Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to stu...Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.展开更多
Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disinteg...Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.展开更多
Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence fact...Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.展开更多
Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-ass...Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-associated pneumonia (HCAP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Retrospective analysis data. Data were collected for adult patients admitted to King Faisal Specialist Hospital and Research Centre-Jeddah (KFSH & RC-J) from January 2010 to May 2015. Method: A total of 88 patients with HAP, VAP and HCAP caused by MRSA treated with vancomycin (IV) or linezolid (IV or PO) either as empirically or directed therapy ≥ 7 days. They are retrospectively evaluated and analyzed. The primary end points are morbidity and mortality rate as well as clinical cure rate. The secondary end point is the cost analysis for each medication. Results: A total of 40 patients (ICU, n = 13 (32.5% and non ICU, n = 27 (67.5%)) were included in the study. Among vancomycin, n = 21 (52.5%);age (54.95 ± 18.255) and linezolid, n = 19 (74.5%);age (48.684 ± 25.593), there was no statistical differences in mortality and morbidity rate (P = 0.375). Clinical cure rate (fever improvement, 12 (57.1%) vs 12 (63.2%);P = 0.698, leukocytosis improvement, 15 (71.4%) vs 14 (73.7%);P = 0.873, purulent sputum improvement, 6 (28.6%) vs 4 (21.1%);P = 0.429, dyspnea improvement, 8 (38.1%) vs 3 (15.8%);P = 0.115,cough improvement 4 (19.0%) vs 4 (21.1%);P = 0.592, microbiological eradication of MRSA from sputum culture, 2 (9.5%) vs 6 (31.6%);P = 0.089 and improvement of radiographic finding (pulmonary infiltration), 17 (81.0%) vs 16 (84.2%);P = 0.559) of vancomycin vs linezolid, respectively. The cost analysis in the treatment of MRSA pneumonia with linezolid is statistical significantly higher than vancomycin. The mean cost of vancomycin = 185.9143 SR and of linezolid = 4547.3684 SR (P Conclusion: There are no statistical differences in mortality and morbidity rate and clinical cure rate between linezolid and vancomycin in the treatment of MRSA in HAP, VAP, and HCAP. However, the cost of linezlid is significantly higher than vancomycin during the treatment period of one patient.展开更多
Resistance against commonly used antibiotics is a serious clinical problem in recent medical practice. There exist several bacterial strains in which the possibilities of their inhibition are very limited due to multi...Resistance against commonly used antibiotics is a serious clinical problem in recent medical practice. There exist several bacterial strains in which the possibilities of their inhibition are very limited due to multidrug resistance. Antimicrobial photodynamic therapy (aPDT) represents an option how to effectively suppress the growth of resistant pathogens. In this work we have studied interactions of potent photosensitizer hypericin (Hyp) with hospital-related gram positive (Gram+) and gram negative (Gram-) bacterial strains and the effects of photodynamic activated Hyp on bacterial susceptibility and/or resistance of these strains to antibiotics. We demonstrated a significant influence of photoactivated Hyp on growth of Staphylococcus aureus and Enterococcus sp. We have also shown that it is extremely important to use the effective concentrations of Hyp for aPDT, which completely inhibit the growth of microorganisms. Otherwise, there appears an increase in resistance, probably due to the activation of efflux mechanisms, which are involved in the efflux of Hyp and antibiotics as well.展开更多
Background The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) maybe changed by strict infection control measures,and the impact of empirical antibiotic therapy on the outcomes of MRSA infection w...Background The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) maybe changed by strict infection control measures,and the impact of empirical antibiotic therapy on the outcomes of MRSA infection was not clear.We aimed to investigate the present epidemiological status of MRSA infection and empirical antibiotic therapy for MRSA infection in university teaching hospitals in China's Mainland.Methods The present study was a multicenter prospective observational study conducted in five university teaching hospitals.Patients who were consecutively admitted to the intensive care unit and signed a consent form from March 3,2011 to May 31,2011 were included.Patients with age 〈18 years or with a length of hospital stay 〈48 hours were excluded from this study.The following variables were collected or recorded:demographic data,general status,APACHE Ⅱ score of the patient at the time of admission,infections,and the use of antibiotics during a stay.Primary outcomes and prognostic indicators included length of hospital stay and 28-day and 90-day mortality.The differences between the patients with appropriate empirical therapy and patients with inappropriate therapy were analyzed to detect the influences of antibiotic