RESUMO
With the coming of the post-antibiotic era, there is an increasingly urgent need for safe and efficient antibacterial vaccines. Bacterial outer membrane vesicles (OMVs) have received increased attention recently as a potential subunit vaccine. OMVs are non-replicative and contain the principle immunogenic bacterial antigen, which circumvents the safety concerns of live-attenuated vaccines. Here, we developed a novel nano-vaccine by coating OMVs onto PEGylated nano-Rehmannia glutinosa polysaccharide (pRL) in a structure consisting of concentric circles, resulting in a more stable vaccine with improved immunogenicity. The immunological function of the pRL-OMV formulation was evaluated in vivo and in vitro, and the underlying mechanism was studied though transcriptomic analysis. The pRL-OMV formulation significantly increased dendritic cell (DC) proliferation and cytokine secretion. Efficient phagocytosis of the formulation by DCs was accompanied by DC maturation. Further, the formulation demonstrated superior lymph node targeting, contributing to a potent mixed cellular response and bacterial-specific antibody response against Bordetella bronchiseptica infection. Specifically, transcriptomic analysis revealed that the immune protection function correlated with T-cell receptor signalling and Th1/Th2/Th17 differentiation, among other markers of enhanced immunological activity. These findings have implications for the future application of OMV-coated nano-carriers in antimicrobial immunotherapy.
Assuntos
Membrana Externa Bacteriana , Rehmannia , Rehmannia/química , Animais , Camundongos , Membrana Externa Bacteriana/imunologia , Células Dendríticas/imunologia , Polissacarídeos/imunologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Vesículas Extracelulares/imunologia , Vacinas Bacterianas/imunologia , Feminino , Nanopartículas/químicaRESUMO
Prostate biopsies are commonly performed for the early detection of prostate cancer and yet are associated with risks of life-threatening infections. Drug-resistant strains of Escherichia coli are the most common etiologic agents. Multiple maneuvers can reduce the risk of postbiopsy infections and sepsis during transrectal prostate biopsy including periprocedural empiric or targeted prophylactic antibiotics (based on previous rectal culture) and prebiopsy rectal cleansing with a povidone-iodine solution. The transperineal approach is associated with a very low risk of infection without requiring antibiotic prophylaxis.
Assuntos
Antibioticoprofilaxia , Próstata , Neoplasias da Próstata , Reto , Humanos , Masculino , Próstata/patologia , Reto/microbiologia , Neoplasias da Próstata/patologia , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Biópsia/efeitos adversos , Cuidados Pré-Operatórios/métodos , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/etiologiaRESUMO
Aquaculture is part of the crucial industry that supplies food, especially for the global human population that is gradually increasing annually. Innovations of culture techniques have been improved throughout the years but aquaculture is regularly susceptible to bacterial and viral diseases. Numerous factors could contribute to occurrence of disease and usually they are from environmental or human stressors on the cultured animals. Synthetic chemicals in commercial treatments may yield fast results however, the side effects are usually unknown until it has taken effect. Therefore, biological control methods to treat diseases in aquaculture are preferred. This mini review provides an overview of different potential biocontrol practices for treatment of bacterial and viral diseases. Bacteriophage causes death of pathogenic bacteria by killing the cell and continue to multiply until all targeted pathogenic bacteria are eliminated. Probiotic, prebiotic, synbiotic, biofloc, and immunostimulants are beneficial products from the respective organisms that are effective in inhibiting pathogens. Vaccines introduce inactivated pathogen into the body to stimulate the immune system, while genetic modifications involve alteration and selection of disease resistant genetics.
