BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles ...BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients.AIM To evaluate the presence,survival and transmission of different multidrug-resistant bacteria(MDRB)from HCP attire onto skin.METHODS Three MDRB[methicillin-resistant Staphylococcus aureus(MRSA);vancomycin-resistant Enterococcus faecium(VRE);carbapenem-resistant Klebsiella pneumoniae,(CRKP)]were inoculated on textiles from scrubs(60%cotton-40%polyester)and white coat(100%cotton)at concentrations of 108 colony-forming units(CFU),105 CFU,and 103 CFU per mL.The inoculation of swatches was divided in time intervals of 1 min,5 min,15 min,30 min,1 h,2 h,3 h,4 h,5 h,and 6 h.At the end of each period,textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media.Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations,for the whole length of the 6-h experiment.RESULTS MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study.VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h,while showing no growth at 103 CFU/mL.CRKP was recovered from 108 CFU/mL for 6 h,up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL.CONCLUSION Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations.The fact that all MDRB can be sustained and transferred to skin even at lower concentrations,supports that textiles are implicated as vectors of bacterial spread.展开更多
AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, labor...AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.展开更多
Objective:To investigate the status of multidrug-resistant bacteria and the prevention and control measures of nosocomial in-fection in our hospital.Methods:The annual monitoring of multidrug-resistant bacteria infect...Objective:To investigate the status of multidrug-resistant bacteria and the prevention and control measures of nosocomial in-fection in our hospital.Methods:The annual monitoring of multidrug-resistant bacteria infection was measured to summarize the bacteria species,statistical distribution and antibiotic resistance.Identification of multidrug-resistant bacteria infection in patients infected or hospital acquired infections was taken to analyze the reasons of multidrug-resistant bacteria strain and put forward the relevant measures.Results:The top five of multidrug-resistant strains infections were:Gram-positive bacteria including methicillin-resistant Staphylococcus aureus,Staphylococcus aureus;Gram-negative bacteria including Escherichia coli,Acinetobacter bauman-nii,Klebsiella pneumoniae.Conclusions:The occurrence of multidrug-resistant hospital infections could be prevented by rational use of antibiotics,hand hygiene and disinfection management,and reinforced monitoring of multidrug-resistant bacteria.展开更多
Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development ...Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host cells.Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications.Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular antibiotics.Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as models.In addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes.Finally,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia.These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.展开更多
Objective: To investigate the antibacterial activities of crude ethanol extracts of 12 Philippine medicinal plants.Methods: Crude ethanol extracts from 12 Philippine medicinal plants were evaluated for their antibacte...Objective: To investigate the antibacterial activities of crude ethanol extracts of 12 Philippine medicinal plants.Methods: Crude ethanol extracts from 12 Philippine medicinal plants were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus, extended spectrum β-lactamase-producing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Results: The leaf extracts of Psidium guajava, Phyllanthus niruri, Ehretia microphylla and Piper betle(P. betle) showed antibacterial activity against the Gram-positive methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus. P. betle showed the highest antibacterial activity for these bacteria in the disk diffusion(16-33 mm inhibition diameter), minimum inhibitory concentration(19-156 μg/m L) and minimum bactericidal concentration(312 μg/m L) assays. P. betle leaf extracts only showed remarkable antibacterial activity for all the Gram-negative multidrug-resistant bacteria(extended spectrum β-lactamaseproducing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing) in the disk diffusion(17-21 mm inhibition diameter), minimum inhibitory concentration(312-625 μg/m L) and minimum bactericidal concentration(312-625 μg/m L) assays. Conclusions: P. betle had the greatest potential value against both Gram-negative and Grampositive multidrug-resistant bacteria. Favorable antagonistic activities were also exhibited by the ethanol extracts of Psidium guajava, Phyllanthus niruri and Ehretia microphylla.展开更多
The study investigated the antibacterial activity of essential oil from the peel of Citrus aurantifolia against eleven multidrug-resistant (MDR) bacterial isolates of clinical origin. The Kirby-Bauer disc diffusion me...The study investigated the antibacterial activity of essential oil from the peel of Citrus aurantifolia against eleven multidrug-resistant (MDR) bacterial isolates of clinical origin. The Kirby-Bauer disc diffusion method was used to determine the antibiotic resistance profile of the isolates. Essential oil (EO) from the peels of lime purchased at a market in Ile-Ife was extracted by the hydro-distillation method, while the sensitivity of the isolates to EO was done via agar well diffusion method. The minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of the EO against the tested isolates were determined following standard methods. All the tested isolates exhibited multidrug resistance (MDR) characteristics. The multiple antibiotics resistant indexes (MARI%) for Gram-positive bacterial isolates ranged between 70% and 100% while that of Gram-negative was 100%. The yield of EO was 1% and the EO demonstrated activities at 25%, 50% and 100% v/v against the MDR bacterial isolates. The activity of EO was mostly not significantly different at the same concentration for all the isolates, and at different concentrations for each of the isolates. The MIC range for Gram-negative and Gram-positive isolates was between 0.195% to 3.125% v/v and 0.39% to 3.125% respectively while the range was between 1.563% to 3.125% and 0.781% to 6.250% v/v for MBC respectively. The study showed that EO from the peel of lime fruits demonstrated excellent in vitro antibacterial activity against MDR bacterial isolates. This potential can be further explored as an alternative for the treatment and management of infections caused by MDR bacterial isolates.展开更多
Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to...Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to May 2020 were selected for the study,of which 73 carried drug-resistant bacteria.Results:The risk factor network of people infected with multidrug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria,and the interaction between risk factors of the former is stronger.Conclusion:Antibiotics must be used appropriately after surgery.When the elderly was abnormal in indicators such as fever and procalcitonin in the ward,they should be considered as high-risk groups of MDRO infection.They need special care and preventive measures.展开更多
Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strat...Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation ofπ-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O_(2)^(·-))and hydroxyl radical(·OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar concentration under a low white light irradiation(30 mW/cm^(2)).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-I photodynamic therapy(PDT)performance for efficient antibacterial treatments,advancing the development of antibacterial agents.展开更多
Sepsis,caused by uncontrollable infection and inflammatory response,leads to more than 30 million infected patients and results in high morbidity worldwide every year.Currently,no efficient approaches have been develo...Sepsis,caused by uncontrollable infection and inflammatory response,leads to more than 30 million infected patients and results in high morbidity worldwide every year.Currently,no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm.Here,we report macrophages loaded with aggregated carbon dots(ACDs)in the lysosome,termed MCDs,to treat sepsis in immunosuppressive mice.The ACDs are constructed by negative CDs and amine-abundant polyethyleneimine(PEI),enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy.The ACDs are specifically located in the macrophage lysosomes,efficiently enhancing the multidrug-resistant bacteria-killing ability of MCDs.More importantly,the MCDs possess superior anti-inflammatory effects such as reducing the number of pro-inflammatory(M1)and stimulating anti-inflammatory(M2)macrophages.These effects upregulate the inflammatory cytokines(TNF-α,IL-1β,IL-4,and IL-10),ultimately resulting in increased sepsis survival.Our work provides an intelligent approach to overcoming multidrug-resistant bacteria-induced infection from sepsis patients and paves a new avenue on employing nanoparticle-loaded cells for combating inflammation-related infection.展开更多
The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorat...The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.展开更多
The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here...The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.展开更多
This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA comple...This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.展开更多
Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, w...Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, we constructed a hyaluronidase-activated "on-demand" delivery nanocarrier to encapsulate plant essential oils (PEOs) for the synergistic treatment of mulfidrug-resistant bacteria. The bioavailability and selectivity of PEOs was enhanced and the antibacterial effect was significantly improved by combining with the photothermal effect of the nanocarrier. This antibacterial system was successfully applied for healing methicillin-resistant Staphylococcus aureus-infected wound with negligible cytotoxicity and biotoxicity in mice. Given the increasing risk of antibiotic resistance, we believe that this phytochemical-encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.展开更多
Antibacterial nanomaterials have attracted growing interest for bacterial infection therapy.However,most nanomaterials eliminate bacteria either physically or chemically,which hampers their efficacy when dealing with ...Antibacterial nanomaterials have attracted growing interest for bacterial infection therapy.However,most nanomaterials eliminate bacteria either physically or chemically,which hampers their efficacy when dealing with multidrug-resistant bacteria.To overcome this,we integrated copper sulfide(CuS)nanoparticles with active graphene oxide nanosheets(GO NSs)to synthesize a superior nanocomposite(CuS/GO NC)that acts both physically and chemically on the bacteria.CuS/GO NC was produced using a facile hydrothermal method,whereby the CuS nanoparticles grew and were uniformly dispersed on the GO NSs in situ.We found that the CuS/GO NC possesses a unique needle-like morphology that physically damages the bacterial cell membrane.CuS/GO NC also exhibits high oxidase-and peroxidase-like activity,ensuring efficient generation of the reactive oxygen species•OH from H2O2,which kills bacteria chemically.These features endow the CuS/GO NC with excellent antibacterial capabilities to kill multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus(MRSA)with only a single dose.Additionally,it was found that the CuS/GO NC accelerated the healing of infected wounds in vivo owing to its good biocompatibility as well as facilitation of cell migration and collagen secretion.This study provides a new strategy to combine the physical and chemical antibacterial modes of nanomaterials to develop more effective therapies to combat multidrug-resistant bacterial infections.展开更多
Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim o...Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increasing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations (MIC) testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection (ATCC) control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and gradually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.展开更多
Chilled chicken is inevitably contaminated by microorganisms during slaughtering and processing,resulting in spoilage.Cutting parts of chilled chicken,especially wings,feet,and other skin-on products,are abundant in c...Chilled chicken is inevitably contaminated by microorganisms during slaughtering and processing,resulting in spoilage.Cutting parts of chilled chicken,especially wings,feet,and other skin-on products,are abundant in collagen,which may be the primary target for degradation by spoilage microorganisms.In this work,a total of 17 isolates of spoilage bacteria that could secrete both collagenase and lipase were determined by raw-chicken juice agar(RJA)method,and the results showed that 7 strains of Serratia,Aeromonas,and Pseudomonas could significantly decompose the collagen ingredients.The gelatin zymography showed that Serratia liquefaciens(F5)and(G7)had apparent degradation bands around 50 kDa,and Aeromonas veronii(G8)and Aeromonas salmonicida(H8)had a band around.65 and 95 kDa,respectively.The lipase and collagenase activities were detected isolate-by-isolate,with F5 showing the highest collagenase activity.For spoilage ability on meat in situ,F5 performed strongest in spoilage ability,indicated by the total viable counts,total volatile basic nitrogen content,sensory scores,lipase,and collagenase activity.This study provides a theoretical basis for spoilage heterogeneity of strains with high-producing collagenase in meat.展开更多
Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing anti...Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics.Here,we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles(ICG-Ga NPs)containing clinically approved gallium(Ⅲ)(Ga^(3+))and liver targeting indocyanine green(ICG)molecules to eradicate multi-drug resistant(MDR)bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking.The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane,further boost the endocytosis of Ga^(3+),then replace iron in bacteria cells to disrupt bacterial iron metabolism,and demonstrate the synergetic bacterial killing and biofilm disrupting effects.The ICG-Ga NPs show an excellent therapeutic effect against extended spectrumβ-lactamases Escherichia coli(ESBL E.coli)and significantly improve treatment outcomes in infected liver abscess and keratitis.Meanwhile,the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route,guaranteeing the biocompatibility.The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.展开更多
BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate i...BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.展开更多
Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,med...Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.展开更多
Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific micr...Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.展开更多
文摘BACKGROUND The survival of microorganisms on textiles and specifically on healthcare profes-sionals’(HCP)attire has been demonstrated in several studies.The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients.AIM To evaluate the presence,survival and transmission of different multidrug-resistant bacteria(MDRB)from HCP attire onto skin.METHODS Three MDRB[methicillin-resistant Staphylococcus aureus(MRSA);vancomycin-resistant Enterococcus faecium(VRE);carbapenem-resistant Klebsiella pneumoniae,(CRKP)]were inoculated on textiles from scrubs(60%cotton-40%polyester)and white coat(100%cotton)at concentrations of 108 colony-forming units(CFU),105 CFU,and 103 CFU per mL.The inoculation of swatches was divided in time intervals of 1 min,5 min,15 min,30 min,1 h,2 h,3 h,4 h,5 h,and 6 h.At the end of each period,textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media.Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations,for the whole length of the 6-h experiment.RESULTS MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study.VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h,while showing no growth at 103 CFU/mL.CRKP was recovered from 108 CFU/mL for 6 h,up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL.CONCLUSION Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations.The fact that all MDRB can be sustained and transferred to skin even at lower concentrations,supports that textiles are implicated as vectors of bacterial spread.
文摘AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis.METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm<sup>3</sup>. In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed.RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011).CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.
文摘Objective:To investigate the status of multidrug-resistant bacteria and the prevention and control measures of nosocomial in-fection in our hospital.Methods:The annual monitoring of multidrug-resistant bacteria infection was measured to summarize the bacteria species,statistical distribution and antibiotic resistance.Identification of multidrug-resistant bacteria infection in patients infected or hospital acquired infections was taken to analyze the reasons of multidrug-resistant bacteria strain and put forward the relevant measures.Results:The top five of multidrug-resistant strains infections were:Gram-positive bacteria including methicillin-resistant Staphylococcus aureus,Staphylococcus aureus;Gram-negative bacteria including Escherichia coli,Acinetobacter bauman-nii,Klebsiella pneumoniae.Conclusions:The occurrence of multidrug-resistant hospital infections could be prevented by rational use of antibiotics,hand hygiene and disinfection management,and reinforced monitoring of multidrug-resistant bacteria.
