BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safel...BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safely while avoiding many hospital-acquired complications.This is a major boost or low-hanging fruit intervention in antimicrobial stewardship practices with multiple targets like decreasing hospital stays,its related complications,the economy,the burden on hospitals,etc.However,resource-constrained countries like India practices rarely OPAT in an evidence-based way.AIM To evaluate the effectiveness,safety,and feasibility along with barriers and facilitators of OPAT practices in resource-poor settings,with a focus on its role in antimicrobial stewardship.METHODS This pilot longitudinal observational study included patients who met OPAT checklist criteria and were committed to post-discharge follow-up.Pre-discharge education and counselling were provided,and demographic data were recorded.Various outcome measures,including barriers and facilitators,were identified through an extensive literature review,fishbone diagram preparation,data collection and analysis,and patient feedback.All healthcare workers who were taking care of the patients discharged with OPAT were contacted with openended questions to get data on feasibility.The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences,Rishikesh.We used descriptive analysis and theχ2 test to analyze data.P value<0.05 was considered significant.RESULTS Out of 20 patients,the mean age was 37 years.The cohort comprised 13 males.OPAT was administered at home in 15 cases and at nursing homes in 5 cases,with nine patients receiving treatment from family members and 11 patients receiving care from a local nurse.The infections requiring OPAT included:Kidney-urinary tract(6 cases),gastrointestinal tract(4 cases),respiratory tract(4 cases),meningitis(3 cases),endocarditis(2 cases),and multiple visceral abscesses(1 case).Nineteen out of 20 patients achieved afebrile status.Half of the patients did not receive education,counselling,or demonstrations prior to discharge,but all patients rated the service as good/excellent.According to doctors’feedback,OPAT is highly beneficial and effective for patients when systematically implemented with daily telephonic monitoring,but faces challenges due to the lack of standardized protocols,dedicated teams,and adequate resources.The implementation of OPAT resulted in a reduction of hospitalization duration by an average of two weeks.CONCLUSION This pilot study proves that OPAT is safe,feasible,and efficacious by reducing two weeks of hospitalization in resource-poor settings.OPAT contributes directly to antimicrobial stewardship by reducing hospital stays and hospital-acquired complications,which is vital in combating antimicrobial resistance(AMR)and aligns with the global action plan for AMR in infection prevention and optimal antimicrobial utilization.展开更多
Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucro...Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.展开更多
The main objective of this study is to evaluate the antibacterial effect of antibacterial pho-todynamic therapy(aPDT)on Streptococcus mutans(S.mutans)biofilm model in vitro.The selection of photosensitizers is the key...The main objective of this study is to evaluate the antibacterial effect of antibacterial pho-todynamic therapy(aPDT)on Streptococcus mutans(S.mutans)biofilm model in vitro.The selection of photosensitizers is the key step for the efficacy of photodynamic therapy(PDT).However,no studies have been conducted in the oral field to compare the functional char-acteristics and application effects of PDT mediated by various photosensitizers.In this re-search,the antibacterial effect of Methylene blue(MB)/650 nm laser and Hematoporphyrin monomethyl ether(HMME)/532 nm laser on S.mutans biofilm was compared under different energy densities to provide experimental reference for the clinical application of the two PDT.The yield of lactic acid was analyzed by Colony forming unit(CFU)and spectrophotometry,and the complete biofilm activity was measured by Confocal Laser Scanning Microscopy(CLSM)to evaluate the bactericidal effect on each group.Based on the results of CFU,the bacterial colonies formed by 30.4J/cm^(2)532nm MB-aPDT group and 30.4J/cm^(2)532nm HMME-aPDT group were significantly less than those in other groups,and the bacterial colonies in HMME-aPDT group were less than those in HMME-aPDT group.Lactic acid production in all treatment groups except the photosensitizer group was statistically lower than that in the normal saline control group.The activity of bacterial plaque biofilm was significantly decreased in the two groups treated with 30.4 J/cm^(2) aPDT.Therefore,aPDT suitable for energy measurement can kill S.mutans plaque biofilm,and MB-aPDT is better than HMME-aPDT.展开更多
Antibiotic administration is the mainstay for treating bacterial infections,but multidrug-resistant(MDR)bacteria jeopardize its effectiveness.Antimicrobial photodynamic therapy(aPDT)offers a promising strategy with le...Antibiotic administration is the mainstay for treating bacterial infections,but multidrug-resistant(MDR)bacteria jeopardize its effectiveness.Antimicrobial photodynamic therapy(aPDT)offers a promising strategy with less risk of inducing resistance,yet the lack of a suitable wearable light source limits its widespread adoption.Here,we design flexible quantum dot light-emitting diodes(F-QLEDs)for effective aPDT treatment of MDR bacteria.By simultaneous optical,thermal,and reliability management,we achieved F-QLEDs with emission spectrum matching the photosensitizer absorption,physiologically safe surface temperature(<41℃),enhanced operating lifetime(7.5X),and ambient shelf life>1 month.Subsequently,aPDT testing demonstrated a~9-log reduction of Staphylococcus aureus and~2-3 log reduction of Pseudomonas aeruginosa compared to controls.Additionally,testing with different photosensitizers confirmed F-QLED versatility for targeted aPDT.These results showcase the potent antimicrobial efficacy of F-QLEDs and their potential as wearable optical platforms for point-of-care treatment of MDR infections and broader photomedical applications.展开更多
Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found i...Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.展开更多
Dental caries （tooth decay） is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineraI in tooth structure. Killing cariogenic b...Dental caries （tooth decay） is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineraI in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound （Glycyrrhizol A）, from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to produce these specific herbal extracts in large quantities, and then used these extracts to develop a sugar-free lollipop that effectively kills cariogenic bacteria like Streptococcus mutans. Further studies showed that these sugar-free lollipops are safe and their antimicrobial activity is stable. Two pilot human studies indicate that a brief application of these lollipops （twice a day for ten days） led to a marked reduction of cariogenic bacteria in oral cavity among most human subjects tested. This herbal lollipop could be a novel tool to promote oral health through functional foods.展开更多
