Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infect...Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.展开更多
Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression...Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression of MRP in the carcinoma tissues of 52 patients with gastric carcinoma and 20 cases with renal cell carcinoma. Results The positive expression rate of MRP was 38.5% (20/52) in gastric carcinoma tissues, and 60% (12/20) in renal carcinoma tissues. The expression of MRP both on cellular membrane and in cytoplasm was observed, but the expression in cytoplasm (thick granule) was more obvious. The positive expression rates of MRP in advanced gastric and renal carcinoma (Ⅲ orⅣ stage) were 60% (15/25) and 88.90% (8/9) reSPectively, which were higher than those in early lesion (Ⅰ or Ⅱ stage, 18.5% and 36.4% respectively). Furthermore, the patients with positive expression of MRP in gastric carcinoma tissues had shorter mean survival time and lower 5-year survival rate than that with negative eopression of MRP. Conclusion MRP plays an important role in the infiltration and metastasis of gastric and renal carcinoma and might contribute to the intrinsic drug - resistance in both carcinomas.展开更多
目的:分析重症监护病区(Intensive Care Unit,ICU)多重耐药菌医院感染特点,为多重耐药菌医院感染防控提供依据。方法:对ICU多重耐药菌医院感染发生情况进行前瞻性监测,描述性分析2016-2018年ICU多重耐药菌医院感染发生情况、菌株构成以...目的:分析重症监护病区(Intensive Care Unit,ICU)多重耐药菌医院感染特点,为多重耐药菌医院感染防控提供依据。方法:对ICU多重耐药菌医院感染发生情况进行前瞻性监测,描述性分析2016-2018年ICU多重耐药菌医院感染发生情况、菌株构成以及感染部位分布,比较不同多重耐药菌菌株的医院感染部位构成、不同类型I CU分布的区别。结果:2016-2018年I CU共发生多重耐药菌医院感染197例次,医院感染发生率为2.73%、千住院日医院感染率为5.40‰;耐碳青霉烯类鲍曼不动杆菌为外科、呼吸和心外ICU最常见的多重耐药菌医院感染菌株,急诊ICU最常见的多重耐药菌医院感染菌株为耐碳青霉烯类肠杆菌科细菌;ICU多重耐药菌医院感染菌株构成:耐碳青霉烯类鲍曼不动杆菌59.39%,耐碳青霉烯类肠杆菌科细菌20.81%,耐碳青霉烯类铜绿假单胞菌16.75%,耐甲氧西林金黄色葡萄球菌3.05%;多重耐药菌的医院感染部位以呼吸系统、血流感染和切口感染为主,其中耐碳青霉烯类鲍曼不动杆菌、耐碳青霉烯类肠杆菌科细菌和耐碳青霉烯类铜绿假单胞菌的医院感染主要发生于呼吸系统,耐甲氧西林金黄色葡萄球菌医院感染部位以血流感染为主,泌尿道感染的常见多重耐药菌为耐碳青霉烯类肠杆菌科细菌。结论:ICU是多重耐药菌医院感染高发科室,应根据医院感染特点,在诊疗护理中采取针对性防控措施,尤其是对重点菌株及其重点部位医院感染的监测与防控。展开更多
Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery...Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems（sof-DDSs） can adsorb dianionic pemetrexed（PMX）,a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems展开更多
Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia especially with the recent escalating trend in the management of pediatric cancer patients towards intensifi...Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: Monitoring if a change has occurred in pattern of blood stream infections (BSI) in febrile neutropenic (FN) pediatric cancer patients. Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, and prolonged duration of episodes when compared to previous surveillance, with a p value of <0.001, 0.005, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, 6% in 2011 and 10% in 2006. Conclusion: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and prolonged episodes.展开更多
Objective:To assess potential risk factors for diabetic foot ulcers infected with multidrug-resistant-organisms(MDROs)and to investigate antibiotic susceptibility patterns and extended-spectrum-β-lactamase(ESBL)-prod...Objective:To assess potential risk factors for diabetic foot ulcers infected with multidrug-resistant-organisms(MDROs)and to investigate antibiotic susceptibility patterns and extended-spectrum-β-lactamase(ESBL)-production in bacteria isolated from these ulcers.Methods:Seventy-seven diabetic foot ulcer-patients were studied in a consecutive series.Forty-four study factors were recorded for each patient.Specimens were obtained by scraping the ulcer base or the deep portion of the wound edge with a sterile curette.The soft tissue specimens were quickly sent to the laboratory and processed for microbial pathogens.Gram-negative bacterial isolates were tested for ESBL production by double-disc-diffusion method.The association of study variables