基金supported by the Laboratory of Lingnan Modern Agriculture Project(NT2021006)State Key Laboratory of Veterinary Biotechnology Foundation(SKLVBF202102)。
文摘Antibiotic treatment failure against life-threatening bacterial pathogens is typically caused by the rapid emergence and dissemination of antibiotic resistance.The current lack of antibiotic discovery and development urgently calls for new strategies to combat multidrug-resistant(MDR)bacteria,especially those that survive in host cells.Functional nanoparticles are promising intracellular drug delivery systems whose advantages include their high biocompatibility and tunable surface modifications.Inspired by the fact that the rigidity of nanoparticles potentiates their cellular uptake,rigidity-functionalized nanoparticles(RFNs)coated with bacteria-responsive phospholipids were fabricated to boost endocytosis,resulting in the increased accumulation of intracellular antibiotics.Precise delivery and high antibacterial efficacy were demonstrated by the clearing of 99%of MDR bacteria in 4 h using methicillin-resistant Staphylococcus aureus(MRSA)and pathogenic Bacillus cereus as models.In addition,the subcellular distribution of the RFNs was modulated by altering the phospholipid composition on the surface,thereby adjusting the electrostatic effects and reprograming the intracellular behavior of the RFNs by causing them to accurately target lysosomes.Finally,the RFNs showed high efficacy against MRSA-associated infections in animal models of wound healing and bacteremia.These findings provide a controllable rigidity-regulated delivery platform with responsive properties for precisely reprograming the accumulation of cytosolic antibiotics,shedding light on precision antimicrobial therapeutics against intracellular bacterial pathogens in the future.
基金Supported by Philippine Council for Health Research and Development of the Department of Science and Technology(Grant No.2015PHD1)
文摘Objective: To investigate the antibacterial activities of crude ethanol extracts of 12 Philippine medicinal plants.Methods: Crude ethanol extracts from 12 Philippine medicinal plants were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus, extended spectrum β-lactamase-producing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing Pseudomonas aeruginosa and Acinetobacter baumannii. Results: The leaf extracts of Psidium guajava, Phyllanthus niruri, Ehretia microphylla and Piper betle(P. betle) showed antibacterial activity against the Gram-positive methicillinresistant Staphylococcus aureus and vancomycin-resistant Enterococcus. P. betle showed the highest antibacterial activity for these bacteria in the disk diffusion(16-33 mm inhibition diameter), minimum inhibitory concentration(19-156 μg/m L) and minimum bactericidal concentration(312 μg/m L) assays. P. betle leaf extracts only showed remarkable antibacterial activity for all the Gram-negative multidrug-resistant bacteria(extended spectrum β-lactamaseproducing, carbapenem-resistant Enterobacteriaceae and metallo-β-lactamase-producing) in the disk diffusion(17-21 mm inhibition diameter), minimum inhibitory concentration(312-625 μg/m L) and minimum bactericidal concentration(312-625 μg/m L) assays. Conclusions: P. betle had the greatest potential value against both Gram-negative and Grampositive multidrug-resistant bacteria. Favorable antagonistic activities were also exhibited by the ethanol extracts of Psidium guajava, Phyllanthus niruri and Ehretia microphylla.
文摘The study investigated the antibacterial activity of essential oil from the peel of Citrus aurantifolia against eleven multidrug-resistant (MDR) bacterial isolates of clinical origin. The Kirby-Bauer disc diffusion method was used to determine the antibiotic resistance profile of the isolates. Essential oil (EO) from the peels of lime purchased at a market in Ile-Ife was extracted by the hydro-distillation method, while the sensitivity of the isolates to EO was done via agar well diffusion method. The minimum inhibitory and minimum bactericidal concentrations (MIC and MBC) of the EO against the tested isolates were determined following standard methods. All the tested isolates exhibited multidrug resistance (MDR) characteristics. The multiple antibiotics resistant indexes (MARI%) for Gram-positive bacterial isolates ranged between 70% and 100% while that of Gram-negative was 100%. The yield of EO was 1% and the EO demonstrated activities at 25%, 50% and 100% v/v against the MDR bacterial isolates. The activity of EO was mostly not significantly different at the same concentration for all the isolates, and at different concentrations for each of the isolates. The MIC range for Gram-negative and Gram-positive isolates was between 0.195% to 3.125% v/v and 0.39% to 3.125% respectively while the range was between 1.563% to 3.125% and 0.781% to 6.250% v/v for MBC respectively. The study showed that EO from the peel of lime fruits demonstrated excellent in vitro antibacterial activity against MDR bacterial isolates. This potential can be further explored as an alternative for the treatment and management of infections caused by MDR bacterial isolates.