The most common cause of admission to the Pediatric Dentistry service is dental pain, active deafness and an oppressive sensation that is sometimes<span> throbbing and burning. Pharmacotherapy in Pediatric ...The most common cause of admission to the Pediatric Dentistry service is dental pain, active deafness and an oppressive sensation that is sometimes<span> throbbing and burning. Pharmacotherapy in Pediatric Dentistry must be effective, safe, and rational in neonates, infants, and children. The pharmacotherapeutic follow-up of pediatric patients from Integral Clinic of the Odontopediatric Specialty</span><span> </span><span>(CLIO) and Kindergarten Clinic (CLIJANI), Autonom</span><span>ous University of Zacatecas</span><span> </span><span>(UAZ) was carried out. Through an observa</span><span>tion</span><span>al, exploratory, and cross-sectional study, 23 patients from the Pediatric Dentistry Specialty Clinic (CLIO/UAO/UAZ) and 35 clinical records of patients </span><span>from CLIJANI, from August 2019-2020, were analyzed.</span><span> </span><span>Prior authorization</span><span> for </span><span>the patient, an interview, and pharmacotherapeutic follow-up were per</span><span>formed, recording data on the indicated drug, the dose, and the schedule of use.</span><span> </span><span>On carrying out the interview on pharmacotherapy with the parents or guardians who accompany the patient, 91.3% of the pediatric patients were not administered pharmacological treatment. It was observed that there is no adequate adherence to the pharmacological treatment in pediatric patients</span><span>.</span>展开更多
Sepsis,defined as life-threatening organ dysfunction caused by a dysregulated host response to infection,remains a major challenge in critical care and a leading cause of mortality worldwide.Early,appropriate antibiot...Sepsis,defined as life-threatening organ dysfunction caused by a dysregulated host response to infection,remains a major challenge in critical care and a leading cause of mortality worldwide.Early,appropriate antibiotic administration is among the most effective strategies to improve outcomes,making optimization of antimicrobial therapy a priority.Optimal antibiotic therapy is the careful selection of the agent and dosing regimen that optimizes outcomes while minimizing adverse effects and antimicrobial resistance.Yet,paradoxically,dosing regimens in sepsis often rely on standardized protocols that overlook fundamental biological variables such as sex and gender,as well as intersecting factors like socioeconomic status,ethnicity,and access to care.[1]This omission compromises efficacy and perpetuates clinical inequalities.展开更多
The single-function agents with wide-spectrum activity which tend to disturb the ecological balance of oral cavity cannot satisfy dental treatment need.A multi-functional agent with specifically targeted killing prope...The single-function agents with wide-spectrum activity which tend to disturb the ecological balance of oral cavity cannot satisfy dental treatment need.A multi-functional agent with specifically targeted killing property and in situ remineralization is warranted for caries management.A novel multi-functional agent(8DSS-C8-P-113)consisting of three domains,i.e.,a non-specific antimicrobial peptide(AMP)(P-113),a competence stim-ulating peptide(C8),and an enhancing remineralization domain(8DSS),is fabricated and evaluated in this study.The findings demonstrates that 2μM mL^(-1)of 8DSS-C8-P-113 eliminates planktonic Streptococcus mutans(S.mutans)without disrupting the oral normal flora.At a concentration of 8μM mL^(-1),it exhibits the ability to prevent S.mutans’adhesion.Furthermore,8DSS-C8-P-113 self-assembles a hydrogel state at the higher con-centration of 16μM mL^(-1).This hydrogel self-adheres on the tooth surface,resisting acid attack,eradicating S.mutans’biofilm,and inducing mineralization in order to facilitate the repair of demineralized dental hard tissue.Its significant effectiveness in reducing the severity of dental caries is also demonstrated in vivo in a rat model.This study suggests that the multi-functional bioactive AMP 8DSS-C8-P-113 is a promising agent to specifically target pathogen,prevent tooth demineralization,and effectively induce in situ bio-mimic reminer-alization for the management of dental caries.展开更多
Periodontitis is a prevalent chronic inflammatory disease driven by biofilms formed by common oral pathogens,leading to the progressive destruction of periodontal tissues.However,conventional antimicrobial therapies o...Periodontitis is a prevalent chronic inflammatory disease driven by biofilms formed by common oral pathogens,leading to the progressive destruction of periodontal tissues.However,conventional antimicrobial therapies often neglect the clearance of bacterial endotoxins such as lipopolysaccharide(LPS),a potent pro-inflammatory mediator that exacerbates tissue inflammation.To address this problem,we developed a multifunctional nanoreactor featuring both antibacterial and LPS-scavenging capabilities.Utilizing a photochemical synthesis strategy,Ag-TiO_(2) nanoparticles with diameters below 10 nm were grown in situ onto micro-scale carriers 13X zeolite and activated carbon(AC).The 13X matrix enhances photocatalytic oxidative activity,while AC offers a high specific surface area for the adsorption of LPS and hydrogen sulfide(H2S).The Ag-TiO_(2) photocatalyst further endows the system with self-cleaning ability and improved degradation efficiency of harmful agents.Under 405 nm blue light emitting diode(LED)light irradiation,the composite efficiently generates reactive oxygen species(ROS),achieving>98% bactericidal rates against Actinobacillus Actinomycetemcomitans(A.actinomycetemcomitans),Streptococcus mutans(S.mutans),and Porphyromonas gingivalis(P.gingivalis),with up to 80% biofilm removal.Additionally,AC-Ag-TiO_(2) effectively adsorbs and degrades LPS,significantly reducing the secretion of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in macrophages.In a mouse model of periodontitis,the material not only stabilized the oral microbiota but also promoted periodontal tissue repair.Taken together,this study introduces a multi-scale catalytic platform that synergistically combines photocatalysis and adsorption to achieve dual antibacterial and anti-inflammatory effects,offering a highly efficient and long-lasting therapeutic strategy for periodontitis.展开更多
