回归结果显示,住院天数、用药种数、药物过敏史、女性患者、脑血管疾病和结缔组织病会增加患者发生ADR的风险。结论通过分析老年细菌性肺炎患者发生ADR的危险因素,提示临床应加强对高风险患者ADR的监护与管理,为未来进一步开发老年细菌性肺炎住院患者ADR风险预测模型提供参考。