文摘Objective:To investigate the influencing factors of multi-drug resistant bacterial infections in patients with severe disease and establish a predictive model.Methods:207 infected patients in our hospital from 2018 to May 2020 were selected for the study,of which 73 carried drug-resistant bacteria.Results:The risk factor network of people infected with multidrug resistant bacteria is higher than that of people infected with non-multidrug resistant bacteria,and the interaction between risk factors of the former is stronger.Conclusion:Antibiotics must be used appropriately after surgery.When the elderly was abnormal in indicators such as fever and procalcitonin in the ward,they should be considered as high-risk groups of MDRO infection.They need special care and preventive measures.
基金financially supported by the National Natural Science Foundation of China(Nos.82125022,82072383,31800833,21977081,52173135 and 22207024)Zhejiang Provincial Natural Science of Foundation of China(No.LZ19H180001)+1 种基金Wenzhou Medical University(No.KYYW201901)University of Chinese Academy of Science(Nos.WIBEZD2017001-03 and WIUCASYJ2020001)。
文摘Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation ofπ-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O_(2)^(·-))and hydroxyl radical(·OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar concentration under a low white light irradiation(30 mW/cm^(2)).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-I photodynamic therapy(PDT)performance for efficient antibacterial treatments,advancing the development of antibacterial agents.
基金National Natural Science Foundation of China,Grant/Award Numbers:52002133,U1609219,81871482Foundation for Basic and Applied Basic Research of Guangdong Province,Grant/Award Number:2019A1515110328+1 种基金NSFC Development of National Major Scientific Research Instrument,Grant/Award Number:61927816Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program,Grant/Award Number:2017BT01X137。
文摘Sepsis,caused by uncontrollable infection and inflammatory response,leads to more than 30 million infected patients and results in high morbidity worldwide every year.Currently,no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm.Here,we report macrophages loaded with aggregated carbon dots(ACDs)in the lysosome,termed MCDs,to treat sepsis in immunosuppressive mice.The ACDs are constructed by negative CDs and amine-abundant polyethyleneimine(PEI),enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy.The ACDs are specifically located in the macrophage lysosomes,efficiently enhancing the multidrug-resistant bacteria-killing ability of MCDs.More importantly,the MCDs possess superior anti-inflammatory effects such as reducing the number of pro-inflammatory(M1)and stimulating anti-inflammatory(M2)macrophages.These effects upregulate the inflammatory cytokines(TNF-α,IL-1β,IL-4,and IL-10),ultimately resulting in increased sepsis survival.Our work provides an intelligent approach to overcoming multidrug-resistant bacteria-induced infection from sepsis patients and paves a new avenue on employing nanoparticle-loaded cells for combating inflammation-related infection.
基金This work is supported by the National Natural Science Foundation of China(Nos.51802192,81802156,and 81772338)the Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2017ZD05)+2 种基金Natural Science Foundation of Shanghai(No.19ZR1474800)Shanghai Sailing Program(No.18YF1410700)Innovation Research Plan supported by Shanghai Municipal Education Commission(No.ZXWF082101).
文摘The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies.Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysiltyl)propyl]ethylene diamine(TSD)-mediated method(SWCNTs@mSiO2-TSD@Ag).In this system,the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs,which will increase their contact area with bacteria cell walls.Meanwhile,the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution,which induces an enhanced antibacterial activity.Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes(SWCNTs@mSiO2-TSD)and commercialAg NPs,this combination nanosystem of SWCNTs@mSiO2-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli(E.coli)and Staphylococcus aureus(S.aureus)in vitro through damaging the bacterial cell membranes and a fast release of silver ions.Furthermore,the in vivo rat skin infection model verifies that SWCNTS@mSiO2-TSD@Ag have remarkably improved abilities of bacterial clearance,wound healing promoting as well as outstanding biocompatibility.Therefore,this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.