Cationic compounds with quaternary ammonium structures are one of the most commonly utilized antibacterial materials,which can effectively overcome the emergence of bacterial drug resistance.Systematic investigation o...Cationic compounds with quaternary ammonium structures are one of the most commonly utilized antibacterial materials,which can effectively overcome the emergence of bacterial drug resistance.Systematic investigation on the structure-activity relationship of such cationic compounds is essential for the development of efficient antimicrobials toward different bacterial strains with clear antimicrobial mechanisms.In this study,we rationally designed and synthesized two quaternary ammonium photosensitizers with aggregation-induced emission(AIE)properties.One possesses a unilaterally charged and Janus-type structure with two positively charged moieties at one tail and two hydrophobic alkyl chains on the other side.The other is a bilaterally symmetric molecule bearing quaternary ammonium structures at both ends.The fluorescence staining experiments,bactericidal assays,and bacterial morphology analyses reveal that the Janus-type AIE luminogen show superior photodynamic antimicrobial activities possibly due to its better disruption of the bacterial membranes.Further theoretical study on the molecule-membrane interaction and molecular dynamics gains deeper insights into the intrinsic relationships between molecular structures and antibacterial activities,which provides a feasible design strategy for high-performance antimicrobial agents.展开更多
Bacterial infection is currently a serious challenge globally, causing death of thousands of human beings. New antimicrobial agents with novel mechanism of action are urgently needed. Transition metal complexes have s...Bacterial infection is currently a serious challenge globally, causing death of thousands of human beings. New antimicrobial agents with novel mechanism of action are urgently needed. Transition metal complexes have shown great potentials in photodynamic and photocatalytic therapy. Herein, we take full advantage of metal photocatalyst and successfully developed a novel cyclometalated iridium(Ⅲ) complex(Ir1) with higher biofilm damage efficiency than the clinical antibiotics. Ir1 synergistically generates reactive oxygen species and coenzyme photocatalytic activity with high efficiency under white light irradiation. Combined with these properties, Ir1 exhibited excellent photoinactivation of S. aureus and effectively damaged the biofilm. This work provides a new approach for the development of antibacterial photodynamic therapy.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
Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues.Traditional remineralization treatments often have limited efficacy d...Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues.Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity.According to the Interrupting Dental Caries(IDC)theory,ideal caries-preventive materials should possess both antibacterial and remineralizing properties.Furthermore,effective adhesion to dental surfaces is crucial.Inspired by the wet adhesion properties of the salivary acquired pellicle,we developed a multifunctional gargle named Ce6@PDN-SAP(CP-SAP).This formulation employed peptide dendrimer nanogels(PDN)as a carrier for the photosensitizer Ce6,further functionalized with saliva-acquired peptide(SAP)to confer wet adhesion properties.CP-SAP rapidly adhered to the dental surface and remained effective for extended periods.Upon laser irradiation,Ce6 generated reactive oxygen species(ROS),disrupting bacterial outer membrane integrity,causing protein leakage,and reducing ATP levels,thereby achieving potent antibacterial effects.Following this,PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues.In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle.In conclusion,CP-SAP,as an innovative approach grounded in the IDC theory,holds great promise for the prevention and treatment of dental caries.展开更多
Early childhood caries(ECC)is a public healthcare concern that greatly reduces the quality of life of young children.As a leading factor of ECC,cariogenic biofilms are composed of acidogenic/aciduric pathogens and ext...Early childhood caries(ECC)is a public healthcare concern that greatly reduces the quality of life of young children.As a leading factor of ECC,cariogenic biofilms are composed of acidogenic/aciduric pathogens and extracellular polysaccharides(EPSs),creating an acidic and protected microenvironment.Antimicrobial photodynamic therapy(aPDT)is a noninvasive,painless,and efficient therapeutic approach that is suitable for treating ECC.However,due to the hyperfine structure of cariogenic biofilms,most photosensitizers(PSs)could not access and penetrate deeply in biofilms,which dramatically hamper their efficiency in the clinic.Herein,bioresponsive nanoparticle loaded with chlorin e6(MPP-Ce6)is developed,which largely increases the penetration depth(by over 75%)and retention(by over 100%)of PS in the biofilm compared with free Ce6.Furthermore,MPP-Ce6-mediated aPDT not only kills the bacteria in preformed biofilms but also inhibits multispecies biofilm formation.A rampant caries model is established to mimic ECC in vivo,where the population of cariogenic bacteria is decreased to 10%after MPP-Ce6-mediated aPDT.Importantly,the number and severity of carious lesions are efficiently reduced via Keyes’scoring and micro-CT analysis.This simple but effective strategy can serve as a promising approach for daily oral hygiene in preventing ECC.展开更多
Sepsis is defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection.[1]Sepsis was responsible for approximately 20%of deaths worldwide before the corona virus disease pandemi...Sepsis is defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection.[1]Sepsis was responsible for approximately 20%of deaths worldwide before the corona virus disease pandemic and has been characterized as a global health priority by the World Health Organization.[2]Therapy for sepsis is characterized by rapid initiation of antimicrobial therapy,fluid resuscitation,and non-specific supportive care.[3]Antimicrobial therapy is subsequently tailored if an inciting organism is identified or specific organisms are confidently ruled out.International guidelines,such as the Surviving Sepsis Campaign,have been associated with improved outcomes by putting together a compendium of evidence-based recommendations based on GRADE methodology.展开更多