therapy on the prognosis of MRSA infection.Results A total of 682 cases were enrolled.Thirty (66.2%) of 88 MRSA cases were treated with effective antibiotics for MRSA infection; only 20% received appropriate empirical antibiotic treatment.The empirical therapy group compared with the target therapy group had a shorter length of stay,but there were no significant differences in mortality rates.There were no significant differences in the length of hospital stay,length of stay,and 28-day and 90-day mortality between MRSA-infected patients who received or not received effective antibiotics.Two hundred and eighteen cases received sensitive antibiotics for MRSA.Conclusions The MRSA infection rates are at relatively low levels in university teaching hospitals in China.The empirical use of sensitive antibiotics for MRSA infection was at relatively high rate,and there is a tendency of overusing in patients without MRSA infection.On the other hand,the rate of appropriate empirical antibiotic therapy for patients with MRSA infection is relatively low.展开更多
Background The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of...Background The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of hVISA is rare in China. This study summarizes the prevalence and clinical features associated with hVISA infections at our institution and the local impact they have on clinical outcome. Methods A total of 122 methicillin-resistant Staphylococcus aureus (MRSA) isolates which were of the causative pathogens were collected. One hundred and two patients for whom we had full information of MRSA pneumonia were included. Isolates of MRSA were collected using PCR to detect the mecA gene. Both Etest and macro Etest were performed to screen for hVISA. The Staphylococcal chromosome cassette mec (SCCmec) types were determined by multiplex PCR strategy. Logistic regression analysis was used to determine the risk factors. Results Among the 122 MRSA isolates collected, 25 (20.5%) strains were identified as hVISA. There were 119 (97.5%) SCCmec III isolates, two (1.6%) SCCmec II isolates, and one (0.8%) SCCmec V isolate. The 30-day mortality of MRSA-hospital acquired pneumonia (HAP) was 37.3%, and 62.5% for hVISA-HAP. Vancomycin treatment was the independent risk factor of hVISA. Factors independently associated with 30-day mortality in all patients were acute physiology and Chronic Health Evaluation (APACHE) II score 〉20, multiple lobe lesions, and creatinine clearance rate (CCR) 〈15 ml/min. Conclusions The prevalence of hVISA is 20.5% at our institution, hVISA-HAP patients had a poor clinical outcome. Vancomycin treatment was the independent predictors for hVISA infection. Factors independently associated with 30-day mortality in all patients were APACHE II score 〉20, multiple lobe lesions and CCR 〈15 ml/min.展开更多
A 50-year old woman, without any underlying disease, presented with pneumonia after experiencing flu-like symptoms. Streptococcus pneumoniae was identified on admission through blood culture and urine antigen tests. S...A 50-year old woman, without any underlying disease, presented with pneumonia after experiencing flu-like symptoms. Streptococcus pneumoniae was identified on admission through blood culture and urine antigen tests. Staphylococcus aureus and Streptococcus pneumoniae were present in the sputum culture. Computed tomography showed cavity development in the consolidation areas, typical of staphylococcal pneumonia. The patient was intubated and received mechanical ventilation as respiratory failure progressed. She exhibited improvement following antibiotic therapy. The change in type B influenza virus serum titer confirmed that this was a unique case of severe pneumonia caused by multiple bacterial organisms following type B influenza virus infection.展开更多
Antibiotic resistance has been compromised hospitalized patients with serious infections. The main cases of bacteremia can be caused by antibiotic resistant pathogens. Photodynamic therapy (PDT) has been shown as an...Antibiotic resistance has been compromised hospitalized patients with serious infections. The main cases of bacteremia can be caused by antibiotic resistant pathogens. Photodynamic therapy (PDT) has been shown as an alternative for inactivation of microorganisms in blood. In this therapy photochemical mechanisms occur that may prevent the development of bacteria. This study aims optimization of PDT parameters for blood decontamination. Concentration ofphotosensitizer (PS), light dose (LD) and incubation time (IT) were studied for hemolysis and cell toxic effects. It was observed that PDT can be used for microbial inactivation in total blood reducing 0.85 log10 CFU/mL ofS. aureus at 15 J/cm^2 and 50μg/mL of Photogem .展开更多
基金National Science and Technology Major Project,Grant/Award Number:2016YFD0500208,2017ZX10304402-001-012 and 2017ZX10304402-001-006Shanghai Science and Technology Commission“R&D public service platform and institutional capacity improvement project”,Grant/Award Number:21DZ2291300Shanghai Public Health Clinical Center projects,Grant/Award Number:KY-GW-2021-39,KY-GW-2019-19 and KY-GW-2019-11。
文摘Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.