with MDRO and non-MDRO infection status of ulcers was tested by Student's t test or Fisher's exact test using SPSS(version 11.5,Chicago).Results:An alarming number of patients were MDRO-positive(72.7%).ESBL-positive strains constituted 19.8% of total isolates.Staphylococcal isolates identified as methicillin-resistant Staphylococcus aureus(MRSA)and vancomycin-resistant Staphylococcus aureus(VRSA),were 3.7%(n=8)and 0.5%(n=1)respectively.Twenty-two study factors were found to be significantly associated with MDRO infection status of ulcers in the univariate analysis.Multiple logistic regressions proved that MDRO status was the only significant,independent predictor of glycemic control(Odds ratio = 4.22,P<0.01).Conclusion:It is concluded that MDRO infected patients have poor glycemic control.Imipenem and linezolid can be suggested as the drugs of choice in the described setting.展开更多
BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane tr...BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane transport effects.AIM To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance.METHODS Twelve adult rats were included in this study;baseline hepatic and renal laboratory values and digoxin pharmacokinetic(PK)studies were established before evenly dividing them into two groups to undergo bile duct ligation(BDL)or a sham procedure.After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction.Data were analyzed using SigmaStat 3.5.Means between pre-surgery and post-surgery in the same experimental group were compared by paired t-test,while independent t-test was employed to compare the means between sham and BDL groups.RESULTS Digoxin clearance was decreased and liver function,but not renal function,was impaired in BDL rats.BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine.Organic anion transporting polypeptides(OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL.OATP4C1 expression was markedly increased in the kidney following BDL.CONCLUSION The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis.These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.展开更多
文摘Bacterial infections are a leading cause of morbidity and mortality among solid organ transplant recipients.Over the last two decades,various multidrug-resistant(MDR)pathogens have emerged as relevant causes of infection in this population.Although this fact reflects the spread of MDR pathogens in health care facilities worldwide,several factors relating to the care of transplant donor candidates and recipients render these patients particularly prone to the acquisition of MDR bacteria and increase the likelihood of MDR infectious outbreaks in transplant units.The awareness of this high vulnerability of transplant recipients to infection leads to the more frequent use of broad-spectrum empiric antibiotic therapy,which further contributes to the selection of drug resistance.This vicious cycle is difficult to avoid and leads to a scenario of increased complexity and narrowed therapeutic options.Infection by MDR pathogens is more frequently associated with a failure to start appropriate empiric antimicrobial ther-apy.The lack of appropriate treatment may contribute to the high mortality occurring in transplant recipients with MDR infections.Furthermore,high therapeutic failure rates have been observed in patients infected with extensively-resistant pathogens,such as carbapenemresistant Enterobacteriaceae,for which optimal treatment remains undefined.In such a context,the careful implementation of preventive strategies is of utmost importance to minimize the negative impact that MDR infections may have on the outcome of liver transplant recipients.This article reviews the current literature regarding the incidence and outcome of MDR infections in liver transplant recipients,and summarizes current preventive and therapeutic recommendations.