Considering the increasing abundance of antibiotic-resistant bacteria,novel antimicrobial approaches need to be investigated.Photothermal therapy(PTT),an innovative noninvasive therapeutic technique,has demonstrated s...Considering the increasing abundance of antibiotic-resistant bacteria,novel antimicrobial approaches need to be investigated.Photothermal therapy(PTT),an innovative noninvasive therapeutic technique,has demonstrated significant potential in addressing drug-resistant bacteria and bacterial biofilms.However,when used in isolation,PTT requires higher-temperature conditions to effectively eradicate bacteria,thereby potentially harming healthy tissues and inducing new inflammation.This study aims to present a comprehensive review of nanomaterials with intrinsic antimicrobial properties,antimicrobial materials relying on photothermal action,and nanomaterials using drug delivery antimicrobial action,along with their applications in antimicrobials.Additionally,the synergistic mechanisms of these antimicrobial approaches are elucidated.The review provides a reference for developing multifunctional photothermal nanoplatforms for treating bacterially infected wounds.展开更多
Polydimethylsiloxane(PDMS)is widely used in biomedical applications due to its biocompatibility,chemical stability,flexibility,and resistance to degradation in physiological environments.However,its intrinsic inertnes...Polydimethylsiloxane(PDMS)is widely used in biomedical applications due to its biocompatibility,chemical stability,flexibility,and resistance to degradation in physiological environments.However,its intrinsic inertness limits further(bio)functionalization,and its hydrophobic recovery compromises the longevity of conventional surface modifications.To address these challenges,we developed a nanoprecipitation method for the straight-forward colloidal deposition,covalent thermal crosslinking,and surface anchoring of a chemically tunable,biocompatible polyacrylamide with reactive hydroxyl groups,enabling further surface modifications.This polymer incorporates~6%bioinspired catechol units,introduced via an elegant one-pot Kabachnik-Fields re-action,to facilitate thermally induced network formation and enhance adhesion to plasma-activated PDMS.The resulting uniform coatings exhibited tunable dry layer thicknesses up to 44±7 nm and effectively suppressed PDMS chain rearrangement even after steam autoclaving,ensuring long-term stability in aqueous and ambient environments for at least 90 days.The bioactive post-modification potential was demonstrated in a proof-of-concept study by immobilizing the photosensitizer rose bengal at surface concentrations of 20 or 40μg cm^(-2).The coating exhibited antimicrobial activity against S.aureus,achieving a 4-log reduction(99.99%)in colony-forming units after 30 min of irra-diation at 554 nm(342 J cm^(-2)),even when bacteria were suspended in liquid,without direct surface contact.In contrast,antimicrobial activity against E.coli was only observed with minimized liquid volume,bringing the motile bacteria into close contact with the surface.This work established a straightforward and versatile strategy for the stable and bioactive functionalization of PDMS surfaces for application in non-invasive surface decontamination.展开更多
Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic...Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs.The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics.Herein,a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented,encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms.Furthermore,the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy,mainly focusing on skin,bone,periodontal and tendon tissues regeneration and repair,are systematically summarized and discussed.In particular,for the treatment of skin infection wounds,we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs,including(i)single model therapies such as metal ion therapy,chemodynamic therapy,photothermal therapy,and photodynamic therapy;and(ii)multimodel therapies involving arbitrary combinations of these single models.Additionally,the limitations,challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed.We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.展开更多
文摘BACKGROUND Outpatient parenteral antimicrobial therapy(OPAT)offers a crucial method for administering intravenous/intramuscular antimicrobials outside of hospital settings,allowing patients to complete treatment safely while avoiding many hospital-acquired complications.This is a major boost or low-hanging fruit intervention in antimicrobial stewardship practices with multiple targets like decreasing hospital stays,its related complications,the economy,the burden on hospitals,etc.However,resource-constrained countries like India practices rarely OPAT in an evidence-based way.AIM To evaluate the effectiveness,safety,and feasibility along with barriers and facilitators of OPAT practices in resource-poor settings,with a focus on its role in antimicrobial stewardship.METHODS This pilot longitudinal observational study included patients who met OPAT checklist criteria and were committed to post-discharge follow-up.Pre-discharge education and counselling were provided,and demographic data were recorded.Various outcome measures,including barriers and facilitators,were identified through an extensive literature review,fishbone diagram preparation,data collection and analysis,and patient feedback.All healthcare workers who were taking care of the patients discharged with OPAT were contacted with openended questions to get data on feasibility.The study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences,Rishikesh.We used descriptive analysis and theχ2 test to analyze data.P value<0.05 was considered significant.RESULTS Out of 20 patients,the mean age was 37 years.The cohort comprised 13 males.OPAT was administered at home in 15 cases and at nursing homes in 5 cases,with nine patients receiving treatment from family members and 11 patients receiving care from a local nurse.The infections requiring OPAT included:Kidney-urinary tract(6 cases),gastrointestinal tract(4 cases),respiratory tract(4 cases),meningitis(3 cases),endocarditis(2 cases),and multiple visceral abscesses(1 case).Nineteen out of 20 patients achieved afebrile status.Half of the patients did not receive education,counselling,or demonstrations prior to discharge,but all patients rated the service as good/excellent.According to doctors’feedback,OPAT is highly beneficial and effective for patients when systematically implemented with daily telephonic monitoring,but faces challenges due to the lack of standardized protocols,dedicated teams,and adequate resources.The implementation of OPAT resulted in a reduction of hospitalization duration by an average of two weeks.CONCLUSION This pilot study proves that OPAT is safe,feasible,and efficacious by reducing two weeks of hospitalization in resource-poor settings.OPAT contributes directly to antimicrobial stewardship by reducing hospital stays and hospital-acquired complications,which is vital in combating antimicrobial resistance(AMR)and aligns with the global action plan for AMR in infection prevention and optimal antimicrobial utilization.