基金supported by the National Natural Science Foundation of China(U22A20523,32172912,and 32102722)the Interdisciplinary Integration and Innovation Project of Jilin University(JLUXKJC2021QZ04)。
文摘Host-directed therapy(HDT)is an emerging novel approach for treating multidrug-resistant Staphylococcus aureus(S.aureus)infection.Functioning as the indispensable specific cellular receptor for a-toxin(Hla),a-disintegrin and metalloproteinase 10(ADAM10)is exploited to accelerate S.aureus infection through diverse mechanisms.The extraordinary contribution of ADAM10 to S.aureus pathogenesis renders it an attractive HDT target for combating S.aureus infection.Our study is the first to demonstrate the indispensable role of ADAM10 in S.aureus-induced necroptosis,and it enhances our knowledge of the role of ADAM10 in S.aureus infection.Using a fluorogenic substrate assay,we further identified kaempferol as a potent ADAM10 inhibitor that effectively protected mice from S.aureus infection by suppressing Hla-mediated barrier disruption and necroptosis.Collectively,our work presents a novel hostdirected therapeutic strategy for using the promising candidate kaempferol to treat S.aureus infection and other diseases relevant to the disordered upregulation of ADAM10.
文摘Staphylococcus aureus is a dangerous gram positive bacterial pathogen which, not only evades the host’s immune system but also can destroy the leucocytes especially neutrophils. It has an embodiment of virulence factors most of which are secreted. Staphylococcus aureus secretes a number of toxins which cause tissue damage and facilitate spreading and nutrients uptake. Among the toxins, hemolysins α, β, γ, δ and Panton Valentine Leukocidin (PVL) are unique that they drill pores in the membrane, leading to the efflux of vital molecules and metabolites. Hemolysins also help in the scavenging of iron, although many of them also have leucolytic properties. α-hemolysin, also known as α-toxin, is the most prominent cytotoxin which damages a wide range of host cells including epithelial cells, endothelial cells, erythrocytes, monocytes, keratinocytes and it damages cell membrane and induces apoptosis. β-Hemolysin significantly affects human immune cell function. It has Mg2+ dependent sphingomyelinase activity and degrades sphingomyelin of plasma membrane into phosphorylcholine and ceramides. The bi-component leukocidins, which include γ-hemolysin and PVL, attack human phagocytic cells and greatly contribute to immune evasion. Delta toxin is a low molecular weight exotoxin with a broad cytolytic activity. Virulence determinants, quorum sensing and biofilm synthesis provide some attractive targets for design and development of a new group of antimicrobial compounds. This review provides an update on the structure, biological functions of hemolysins and their role in quorum sensing/biofilm synthesis (if any) and as effective therapeutic targets for anti-virulence drug development. We have tried to bring together information available on various aspects of hemolysins and highlighted their distribution among all species of Staphylococcus and other bacteria. We have updated the status of development of candidate drugs targeting the hemolysins for anti-virulence therapy as it offers an additional strategy to reduce the severity of infection and which would, through quorum quenching, delay the development biofilms leading to drug resistance.