文摘Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression of MRP in the carcinoma tissues of 52 patients with gastric carcinoma and 20 cases with renal cell carcinoma. Results The positive expression rate of MRP was 38.5% (20/52) in gastric carcinoma tissues, and 60% (12/20) in renal carcinoma tissues. The expression of MRP both on cellular membrane and in cytoplasm was observed, but the expression in cytoplasm (thick granule) was more obvious. The positive expression rates of MRP in advanced gastric and renal carcinoma (Ⅲ orⅣ stage) were 60% (15/25) and 88.90% (8/9) reSPectively, which were higher than those in early lesion (Ⅰ or Ⅱ stage, 18.5% and 36.4% respectively). Furthermore, the patients with positive expression of MRP in gastric carcinoma tissues had shorter mean survival time and lower 5-year survival rate than that with negative eopression of MRP. Conclusion MRP plays an important role in the infiltration and metastasis of gastric and renal carcinoma and might contribute to the intrinsic drug - resistance in both carcinomas.
文摘目的:分析重症监护病区(Intensive Care Unit,ICU)多重耐药菌医院感染特点,为多重耐药菌医院感染防控提供依据。方法:对ICU多重耐药菌医院感染发生情况进行前瞻性监测,描述性分析2016-2018年ICU多重耐药菌医院感染发生情况、菌株构成以及感染部位分布,比较不同多重耐药菌菌株的医院感染部位构成、不同类型I CU分布的区别。结果:2016-2018年I CU共发生多重耐药菌医院感染197例次,医院感染发生率为2.73%、千住院日医院感染率为5.40‰;耐碳青霉烯类鲍曼不动杆菌为外科、呼吸和心外ICU最常见的多重耐药菌医院感染菌株,急诊ICU最常见的多重耐药菌医院感染菌株为耐碳青霉烯类肠杆菌科细菌;ICU多重耐药菌医院感染菌株构成:耐碳青霉烯类鲍曼不动杆菌59.39%,耐碳青霉烯类肠杆菌科细菌20.81%,耐碳青霉烯类铜绿假单胞菌16.75%,耐甲氧西林金黄色葡萄球菌3.05%;多重耐药菌的医院感染部位以呼吸系统、血流感染和切口感染为主,其中耐碳青霉烯类鲍曼不动杆菌、耐碳青霉烯类肠杆菌科细菌和耐碳青霉烯类铜绿假单胞菌的医院感染主要发生于呼吸系统,耐甲氧西林金黄色葡萄球菌医院感染部位以血流感染为主,泌尿道感染的常见多重耐药菌为耐碳青霉烯类肠杆菌科细菌。结论:ICU是多重耐药菌医院感染高发科室,应根据医院感染特点,在诊疗护理中采取针对性防控措施,尤其是对重点菌株及其重点部位医院感染的监测与防控。
基金the National Natural Science Foundation of China(Nos.21432004,21529201,and 91527301)the Ministry of Science and Technology of China(No.2013CB834501)+1 种基金the Ministry of Education of China Research Fund for the Doctoral Program and of China for financial supportsupport from the Molecular Foundry,Lawrence Berkeley National Laboratory,supported by the Office of Science,Office of Basic Energy Sciences,Scientific User Facilities Division,of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231
文摘Water-soluble three-dimensional porous supramolecular organic frameworks（SOFs） have been demonstrated as a new generation of homogeneous polycationic platforms for anti-cancer drug delivery.The new SOF drug delivery systems（sof-DDSs） can adsorb dianionic pemetrexed（PMX）,a clinically used chemotherapeutic agent instantaneously upon dissolving in water,which is driven by both electrostatic attraction and hydrophobicity.The in situ-prepared PMX@SOFs are highly stable and can avoid important release of the drug during plasm circulation and overcome the multidrug resistance of human breast MCF-7/Adr cancer cells to enter the cancer cells.Acidic microenvironment of cancer cells promotes the release of the drug in cancer cells.Both in vitro and in vivo studies have revealed that sofDDSs considerably improve the treatment efficacy of PMX,leading to 6-12-fold reduction of the IC50 values,as compared with that of PMX alone.The new drug delivery strategy omits the loading process required by most of reported nanoparticle-based delivery systems and thus holds promise for future development of low-cost drug delivery systems
文摘Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: Monitoring if a change has occurred in pattern of blood stream infections (BSI) in febrile neutropenic (FN) pediatric cancer patients. Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, and prolonged duration of episodes when compared to previous surveillance, with a p value of <0.001, 0.005, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, 6% in 2011 and 10% in 2006. Conclusion: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and prolonged episodes.