文摘Aim Dental biofilms are complex communities composed largely of harmless bacteria. Certain pathogenic species including Streptococcus mutans （S. mutans） can become predominant when host factors such as dietary sucrose intake imbalance the biofilm ecology. Current approaches to control S. mutans infection are not pathogen-specific and eliminate the entire oral community along with any protective benefits provided. Here, we tested the hypothesis that removal of S. mutans from the oral community through targeted antimicrobial therapy achieves protection against subsequent S. mutans colonization. Methodology Controlled amounts of S. mutans were mixed with S. mutans-free saliva, grown into biofilms and visualized by antibody staining and cfu quantization. Two specifically-targeted antimicrobial peptides （STAMPs） against S. mutans were tested for their ability to reduce S. mutans biofilm incorporation upon treatment of the inocula. The resulting biofilms were also evaluated for their ability to resist subsequent exogenous S. mutans colonization. Results S. mutans colonization was considerably reduced （9 ± 0.4 fold reduction, P=0.01） when the surface was preoccupied with saliva-derived biofilms. Furthermore, treatment with S. mutans-specific STAMPs yielded S. mutans-deficient biofilms with significant protection against further S. mutans colonization （5 minutes treatment： 38 ± 13 fold reduction P=0.01; 16 hours treatment： 96 ± 28 fold reduction P=0.07）. Conclusion S. mutans infection is reduced by the pre- sence of existing biofilms. Thus maintaining a healthy or ＂normal＂ biofilm through targeted antimicrobial therapy （such as the STAMPs） could represent an effective strategy for the treatment and prevention of S. mutans colonization in the oral cavity and caries progression.
基金supported by the Construction Plan of the Tianjin Characteristic Subject Group,Oral Medical Engineering
文摘The main objective of this study is to evaluate the antibacterial effect of antibacterial pho-todynamic therapy(aPDT)on Streptococcus mutans(S.mutans)biofilm model in vitro.The selection of photosensitizers is the key step for the efficacy of photodynamic therapy(PDT).However,no studies have been conducted in the oral field to compare the functional char-acteristics and application effects of PDT mediated by various photosensitizers.In this re-search,the antibacterial effect of Methylene blue(MB)/650 nm laser and Hematoporphyrin monomethyl ether(HMME)/532 nm laser on S.mutans biofilm was compared under different energy densities to provide experimental reference for the clinical application of the two PDT.The yield of lactic acid was analyzed by Colony forming unit(CFU)and spectrophotometry,and the complete biofilm activity was measured by Confocal Laser Scanning Microscopy(CLSM)to evaluate the bactericidal effect on each group.Based on the results of CFU,the bacterial colonies formed by 30.4J/cm^(2)532nm MB-aPDT group and 30.4J/cm^(2)532nm HMME-aPDT group were significantly less than those in other groups,and the bacterial colonies in HMME-aPDT group were less than those in HMME-aPDT group.Lactic acid production in all treatment groups except the photosensitizer group was statistically lower than that in the normal saline control group.The activity of bacterial plaque biofilm was significantly decreased in the two groups treated with 30.4 J/cm^(2) aPDT.Therefore,aPDT suitable for energy measurement can kill S.mutans plaque biofilm,and MB-aPDT is better than HMME-aPDT.
基金support for this work from DoD Army STTR Award No.W911NF-22-P-0018the Florida High Tech Corridor Council(FHTCC)matching grant,and the Air Force Office of Scientific Research FA9550-20-1-0063 and FA9550-23-1-0656.
文摘Antibiotic administration is the mainstay for treating bacterial infections,but multidrug-resistant(MDR)bacteria jeopardize its effectiveness.Antimicrobial photodynamic therapy(aPDT)offers a promising strategy with less risk of inducing resistance,yet the lack of a suitable wearable light source limits its widespread adoption.Here,we design flexible quantum dot light-emitting diodes(F-QLEDs)for effective aPDT treatment of MDR bacteria.By simultaneous optical,thermal,and reliability management,we achieved F-QLEDs with emission spectrum matching the photosensitizer absorption,physiologically safe surface temperature(<41℃),enhanced operating lifetime(7.5X),and ambient shelf life>1 month.Subsequently,aPDT testing demonstrated a~9-log reduction of Staphylococcus aureus and~2-3 log reduction of Pseudomonas aeruginosa compared to controls.Additionally,testing with different photosensitizers confirmed F-QLED versatility for targeted aPDT.These results showcase the potent antimicrobial efficacy of F-QLEDs and their potential as wearable optical platforms for point-of-care treatment of MDR infections and broader photomedical applications.
基金the National Natural Science Foundation of China(U1803109)the National Key Research and Development Program of China(2018YFC1602500)+6 种基金the National Natural Science Foundation of China(81572032)Major scientific and technological innovation projects in Shandong Province(2019JZZY010719)National Key Research and Development Program(2019YFA0904003)Six Talent Peaks Project in Jiangsu Province(2016-WSN-112)Key research and development project of Jiangsu provincial science and Technology Department(BE2017654)Gusu key health talent of Suzhou,Jiangsu youth medical talents program(QN-867)the Science and Technology Program of Suzhou(SZS201715)。
文摘Klebsiella pneumoniae is one of the major pathogens causing global multidrug-resistant infections.Therefore,strategies for preventing and controlling the infections are urgently needed.Phage depolymerase,often found in the tail fiber protein or the tail spike protein,is reported to have antibiofilm activity.In this study,phage P560isolated from sewage showed specific for capsule locus type KL47 K.pneumoniae,and the enlarged haloes around plaques indicated that P560 encoded a depolymerase.The capsule depolymerase,ORF43,named P560dep,derived from phage P560 was expressed,purified,characterized and evaluated for enzymatic activity as well as specificity.We reported that the capsule depolymerase P560dep,can digest the capsule polysaccharides on the surface of KL47 type K.pneumoniae,and the depolymerization spectrum of P560dep matched to the host range of phage P560,KL47 K.pneumoniae.Crystal violet staining assay showed that P560dep was able to significantly inhibit biofilm formation.Further,a single dose(50μg/mouse)of depolymerase intraperitoneal injection protected 90%–100%of mice from lethal challenge before or after infection by KL47 carbapenem-resistant K.pneumoniae.And pathological changes were alleviated in lung and liver of mice infected by KL47 type K.pneumoniae.It is demonstrated that depolymerase P560dep as an attractive antivirulence agent represents a promising tool for antimicrobial therapy.