基金supported by the National Key R&D Program of China(2021YFB3800900)the National Natural Science Foundation of China(22122501,21875014 and 52073013)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910010024)。
文摘The abuse of antibiotics in treating microbial infections has led to the emergence and prevalence of drugresistant bacteria.Thus,the development of novel antibacterial materials is attracting increasing attention.Here,a series of flexible electrostatic hydrogels with excellent antibacterial ability were constructed using a mixture of nitric oxide(NO)-releasing nitrated chitosan(CSNO)and mesotetra(4-carboxyphenyl)porphine(TCPP)with salmon sperm DNA(ssDNA)solution.When cultured with gram-negative bacteria under solar simulator irradiation,TCPP-CSNO_(m)ssDNA_(n) hydrogels released reactive oxygen species(ROS)and NO to produce peroxynitrite ions(ONOO^(−)).ONOO−is efficient at killing bacteria,thereby improving the antimicrobial ability of photodynamic therapy against gram-negative bacteria.The hydrogels exhibited powerful antibacterial activity in vivo when used to treat skin infections caused by drugresistant bacteria,making them a promising candidate for clinical applications.A string of antibacterial hydrogels that release ROS and NO synergistically can bring new possibilities for effectively killing drug-resistant bacteria and be of great value in anti-infection wound dressings and other applications.
基金supported by the start-up funding from Nankai University(to C.Z.)the National Natural Science Foundation of China(nos.52003123,21620102005,and 81722026)the CAMS Innovation Fund for Medical Sciences(no.2016-I2M-3-022).
文摘This study reports the fabrication of a novel photothermal material formed via the physical blending of excess lauric acid(LA)and cupric acetate,followed by efficient ligand exchange.Surprisingly,the copper–LA complex exhibited a 12-fold enhancement of the molar extinction coefficient in the nearinfrared(NIR)region relative to aqueous cupric acetate.Inspired by this interesting finding,we formulated these photothermal materials into colloidally dispersed nanoparticles via a technique that combined nanoprecipitation and in situ surface polymerization for antibacterial studies.The resultant nanoparticles exhibited rapid and stable photothermal responses to NIR irradiation,with a 4-fold enhanced photothermal conversion efficiency relative to aqueous cupric acetate.Since a positively charged monomer was incorporated during in situ surface polymerization,these positively charged nanoparticles were ingested efficiently and subsequently digested by drug-resistant bacteria.By combining the LA-mediated membrane-damaging effect,copper-mediated Fenton-like reaction,as well as the photothermal effect of the copper–LA complex,a broad-spectrum,multimodal,and synergistic antibacterial effect was achieved both in vitro and in vivo,with the killing efficiency up to 99.99%for ampicillin-resistant Escherichia coli(Ampr E.coli)and 99.9999%for methicillinresistant Staphylococcus aureus(MRSA).Our newly developed nanobiocide represents a class of exceptional broad-spectrum antibacterial materials,holding great potential for treating drug-resistant infections in clinical settings.
基金support from the National Natural Science Foundation of China (Nos. 21210002, 21431007, 21533008, 21403209, 21601175, and 21673223) and the Jilin Province Science and Technology Develop- ment Plan Project (No. 20140101039JC).
文摘Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, we constructed a hyaluronidase-activated "on-demand" delivery nanocarrier to encapsulate plant essential oils (PEOs) for the synergistic treatment of mulfidrug-resistant bacteria. The bioavailability and selectivity of PEOs was enhanced and the antibacterial effect was significantly improved by combining with the photothermal effect of the nanocarrier. This antibacterial system was successfully applied for healing methicillin-resistant Staphylococcus aureus-infected wound with negligible cytotoxicity and biotoxicity in mice. Given the increasing risk of antibiotic resistance, we believe that this phytochemical-encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.
基金This study was supported by the National Natural Science Foundation of China(Nos.81972080 and 81902198)China Postdoctoral Science Foundation(Nos.2018M640776,2019M662980,and BX20190150)+5 种基金Natural Science Foundation of Guangdong Province(Nos.2015A30312004 and 2020A1515010398)Science and Technology Planning Project of Guangdong Province(Nos.2014A020215025 and 2017B030314139)Medical Research Foundation of Guangdong Province(A2019228)Research Program of PLA(No.CGZ16C004)President Foundation of Zhujiang Hospital,Southern Medical University(No.yzjj2018rc09)Scientific Research Foundation of Southern Medical University(Nos.C1051353 and PY2018N060).
文摘Antibacterial nanomaterials have attracted growing interest for bacterial infection therapy.However,most nanomaterials eliminate bacteria either physically or chemically,which hampers their efficacy when dealing with multidrug-resistant bacteria.To overcome this,we integrated copper sulfide(CuS)nanoparticles with active graphene oxide nanosheets(GO NSs)to synthesize a superior nanocomposite(CuS/GO NC)that acts both physically and chemically on the bacteria.CuS/GO NC was produced using a facile hydrothermal method,whereby the CuS nanoparticles grew and were uniformly dispersed on the GO NSs in situ.We found that the CuS/GO NC possesses a unique needle-like morphology that physically damages the bacterial cell membrane.CuS/GO NC also exhibits high oxidase-and peroxidase-like activity,ensuring efficient generation of the reactive oxygen species•OH from H2O2,which kills bacteria chemically.These features endow the CuS/GO NC with excellent antibacterial capabilities to kill multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus(MRSA)with only a single dose.Additionally,it was found that the CuS/GO NC accelerated the healing of infected wounds in vivo owing to its good biocompatibility as well as facilitation of cell migration and collagen secretion.This study provides a new strategy to combine the physical and chemical antibacterial modes of nanomaterials to develop more effective therapies to combat multidrug-resistant bacterial infections.