基金supported by the central facilities and internal funds of Interdisciplinary Biotechnology Unit,AMU,India which are highly acknowledged
文摘Objective:To assess potential risk factors for diabetic foot ulcers infected with multidrug-resistant-organisms(MDROs)and to investigate antibiotic susceptibility patterns and extended-spectrum-β-lactamase(ESBL)-production in bacteria isolated from these ulcers.Methods:Seventy-seven diabetic foot ulcer-patients were studied in a consecutive series.Forty-four study factors were recorded for each patient.Specimens were obtained by scraping the ulcer base or the deep portion of the wound edge with a sterile curette.The soft tissue specimens were quickly sent to the laboratory and processed for microbial pathogens.Gram-negative bacterial isolates were tested for ESBL production by double-disc-diffusion method.The association of study variables with MDRO and non-MDRO infection status of ulcers was tested by Student's t test or Fisher's exact test using SPSS(version 11.5,Chicago).Results:An alarming number of patients were MDRO-positive(72.7%).ESBL-positive strains constituted 19.8% of total isolates.Staphylococcal isolates identified as methicillin-resistant Staphylococcus aureus(MRSA)and vancomycin-resistant Staphylococcus aureus(VRSA),were 3.7%(n=8)and 0.5%(n=1)respectively.Twenty-two study factors were found to be significantly associated with MDRO infection status of ulcers in the univariate analysis.Multiple logistic regressions proved that MDRO status was the only significant,independent predictor of glycemic control(Odds ratio = 4.22,P<0.01).Conclusion:It is concluded that MDRO infected patients have poor glycemic control.Imipenem and linezolid can be suggested as the drugs of choice in the described setting.
文摘BACKGROUND Cardiac and hepatic functionality are intertwined in a multifaceted relationship.Pathologic processes involving one may affect the other through a variety of mechanisms,including hemodynamic and membrane transport effects.AIM To better understand the effect of extrahepatic cholestasis on regulations of membrane transporters involving digoxin and its implication for digoxin clearance.METHODS Twelve adult rats were included in this study;baseline hepatic and renal laboratory values and digoxin pharmacokinetic(PK)studies were established before evenly dividing them into two groups to undergo bile duct ligation(BDL)or a sham procedure.After 7 d repeat digoxin PK studies were completed and tissue samples were taken to determine the expressions of cell membrane transport proteins by quantitative western blot and real-time polymerase chain reaction.Data were analyzed using SigmaStat 3.5.Means between pre-surgery and post-surgery in the same experimental group were compared by paired t-test,while independent t-test was employed to compare the means between sham and BDL groups.RESULTS Digoxin clearance was decreased and liver function,but not renal function,was impaired in BDL rats.BDL resulted in significant up-regulation of multidrug resistance 1 expression in the liver and kidney and its down-regulation in the small intestine.Organic anion transporting polypeptides(OATP)1A4 was up-regulated in the liver but down-regulated in intestine after BDL.OATP4C1 expression was markedly increased in the kidney following BDL.CONCLUSION The results suggest that cell membrane transporters of digoxin are regulated during extrahepatic cholestasis.These regulations are favorable for increasing digoxin excretion in the kidney and decreasing its absorption from the intestine to compensate for reduced digoxin clearance due to cholestasis.