基金supported by C3 Jian Inc, Delta Dental-California and UCLA Oppenheimer Award
文摘Dental caries （tooth decay） is caused by a specific group of cariogenic bacteria, like Streptococcus mutans, which convert dietary sugars into acids that dissolve the mineraI in tooth structure. Killing cariogenic bacteria is an effective way to control or prevent tooth decay. In a previous study, we discovered a novel compound （Glycyrrhizol A）, from the extraction of licorice roots, with strong antimicrobial activity against cariogenic bacteria. In the current study, we developed a method to produce these specific herbal extracts in large quantities, and then used these extracts to develop a sugar-free lollipop that effectively kills cariogenic bacteria like Streptococcus mutans. Further studies showed that these sugar-free lollipops are safe and their antimicrobial activity is stable. Two pilot human studies indicate that a brief application of these lollipops （twice a day for ten days） led to a marked reduction of cariogenic bacteria in oral cavity among most human subjects tested. This herbal lollipop could be a novel tool to promote oral health through functional foods.
文摘The most common cause of admission to the Pediatric Dentistry service is dental pain, active deafness and an oppressive sensation that is sometimes<span> throbbing and burning. Pharmacotherapy in Pediatric Dentistry must be effective, safe, and rational in neonates, infants, and children. The pharmacotherapeutic follow-up of pediatric patients from Integral Clinic of the Odontopediatric Specialty</span><span> </span><span>(CLIO) and Kindergarten Clinic (CLIJANI), Autonom</span><span>ous University of Zacatecas</span><span> </span><span>(UAZ) was carried out. Through an observa</span><span>tion</span><span>al, exploratory, and cross-sectional study, 23 patients from the Pediatric Dentistry Specialty Clinic (CLIO/UAO/UAZ) and 35 clinical records of patients </span><span>from CLIJANI, from August 2019-2020, were analyzed.</span><span> </span><span>Prior authorization</span><span> for </span><span>the patient, an interview, and pharmacotherapeutic follow-up were per</span><span>formed, recording data on the indicated drug, the dose, and the schedule of use.</span><span> </span><span>On carrying out the interview on pharmacotherapy with the parents or guardians who accompany the patient, 91.3% of the pediatric patients were not administered pharmacological treatment. It was observed that there is no adequate adherence to the pharmacological treatment in pediatric patients</span><span>.</span>
文摘Sepsis,defined as life-threatening organ dysfunction caused by a dysregulated host response to infection,remains a major challenge in critical care and a leading cause of mortality worldwide.Early,appropriate antibiotic administration is among the most effective strategies to improve outcomes,making optimization of antimicrobial therapy a priority.Optimal antibiotic therapy is the careful selection of the agent and dosing regimen that optimizes outcomes while minimizing adverse effects and antimicrobial resistance.Yet,paradoxically,dosing regimens in sepsis often rely on standardized protocols that overlook fundamental biological variables such as sex and gender,as well as intersecting factors like socioeconomic status,ethnicity,and access to care.[1]This omission compromises efficacy and perpetuates clinical inequalities.
基金supported by a grant from the NSFC/RGC Joint Research Scheme sponsored by the Research Grants Council of the Hong Kong Special Administrative Region,China and the National Natural Science Foundation of China(Project No.N_HKU706/20 and No.82061160492)Human third molars were obtained from patients who provided written informed consent,and the study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster(IRB No:UW22-657)+1 种基金Human saliva was collected from a volunteer who provided written informed consent,which was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster(IRB No:UW22-657)All animal-related operations in this work were approved by the Ethics Committee of Anhui Medical University,China(ref.no.LLSC20232002).
文摘The single-function agents with wide-spectrum activity which tend to disturb the ecological balance of oral cavity cannot satisfy dental treatment need.A multi-functional agent with specifically targeted killing property and in situ remineralization is warranted for caries management.A novel multi-functional agent(8DSS-C8-P-113)consisting of three domains,i.e.,a non-specific antimicrobial peptide(AMP)(P-113),a competence stim-ulating peptide(C8),and an enhancing remineralization domain(8DSS),is fabricated and evaluated in this study.The findings demonstrates that 2μM mL^(-1)of 8DSS-C8-P-113 eliminates planktonic Streptococcus mutans(S.mutans)without disrupting the oral normal flora.At a concentration of 8μM mL^(-1),it exhibits the ability to prevent S.mutans’adhesion.Furthermore,8DSS-C8-P-113 self-assembles a hydrogel state at the higher con-centration of 16μM mL^(-1).This hydrogel self-adheres on the tooth surface,resisting acid attack,eradicating S.mutans’biofilm,and inducing mineralization in order to facilitate the repair of demineralized dental hard tissue.Its significant effectiveness in reducing the severity of dental caries is also demonstrated in vivo in a rat model.This study suggests that the multi-functional bioactive AMP 8DSS-C8-P-113 is a promising agent to specifically target pathogen,prevent tooth demineralization,and effectively induce in situ bio-mimic reminer-alization for the management of dental caries.
基金granted by the National Key Technologies R&D Program(Nos.2023YFB3809904,and 2023YFE0119200)the National Natural Science Foundation of China(No.52301185)+1 种基金the Key Project of Changsha Health Commission(No.KJ-A2023013)Sichuan Provincial Natural Science Foundation(No.2023NSFSC0633).
文摘Periodontitis is a prevalent chronic inflammatory disease driven by biofilms formed by common oral pathogens,leading to the progressive destruction of periodontal tissues.However,conventional antimicrobial therapies often neglect the clearance of bacterial endotoxins such as lipopolysaccharide(LPS),a potent pro-inflammatory mediator that exacerbates tissue inflammation.To address this problem,we developed a multifunctional nanoreactor featuring both antibacterial and LPS-scavenging capabilities.Utilizing a photochemical synthesis strategy,Ag-TiO_(2) nanoparticles with diameters below 10 nm were grown in situ onto micro-scale carriers 13X zeolite and activated carbon(AC).The 13X matrix enhances photocatalytic oxidative activity,while AC offers a high specific surface area for the adsorption of LPS and hydrogen sulfide(H2S).The Ag-TiO_(2) photocatalyst further endows the system with self-cleaning ability and improved degradation efficiency of harmful agents.Under 405 nm blue light emitting diode(LED)light irradiation,the composite efficiently generates reactive oxygen species(ROS),achieving>98% bactericidal rates against Actinobacillus Actinomycetemcomitans(A.actinomycetemcomitans),Streptococcus mutans(S.mutans),and Porphyromonas gingivalis(P.gingivalis),with up to 80% biofilm removal.Additionally,AC-Ag-TiO_(2) effectively adsorbs and degrades LPS,significantly reducing the secretion of inflammatory cytokines such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in macrophages.In a mouse model of periodontitis,the material not only stabilized the oral microbiota but also promoted periodontal tissue repair.Taken together,this study introduces a multi-scale catalytic platform that synergistically combines photocatalysis and adsorption to achieve dual antibacterial and anti-inflammatory effects,offering a highly efficient and long-lasting therapeutic strategy for periodontitis.