文摘Aim: To evaluate morbidity and mortality rate, clinical cure rate and cost of linezolid versus vancomycin in patients who have hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP) or Healthcare-associated pneumonia (HCAP) caused by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Retrospective analysis data. Data were collected for adult patients admitted to King Faisal Specialist Hospital and Research Centre-Jeddah (KFSH & RC-J) from January 2010 to May 2015. Method: A total of 88 patients with HAP, VAP and HCAP caused by MRSA treated with vancomycin (IV) or linezolid (IV or PO) either as empirically or directed therapy ≥ 7 days. They are retrospectively evaluated and analyzed. The primary end points are morbidity and mortality rate as well as clinical cure rate. The secondary end point is the cost analysis for each medication. Results: A total of 40 patients (ICU, n = 13 (32.5% and non ICU, n = 27 (67.5%)) were included in the study. Among vancomycin, n = 21 (52.5%);age (54.95 ± 18.255) and linezolid, n = 19 (74.5%);age (48.684 ± 25.593), there was no statistical differences in mortality and morbidity rate (P = 0.375). Clinical cure rate (fever improvement, 12 (57.1%) vs 12 (63.2%);P = 0.698, leukocytosis improvement, 15 (71.4%) vs 14 (73.7%);P = 0.873, purulent sputum improvement, 6 (28.6%) vs 4 (21.1%);P = 0.429, dyspnea improvement, 8 (38.1%) vs 3 (15.8%);P = 0.115,cough improvement 4 (19.0%) vs 4 (21.1%);P = 0.592, microbiological eradication of MRSA from sputum culture, 2 (9.5%) vs 6 (31.6%);P = 0.089 and improvement of radiographic finding (pulmonary infiltration), 17 (81.0%) vs 16 (84.2%);P = 0.559) of vancomycin vs linezolid, respectively. The cost analysis in the treatment of MRSA pneumonia with linezolid is statistical significantly higher than vancomycin. The mean cost of vancomycin = 185.9143 SR and of linezolid = 4547.3684 SR (P Conclusion: There are no statistical differences in mortality and morbidity rate and clinical cure rate between linezolid and vancomycin in the treatment of MRSA in HAP, VAP, and HCAP. However, the cost of linezlid is significantly higher than vancomycin during the treatment period of one patient.
文摘Resistance against commonly used antibiotics is a serious clinical problem in recent medical practice. There exist several bacterial strains in which the possibilities of their inhibition are very limited due to multidrug resistance. Antimicrobial photodynamic therapy (aPDT) represents an option how to effectively suppress the growth of resistant pathogens. In this work we have studied interactions of potent photosensitizer hypericin (Hyp) with hospital-related gram positive (Gram+) and gram negative (Gram-) bacterial strains and the effects of photodynamic activated Hyp on bacterial susceptibility and/or resistance of these strains to antibiotics. We demonstrated a significant influence of photoactivated Hyp on growth of Staphylococcus aureus and Enterococcus sp. We have also shown that it is extremely important to use the effective concentrations of Hyp for aPDT, which completely inhibit the growth of microorganisms. Otherwise, there appears an increase in resistance, probably due to the activation of efflux mechanisms, which are involved in the efflux of Hyp and antibiotics as well.