基金supported by the National Natural Science Foundation of China (21175020)National Key Basic Research Program (2010CB732404)+4 种基金Doctoral Fund of Ministry of Education of China (20090092110028)National High Technology Research and Development Program(2007AA022007)Guangdong Province (2011B090400357)Graduate Research and Innovation Program of Jiangsu Province (CXLX_0145)State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences
文摘Antimicrobial resistance has now become a very serious global public health problem. New drug discovery and development are urgently needed to combat the growing threat of multidrug-resistant (MDR) bacteria. The aim of this study was to explore the potential application of three ferrocene-carborane derivatives as new promising agents to confront the problem of increasing antibiotic resistance. The results of agar diffusion bioassay, minimal inhibitory concentrations (MIC) testing and time-kill assay illustrate their broad-spectrum antimicrobial activities to both American Type Culture Collection (ATCC) control strains and MDR clinical isolates. It is evident that the relevant antimicrobial properties are all in a dose-dependent manner and gradually transform into a bactericidal effect from a bacteriostatic effect with the increasing of the drug concentration. Furthermore, these ferrocene-carborane derivatives have no/little toxic effect on normal cells like HELF cells and lead to little hemolysis at their MICs. This raises the possibility to develop novel antimicrobial drugs using these new ferrocene carborane derivants.
基金financed by grants from the Natural Science Foundation of Jiangsu Province in China (BK20221515)the National Natural Science Foundation of China (32172266)。
文摘Chilled chicken is inevitably contaminated by microorganisms during slaughtering and processing,resulting in spoilage.Cutting parts of chilled chicken,especially wings,feet,and other skin-on products,are abundant in collagen,which may be the primary target for degradation by spoilage microorganisms.In this work,a total of 17 isolates of spoilage bacteria that could secrete both collagenase and lipase were determined by raw-chicken juice agar(RJA)method,and the results showed that 7 strains of Serratia,Aeromonas,and Pseudomonas could significantly decompose the collagen ingredients.The gelatin zymography showed that Serratia liquefaciens(F5)and(G7)had apparent degradation bands around 50 kDa,and Aeromonas veronii(G8)and Aeromonas salmonicida(H8)had a band around.65 and 95 kDa,respectively.The lipase and collagenase activities were detected isolate-by-isolate,with F5 showing the highest collagenase activity.For spoilage ability on meat in situ,F5 performed strongest in spoilage ability,indicated by the total viable counts,total volatile basic nitrogen content,sensory scores,lipase,and collagenase activity.This study provides a theoretical basis for spoilage heterogeneity of strains with high-producing collagenase in meat.
基金the National Natural Science Foundation of China(No.81971667 and 81671748 and)the Key Research and Development Projection of Zhejiang Province(No.2020C03035).
文摘Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics.Here,we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles(ICG-Ga NPs)containing clinically approved gallium(Ⅲ)(Ga^(3+))and liver targeting indocyanine green(ICG)molecules to eradicate multi-drug resistant(MDR)bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking.The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane,further boost the endocytosis of Ga^(3+),then replace iron in bacteria cells to disrupt bacterial iron metabolism,and demonstrate the synergetic bacterial killing and biofilm disrupting effects.The ICG-Ga NPs show an excellent therapeutic effect against extended spectrumβ-lactamases Escherichia coli(ESBL E.coli)and significantly improve treatment outcomes in infected liver abscess and keratitis.Meanwhile,the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route,guaranteeing the biocompatibility.The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.