基金the National Natural Science Foundation of China(22271197)the Guangdong Basic and Applied Basic Research Foundation(2023A1515011578)+2 种基金the Shenzhen Science and Technology Program(RCYX20221008092924059,JCYJ20220531102601003)Shenzhen Key Laboratory of Functional Aggregate Materials(ZDSYS20211021111400001)the 2035 Research Excellence Program of Shenzhen University(2023C001).
文摘Cationic compounds with quaternary ammonium structures are one of the most commonly utilized antibacterial materials,which can effectively overcome the emergence of bacterial drug resistance.Systematic investigation on the structure-activity relationship of such cationic compounds is essential for the development of efficient antimicrobials toward different bacterial strains with clear antimicrobial mechanisms.In this study,we rationally designed and synthesized two quaternary ammonium photosensitizers with aggregation-induced emission(AIE)properties.One possesses a unilaterally charged and Janus-type structure with two positively charged moieties at one tail and two hydrophobic alkyl chains on the other side.The other is a bilaterally symmetric molecule bearing quaternary ammonium structures at both ends.The fluorescence staining experiments,bactericidal assays,and bacterial morphology analyses reveal that the Janus-type AIE luminogen show superior photodynamic antimicrobial activities possibly due to its better disruption of the bacterial membranes.Further theoretical study on the molecule-membrane interaction and molecular dynamics gains deeper insights into the intrinsic relationships between molecular structures and antibacterial activities,which provides a feasible design strategy for high-performance antimicrobial agents.
基金financially supported by the“Summit Plan”High-Level Hospital Construction Project of Foshan(No.FSSYKF-2020002)the Medical Scientific Research Projects of Foshan Health Bureau(No.20210358)+3 种基金the National Natural Science Foundation of China(NSFC,Nos.22277153,22007104)Guangdong Basic and Applied Basic Research Foundation(No.2021B1515020050)Science,Technology and Innovation Commission of Shenzhen Municipality Project(No.JCYJ20190807152616996)the Fundamental Research Funds for the Central Universities(No.22lgqb37).
文摘Bacterial infection is currently a serious challenge globally, causing death of thousands of human beings. New antimicrobial agents with novel mechanism of action are urgently needed. Transition metal complexes have shown great potentials in photodynamic and photocatalytic therapy. Herein, we take full advantage of metal photocatalyst and successfully developed a novel cyclometalated iridium(Ⅲ) complex(Ir1) with higher biofilm damage efficiency than the clinical antibiotics. Ir1 synergistically generates reactive oxygen species and coenzyme photocatalytic activity with high efficiency under white light irradiation. Combined with these properties, Ir1 exhibited excellent photoinactivation of S. aureus and effectively damaged the biofilm. This work provides a new approach for the development of antibacterial photodynamic therapy.
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.
基金supported by the National Natural Science Foundation of China(82170950,82272150)National Health Commission of the People’s Republic of China(WKJ-ZJ-2214)Wenzhou Basic Scientific Research Project(Grant No.Y20240323).
文摘Dental caries is primarily caused by cariogenic bacteria metabolizing carbohydrates to produce acidic substances that erode the dental hard tissues.Traditional remineralization treatments often have limited efficacy due to their lack of antibacterial activity.According to the Interrupting Dental Caries(IDC)theory,ideal caries-preventive materials should possess both antibacterial and remineralizing properties.Furthermore,effective adhesion to dental surfaces is crucial.Inspired by the wet adhesion properties of the salivary acquired pellicle,we developed a multifunctional gargle named Ce6@PDN-SAP(CP-SAP).This formulation employed peptide dendrimer nanogels(PDN)as a carrier for the photosensitizer Ce6,further functionalized with saliva-acquired peptide(SAP)to confer wet adhesion properties.CP-SAP rapidly adhered to the dental surface and remained effective for extended periods.Upon laser irradiation,Ce6 generated reactive oxygen species(ROS),disrupting bacterial outer membrane integrity,causing protein leakage,and reducing ATP levels,thereby achieving potent antibacterial effects.Following this,PDN and SAP acted as nucleation templates to promote in situ remineralization of demineralized dental hard tissues.In vivo studies using rat models demonstrated that CP-SAP provided significantly superior caries-preventive effects compared to chlorhexidine gargle.In conclusion,CP-SAP,as an innovative approach grounded in the IDC theory,holds great promise for the prevention and treatment of dental caries.
基金financial supported by the National Natural Science Foundation of China(81771084(M.-Q.D.),51703187(Z.X.))supported by The Chongqing Talents of Exceptional Young Talents Project(CQYC202005029).
文摘Early childhood caries(ECC)is a public healthcare concern that greatly reduces the quality of life of young children.As a leading factor of ECC,cariogenic biofilms are composed of acidogenic/aciduric pathogens and extracellular polysaccharides(EPSs),creating an acidic and protected microenvironment.Antimicrobial photodynamic therapy(aPDT)is a noninvasive,painless,and efficient therapeutic approach that is suitable for treating ECC.However,due to the hyperfine structure of cariogenic biofilms,most photosensitizers(PSs)could not access and penetrate deeply in biofilms,which dramatically hamper their efficiency in the clinic.Herein,bioresponsive nanoparticle loaded with chlorin e6(MPP-Ce6)is developed,which largely increases the penetration depth(by over 75%)and retention(by over 100%)of PS in the biofilm compared with free Ce6.Furthermore,MPP-Ce6-mediated aPDT not only kills the bacteria in preformed biofilms but also inhibits multispecies biofilm formation.A rampant caries model is established to mimic ECC in vivo,where the population of cariogenic bacteria is decreased to 10%after MPP-Ce6-mediated aPDT.Importantly,the number and severity of carious lesions are efficiently reduced via Keyes’scoring and micro-CT analysis.This simple but effective strategy can serve as a promising approach for daily oral hygiene in preventing ECC.