文摘Background The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) maybe changed by strict infection control measures,and the impact of empirical antibiotic therapy on the outcomes of MRSA infection was not clear.We aimed to investigate the present epidemiological status of MRSA infection and empirical antibiotic therapy for MRSA infection in university teaching hospitals in China's Mainland.Methods The present study was a multicenter prospective observational study conducted in five university teaching hospitals.Patients who were consecutively admitted to the intensive care unit and signed a consent form from March 3,2011 to May 31,2011 were included.Patients with age 〈18 years or with a length of hospital stay 〈48 hours were excluded from this study.The following variables were collected or recorded:demographic data,general status,APACHE Ⅱ score of the patient at the time of admission,infections,and the use of antibiotics during a stay.Primary outcomes and prognostic indicators included length of hospital stay and 28-day and 90-day mortality.The differences between the patients with appropriate empirical therapy and patients with inappropriate therapy were analyzed to detect the influences of antibiotic therapy on the prognosis of MRSA infection.Results A total of 682 cases were enrolled.Thirty (66.2%) of 88 MRSA cases were treated with effective antibiotics for MRSA infection; only 20% received appropriate empirical antibiotic treatment.The empirical therapy group compared with the target therapy group had a shorter length of stay,but there were no significant differences in mortality rates.There were no significant differences in the length of hospital stay,length of stay,and 28-day and 90-day mortality between MRSA-infected patients who received or not received effective antibiotics.Two hundred and eighteen cases received sensitive antibiotics for MRSA.Conclusions The MRSA infection rates are at relatively low levels in university teaching hospitals in China.The empirical use of sensitive antibiotics for MRSA infection was at relatively high rate,and there is a tendency of overusing in patients without MRSA infection.On the other hand,the rate of appropriate empirical antibiotic therapy for patients with MRSA infection is relatively low.
基金This research was supported by a grant from the National Natural Science Foundation of China
文摘Background The emergence of heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) is increasingly challenging the methods for detection in diagnostic microbiology laboratories. However, the report of hVISA is rare in China. This study summarizes the prevalence and clinical features associated with hVISA infections at our institution and the local impact they have on clinical outcome. Methods A total of 122 methicillin-resistant Staphylococcus aureus (MRSA) isolates which were of the causative pathogens were collected. One hundred and two patients for whom we had full information of MRSA pneumonia were included. Isolates of MRSA were collected using PCR to detect the mecA gene. Both Etest and macro Etest were performed to screen for hVISA. The Staphylococcal chromosome cassette mec (SCCmec) types were determined by multiplex PCR strategy. Logistic regression analysis was used to determine the risk factors. Results Among the 122 MRSA isolates collected, 25 (20.5%) strains were identified as hVISA. There were 119 (97.5%) SCCmec III isolates, two (1.6%) SCCmec II isolates, and one (0.8%) SCCmec V isolate. The 30-day mortality of MRSA-hospital acquired pneumonia (HAP) was 37.3%, and 62.5% for hVISA-HAP. Vancomycin treatment was the independent risk factor of hVISA. Factors independently associated with 30-day mortality in all patients were acute physiology and Chronic Health Evaluation (APACHE) II score 〉20, multiple lobe lesions, and creatinine clearance rate (CCR) 〈15 ml/min. Conclusions The prevalence of hVISA is 20.5% at our institution, hVISA-HAP patients had a poor clinical outcome. Vancomycin treatment was the independent predictors for hVISA infection. Factors independently associated with 30-day mortality in all patients were APACHE II score 〉20, multiple lobe lesions and CCR 〈15 ml/min.
文摘A 50-year old woman, without any underlying disease, presented with pneumonia after experiencing flu-like symptoms. Streptococcus pneumoniae was identified on admission through blood culture and urine antigen tests. Staphylococcus aureus and Streptococcus pneumoniae were present in the sputum culture. Computed tomography showed cavity development in the consolidation areas, typical of staphylococcal pneumonia. The patient was intubated and received mechanical ventilation as respiratory failure progressed. She exhibited improvement following antibiotic therapy. The change in type B influenza virus serum titer confirmed that this was a unique case of severe pneumonia caused by multiple bacterial organisms following type B influenza virus infection.
文摘Antibiotic resistance has been compromised hospitalized patients with serious infections. The main cases of bacteremia can be caused by antibiotic resistant pathogens. Photodynamic therapy (PDT) has been shown as an alternative for inactivation of microorganisms in blood. In this therapy photochemical mechanisms occur that may prevent the development of bacteria. This study aims optimization of PDT parameters for blood decontamination. Concentration ofphotosensitizer (PS), light dose (LD) and incubation time (IT) were studied for hemolysis and cell toxic effects. It was observed that PDT can be used for microbial inactivation in total blood reducing 0.85 log10 CFU/mL ofS. aureus at 15 J/cm^2 and 50μg/mL of Photogem .