Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,mon...Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.展开更多
BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneum...BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.展开更多
Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins ...Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.展开更多
Purpose::COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV.However,little is known regarding its characteristics in terms of systemic inflammation and organ injury,especially comp...Purpose::COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV.However,little is known regarding its characteristics in terms of systemic inflammation and organ injury,especially compared with classical bacterial sepsis.This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis.Methods::In this retrospective cohort study,septic patients with COVID-19 in the intensive care unit(ICU)of a government-designed therapy center in Shenzhen,China between January 14,2020 and March 10,2020,and septic patients induced by carbapenem-resistant klebsiella pneumonia(CrKP)admitted to the ICU of the Second People's Hospital of Shenzhen,China between January 1,2014 and October 30,2019 were enrolled.Demographic and clinical parameters including comorbidities,critical illness scores,treatment,and laboratory data,as well as prognosis were compared between the two groups.Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve,respectively.Results::A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled.A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection(indicated by lower PaO 2/FiO 2),but milder systemic inflammatory response,lower sequential organ failure assessment score and better functions of the organs like heart,liver,kidney,coagulation,and circulation.However,the acquired immunosuppression presented in COVID-19 patients was more severe,which presented as lower lymphocyte counts(0.8×109/L vs.0.9×109/L).Moreover,the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients(78.5%vs.38.1%and 6.5%vs.0,respectively)who required less invasive mechanical ventilation(31.6%vs.54.0%).The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis(12.1%vs.39.7%,6.5 days vs.23.0 days and 21.0 days vs.33.0 days,respectively)(all p<0.001).Similar results were obtained after being adjusted by age,gender,comorbidity and PaO2/FiO2.Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death.While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients’hospital stay.Conclusion::Critical COVID-19 shares clinical characteristics with classical bacterial sepsis,but the degree of systemic inflammatory response,secondary organ damage and mortality rate are less severe.However,following 2019-nCoV infection,the level of immunosuppression may be increased and thus induce in more death at the later stage of patients’hospitalstay.展开更多
Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found i...Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.展开更多
Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gramnegative bacteria.Over the last decade,carbapenem-resistant E...Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gramnegative bacteria.Over the last decade,carbapenem-resistant Enterobacteriaceae(CRE)have emerged as organisms causing spontaneous bacterial peritonitis.Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics.Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient,and rapid deescalation of empiric antibiotic treatment is not widely recognized.This review summarizes the molecular characteristics,epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.展开更多
基金supported by grants from Non-Profit Central Research Institute Fund of Chinese Academy of Medical Science(No.2018PT32018)Hubei Science and Technology Plan(No.2017ACA096).
文摘Objective Donor-derived carbapenem-resistant Klebsiella pneumoniae(CRKP)infection has recently emerged as a critical early complication after renal transplantation.Although CRKP is usually sensitive to tigecycline,monotherapy with this drug is often less than effective.We investigated the efficacy of a combined regimen of tigecycline with high-dose,extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.Methods From Jan.2016 to Dec.2017,a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute.Probable or possible donor-derived infection(DDI)was identified in 8 transplant recipients.Clinical data were retrospectively analyzed.Results Klebsiella pneumoniae carbapenemase-2(KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation,leading to surgical site(n=3),urinary tract(n=4),and/or bloodstream(n=2)infections in 8 recipients.The drug susceptibility tests showed that CRKP was sensitive to tigecycline,but resistant to meropenem.In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem,DDIs were successfully cured.The length of hospital stay was 31(18–129)days,and the serum creatinine at discharge was 105.8±16.7µmol/L.The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock.A median follow-up of 43 months(33–55)showed no recurrence of new CRKP infection in the 7 surviving recipients.Conclusion It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.
基金approved by the Ethics Committee of the Third Xiangya Hospital in accordance with the Declaration of Helsinki(No.24029).
文摘BACKGROUND Liver transplantation(LT)is the only curative treatment for end-stage liver disease.However,LT recipients are susceptible to infection,which is the leading cause of early mortality after LT.Klebsiella pneumoniae infections(KPIs)in the bloodstream are common in LT recipients.We hypothesized that KPIs and carbapenemresistant Klebsiella pneumoniae(CRKP)infections may affect the outcomes of LT recipients.AIM To assess KPI incidence,timing,distribution,drug resistance,and risk factors following LT and its association with outcomes.METHODS This retrospective study included 406 patients undergoing LT at The Third Xiangya Hospital of Central South University,a tertiary hospital,from January 2015 to January 2023.We investigated the risk factors for KPIs and assessed the impact of KPIs and CRKP infections on the prognosis of LT recipients using logistic regression analysis.RESULTS KPI incidence was 7.9%(n=32),with lung/thoracic cavity the most frequent site of infection;the median time from LT to KPI onset was 7.5 d.Of 44 Klebsiella pneumoniae isolates,43(97.7%)and 34(77.3%)were susceptible to polymyxin B or ceftazidime/avibactam and tigecycline,respectively;>70%were resistant to piperacillin/tazobactam,ceftazidime,cefepime,aztreonam,meropenem,and levofloxacin.Female sex[odds ratio(OR)=2.827,95%confidence interval(CI):1.256-6.364;P=0.012],pre-LT diabetes(OR=2.794,95%CI:1.070-7.294;P=0.036),day 1 post-LT alanine aminotransferase(ALT)levels≥1500 U/L(OR=3.645,95%CI:1.671-7.950;P=0.001),and post-LT urethral catheter duration over 4 d(OR=2.266,95%CI:1.016-5.054;P=0.046)were risk factors for KPI.CRKP infections,but not KPIs,were risk factors for 6-month all-cause mortality post-LT.CONCLUSION KPIs occur frequently and rapidly after LT.Risk factors include female sex,pre-LT diabetes,increased post-LT ALT levels,and urethral catheter duration.CRKP infections,and not KPIs,affect mortality.