基金This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
文摘Sepsis is defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection.[1]Sepsis was responsible for approximately 20%of deaths worldwide before the corona virus disease pandemic and has been characterized as a global health priority by the World Health Organization.[2]Therapy for sepsis is characterized by rapid initiation of antimicrobial therapy,fluid resuscitation,and non-specific supportive care.[3]Antimicrobial therapy is subsequently tailored if an inciting organism is identified or specific organisms are confidently ruled out.International guidelines,such as the Surviving Sepsis Campaign,have been associated with improved outcomes by putting together a compendium of evidence-based recommendations based on GRADE methodology.
基金supported by the National Key R&D Program of China(2023YFF1103900)National Natural Science Foundation of China(31902304,31972167)the Open Project Program of State Key Laboratory of Food Nutrition and Safety,Tianjin University of Science&Technology(SKLFNS-KF-202310).
文摘Considering the increasing abundance of antibiotic-resistant bacteria,novel antimicrobial approaches need to be investigated.Photothermal therapy(PTT),an innovative noninvasive therapeutic technique,has demonstrated significant potential in addressing drug-resistant bacteria and bacterial biofilms.However,when used in isolation,PTT requires higher-temperature conditions to effectively eradicate bacteria,thereby potentially harming healthy tissues and inducing new inflammation.This study aims to present a comprehensive review of nanomaterials with intrinsic antimicrobial properties,antimicrobial materials relying on photothermal action,and nanomaterials using drug delivery antimicrobial action,along with their applications in antimicrobials.Additionally,the synergistic mechanisms of these antimicrobial approaches are elucidated.The review provides a reference for developing multifunctional photothermal nanoplatforms for treating bacterially infected wounds.
基金Dr.Rolf M.Schwiete Foundationthe Federal Ministry of Education and Research,Germany(BMBFFKZ:13GW0439B)for the financial support of this work.
文摘Polydimethylsiloxane(PDMS)is widely used in biomedical applications due to its biocompatibility,chemical stability,flexibility,and resistance to degradation in physiological environments.However,its intrinsic inertness limits further(bio)functionalization,and its hydrophobic recovery compromises the longevity of conventional surface modifications.To address these challenges,we developed a nanoprecipitation method for the straight-forward colloidal deposition,covalent thermal crosslinking,and surface anchoring of a chemically tunable,biocompatible polyacrylamide with reactive hydroxyl groups,enabling further surface modifications.This polymer incorporates~6%bioinspired catechol units,introduced via an elegant one-pot Kabachnik-Fields re-action,to facilitate thermally induced network formation and enhance adhesion to plasma-activated PDMS.The resulting uniform coatings exhibited tunable dry layer thicknesses up to 44±7 nm and effectively suppressed PDMS chain rearrangement even after steam autoclaving,ensuring long-term stability in aqueous and ambient environments for at least 90 days.The bioactive post-modification potential was demonstrated in a proof-of-concept study by immobilizing the photosensitizer rose bengal at surface concentrations of 20 or 40μg cm^(-2).The coating exhibited antimicrobial activity against S.aureus,achieving a 4-log reduction(99.99%)in colony-forming units after 30 min of irra-diation at 554 nm(342 J cm^(-2)),even when bacteria were suspended in liquid,without direct surface contact.In contrast,antimicrobial activity against E.coli was only observed with minimized liquid volume,bringing the motile bacteria into close contact with the surface.This work established a straightforward and versatile strategy for the stable and bioactive functionalization of PDMS surfaces for application in non-invasive surface decontamination.
基金supported by the National Natural Science Foundation of China(82172211,92268206)the National Key Research and Development Programs of China(2022YFA1104300)+5 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research Projects(2022-JCJQ-ZB-09600,2023-JSKY-SSQG-006)the Natural Science Foundation of Sichuan Province(2023NSFSC0339)the 1·3·5 Project for Disciplines of Excellence of West China Hospital,Sichuan University(ZYGD22008)the China Postdoctoral Science Foundation(2022TQ0223,2022M722256)the Post-Doctor Research Project of West China Hospital,Sichuan University(2023HXBH031).
文摘Electrospun nanofibrous membranes(eNFMs)have been extensively developed for bio-applications due to their structural and compositional similarity to the natural extracellular matrix.However,the emergence of antibiotic resistance in bacterial infections significantly impedes the further development and applications of eNFMs.The development of antibacterial nanomaterials substantially nourishes the engineering design of antibacterial eNFMs for combating bacterial infections without relying on antibiotics.Herein,a comprehensive review of diverse fabrication techniques for incorporating antibacterial nanomaterials into eNFMs is presented,encompassing an exhaustive introduction to various nanomaterials and their bactericidal mechanisms.Furthermore,the latest achievements and breakthroughs in the application of these antibacterial eNFMs in tissue regenerative therapy,mainly focusing on skin,bone,periodontal and tendon tissues regeneration and repair,are systematically summarized and discussed.In particular,for the treatment of skin infection wounds,we highlight the antibiotic-free antibacterial therapy strategies of antibacterial eNFMs,including(i)single model therapies such as metal ion therapy,chemodynamic therapy,photothermal therapy,and photodynamic therapy;and(ii)multimodel therapies involving arbitrary combinations of these single models.Additionally,the limitations,challenges and future opportunities of antibacterial eNFMs in biomedical applications are also discussed.We anticipate that this comprehensive review will provide novel insights for the design and utilization of antibacterial eNFMs in future research.