文摘BACKGROUND Multidrug-resistant Gram-negative bacteria,exacerbated by excessive use of antimicrobials and immunosuppressants,are a major health threat.AIM To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia,and to provide theoretical reference for clinical diagnosis and treatment.METHODS This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022.After bacteriological culture,the patients'airway secretions were collected to confirm the presence of Gram-negative bacilli.The patients were divided into the experimental and control groups according to the medication used.The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous,nebulization,or intravenous combined with nebulization,with a daily dosage of 1.5–3.0 million units.The control group consisted of 26 patients who received standard dosages of other antibiotics(including sulbactam sodium for injection,cefoperazone sodium sulbactam for injection,tigecycline,meropenem,or vaborbactam).RESULTS Of the 28 patients included in the research group,26 patients showed improvement,treatment was ineffective for two patients,and one patient died,with the treatment efficacy rate of 92.82%.Of the 26 patients in the control group,18 patients improved,treatment was ineffective for eight patients,and two patients died,with the treatment efficacy rate of 54.9%;significant difference was observed between the two groups(P<0.05).The levels of white blood cell(WBC),procalcitonin(PCT),and C-reactive protein(CRP)in both groups were significantly lower after treatment than before treatment(P<0.05),and the levels of WBC,PCT,and CRP in the research group were significantly lower than those in the control group(P<0.05).Compared with before treatment,there were no significant changes in aspartate aminotransferase,creatinine,and glomerular filtration rate in both groups,while total bilirubin and alanine aminotransferase decreased after treatment(P<0.05)with no difference between the groups.In patients with good clinical outcomes,the sequential organ failure assessment(SOFA)score was low when treated with inhaled polymyxin sulfate,and specific antibiotic treatment did not improve the outcome.Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes.CONCLUSION Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable.Moreover,the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions,providing new ideas for clinical administration.
基金Science and Technology Projects in Key Fields of Traditional Chinese Medicine in Tianjin(No.2021010)Discipline Development Fund of First Teaching Hospital of Tianjin University of Traditional Chinese Medicine(No.XKJJ201734)。
文摘Objective:To establish extensively drug-resistant Pseudomonas aeruginosa(XDR-PA)infection-induced pneumonia model in rats.Methods:Twenty-four male SD rats were randomly divided into blank group,low bacterial group,medium bacterial group,and high bacterial group.The low,medium and high bacterial groups were given intratracheal instillation of 0.1 mL of bacterial suspension(bacterial concentration in turn is 7.5×10^(9),3×10^(10),6×10^(10)CFU/mL),while the blank group were given the same volume of sterile normal saline.After modeling,the general conditions of rats in each group were observed,including mental state,hair,respiration,activity,eating,weight,and the survival curve was drawn.The pathological characteristics of lung tissue and the infiltration of inflammatory cells were observed.Pathogenic identification of each group was carried out by bacterial culture of lung tissue homogenate.Results:The general state of the blank group was normal,and the rats in other groups showed signs of mental depression,bristling,shortness of breath,even oral and nasal bleeding,decreased food intake and activity,and significant weight loss,and different degrees of death within 48 hours,the difference was statistically significant(P<0.05).Pathological results showed that the alveolar structure of rats in the blank group was complete,and the alveolar space was clear without exudation.The lung tissue of the low and medium bacterial groups showed obvious inflammatory cell infiltration,alveolar structure destruction,alveolar septum thickening,interstitial edema,but the pathological damage of the medium group was more severe,with a mortality rate of up to 50%,and the mortality rate of the low bacterial group was 17%.In the high bacterial group,red blood cells,inflammatory cells and a large amount of fibrin-like exudation can be seen in the alveolar space,which has the pathological characteristics of acute respiratory failure,and the mortality rate is as high as 67%.The results of bacterial culture of lung tissue homogenate showed that the blank group had no bacterial colonies,while PA colony growth can be seen in low,medium and high bacterial groups.Conclusion:9 Intratracheal instillation of low bacterial count(0.1 mL of 7.5×10^(9) CFU/mL)XDR-PA bacterial suspension can successfully construct a rat pneumonia model of XDR-PA infection.
基金funded by the National Science Centre,Poland(Project No.:2017/26/D/NZ6/00136).
文摘Pathogenic microorganisms produce numerous metabolites,including volatile organic compounds(VOCs).Monitoring these metabolites in biological matrices(e.g.,urine,blood,or breath)can reveal the presence of specific microorganisms,enabling the early diagnosis of infections and the timely implementation of tar-geted therapy.However,complex matrices only contain trace levels of VOCs,and their constituent com-ponents can hinder determination of these compounds.Therefore,modern analytical techniques enabling the non-invasive identification and precise quantification of microbial VOCs are needed.In this paper,we discuss bacterial VOC analysis under in vitro conditions,in animal models and disease diagnosis in humans,including techniques for offline and online analysis in clinical settings.We also consider the advantages and limitations of novel microextraction techniques used to prepare biological samples for VOC analysis,in addition to reviewing current clinical studies on bacterial volatilomes that address inter-species in-teractions,the kinetics of VOC metabolism,and species-and drug-resistance specificity.