基金supported by the National Natural Science Foundation of China(No.31771189)the Wuhan Health Commission(No.WX18C17 and No.WX19Q31)the Natural Science Foundation of Hubei Province,China(No.2017CFA065 and No.WJ2019H378).
文摘Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.
基金This work was supported by grants from the PLA Logistics Research Project of China[18CXZ030,CWH17L020,17CXZ008]Sanming Project of Medicine in Shenzhen(SZSM20162011)Shenzhen Second People's Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project(Grant No 20173357201815,No 20193357003,No 20203357014).
文摘Purpose::COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV.However,little is known regarding its characteristics in terms of systemic inflammation and organ injury,especially compared with classical bacterial sepsis.This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis.Methods::In this retrospective cohort study,septic patients with COVID-19 in the intensive care unit(ICU)of a government-designed therapy center in Shenzhen,China between January 14,2020 and March 10,2020,and septic patients induced by carbapenem-resistant klebsiella pneumonia(CrKP)admitted to the ICU of the Second People's Hospital of Shenzhen,China between January 1,2014 and October 30,2019 were enrolled.Demographic and clinical parameters including comorbidities,critical illness scores,treatment,and laboratory data,as well as prognosis were compared between the two groups.Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve,respectively.Results::A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled.A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection(indicated by lower PaO 2/FiO 2),but milder systemic inflammatory response,lower sequential organ failure assessment score and better functions of the organs like heart,liver,kidney,coagulation,and circulation.However,the acquired immunosuppression presented in COVID-19 patients was more severe,which presented as lower lymphocyte counts(0.8×109/L vs.0.9×109/L).Moreover,the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients(78.5%vs.38.1%and 6.5%vs.0,respectively)who required less invasive mechanical ventilation(31.6%vs.54.0%).The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis(12.1%vs.39.7%,6.5 days vs.23.0 days and 21.0 days vs.33.0 days,respectively)(all p<0.001).Similar results were obtained after being adjusted by age,gender,comorbidity and PaO2/FiO2.Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death.While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients’hospital stay.Conclusion::Critical COVID-19 shares clinical characteristics with classical bacterial sepsis,but the degree of systemic inflammatory response,secondary organ damage and mortality rate are less severe.However,following 2019-nCoV infection,the level of immunosuppression may be increased and thus induce in more death at the later stage of patients’hospitalstay.
基金the National Natural Science Foundation of China(U1803109)the National Key Research and Development Program of China(2018YFC1602500)+6 种基金the National Natural Science Foundation of China(81572032)Major scientific and technological innovation projects in Shandong Province(2019JZZY010719)National Key Research and Development Program(2019YFA0904003)Six Talent Peaks Project in Jiangsu Province(2016-WSN-112)Key research and development project of Jiangsu provincial science and Technology Department(BE2017654)Gusu key health talent of Suzhou,Jiangsu youth medical talents program(QN-867)the Science and Technology Program of Suzhou(SZS201715)。
文摘Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.
文摘Carbapenem antibiotics were first introduced in the 1980s and have long been considered the most active agents for the treatment of multidrug-resistant gramnegative bacteria.Over the last decade,carbapenem-resistant Enterobacteriaceae(CRE)have emerged as organisms causing spontaneous bacterial peritonitis.Infections caused by CRE have shown a higher mortality rate than those caused by bacteria sensitive to carbapenem antibiotics.Current antibiotic guidelines for the treatment of spontaneous bacterial peritonitis are insufficient,and rapid deescalation of empiric antibiotic treatment is not widely recognized.This review summarizes the molecular characteristics,epidemiology and possible treatment of spontaneous bacterial peritonitis caused by CRE.
基金supported by the National Natural Science Foundation of China(32141001 and 31830001)the National Science Fund for Distinguished Young Scholars(32125003)the National Key R&D Program of China(2022YFC2303900 and 2022YFC3704700)。