Assuntos
Aquicultura , Infecções Bacterianas , Viroses , Aquicultura/métodos , Animais , Viroses/prevenção & controle , Viroses/imunologia , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/imunologia , Probióticos/uso terapêutico , Bacteriófagos/fisiologia , Agentes de Controle Biológico , Bactérias/genética , Humanos , PrebióticosRESUMO
Perioperative antibiotic prophylaxis (PAP) in lung transplant recipients (LuTRs) has high heterogeneity between centers. Our aim was to investigate retrospectively the approach to PAP in our center over a 20-year period (2002-2023), and its impact on early post-operative infections (EPOIs) after lung transplantation (LuT). Primary endpoint was diagnosis of EPOI, defined as any bacterial infection including donor-derived events diagnosed within 30 days from LuT. Main exposure variables were type of PAP (combination vs. monotherapy) and PAP duration. We enrolled 111 LuTRs. PAP consisted of single-agent or combination regimens in 26 (25.2%) and 85 (74.8%) LuTR. Median PAP duration was 10 days (IQR 6-13) days. Piperacillin/tazobactam was the most common agent used either as monotherapy (n = 21, 80.7%) or as combination with levofloxacin (n = 79, 92.9%). EPOIs were diagnosed in 30 (27%) patients. At multivariable analysis no advantages were found for combination regimens compared to single-agent PAP in preventing EPOI (OR: 1.57, 95% CI: 0.488-5.068, p:0.448). The impact of PAP duration on EPOIs development was investigated including duration of PAP ≤6 days as main exposure variables, without finding a significantly impact (OR:2.165, 95% CI: 0.596-7.863, p: 0.240). Our results suggest no advantages for combination regimens PAP in preventing EPOI in LuTR.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Antibioticoprofilaxia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Adulto , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Idoso , Combinação Piperacilina e Tazobactam/uso terapêutico , Combinação Piperacilina e Tazobactam/administração & dosagem , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/etiologia , Complicações Pós-Operatórias/prevenção & controle , Quimioterapia CombinadaRESUMO
SUMMARYHealthcare-associated infections (HAIs) represent a burden for public health with a high prevalence and high death rates associated with them. Pathogens with a high potential for antimicrobial resistance, such as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and Clostridioides difficile, are responsible for most HAIs. Despite the implementation of infection prevention and control intervention, globally, HAIs prevalence is stable and they are mainly due to endogenous pathogens. It is undeniable that complementary to infection prevention and control measures, prophylactic approaches by active or passive immunization are needed. Specific groups at-risk (elderly people, chronic condition as immunocompromised) and also healthcare workers are key targets. Medical procedures and specific interventions are known to be at risk of HAIs, in addition to hospital environmental exposure. Vaccines or monoclonal antibodies can be seen as attractive preventive approaches for HAIs. In this review, we present an overview of the vaccines and monoclonal antibodies in clinical development for prevention of the major bacterial HAIs pathogens. Based on the current state of knowledge, we look at the challenges and future perspectives to improve prevention by these means.
Assuntos
Anticorpos Monoclonais , Infecções Bacterianas , Vacinas Bacterianas , Infecção Hospitalar , Humanos , Infecção Hospitalar/prevenção & controle , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/imunologia , Infecções Bacterianas/epidemiologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/imunologia , Vacinas Bacterianas/imunologiaRESUMO
BACKGROUND: Twice-yearly mass distribution of azithromycin to children is a promising intervention to reduce childhood mortality in sub-Saharan Africa. The World Health Organization recommended restricting distribution to infants 1 to 11 months of age to mitigate antimicrobial resistance, although this more limited treatment had not yet been tested. METHODS: We randomly assigned rural communities in Niger to four twice-yearly distributions of azithromycin for children 1 to 59 months of age (child azithromycin group), four twice-yearly distributions of azithromycin for infants 1 to 11 months of age and placebo for children 12 to 59 months of age (infant azithromycin group), or placebo for children 1 to 59 months of age. Census workers who were not aware of the group assignments monitored mortality twice yearly over the course of 2 years. We assessed three primary community-level mortality outcomes (deaths per 1000 person-years), each examining a different age group and pairwise group comparison. RESULTS: A total of 1273 communities were randomly assigned to the child azithromycin group (1229 were included in the analysis), 773 to the infant azithromycin group (751 included in the analysis), and 954 to the placebo group (929 included in the analysis). Among 382,586 children, 419,440 person-years and 5503 deaths were recorded. Lower mortality among children 1 to 59 months of age was observed in the child azithromycin group (11.9 deaths per 1000 person-years; 95% confidence interval [CI], 11.3 to 12.6) than in the placebo group (13.9 deaths per 1000 person-years; 95% CI, 13.0 to 14.8) (representing 14% lower mortality with azithromycin; 95% CI, 7 to 22; P<0.001). Mortality among infants 1 to 11 months of age was not significantly lower in the infant azithromycin group (22.3 deaths per 1000 person-years; 95% CI, 20.0 to 24.7) than in the placebo group (23.9 deaths per 1000 person-years; 95% CI, 21.6 to 26.2) (representing 6% lower mortality with azithromycin; 95% CI, -8 to 19). Five serious adverse events were reported: three in the placebo group, one in the infant azithromycin group, and one in the child azithromycin group. CONCLUSIONS: Azithromycin distributions to children 1 to 59 months of age significantly reduced mortality and was more effective than treatment of infants 1 to 11 months of age. Antimicrobial resistance must be monitored. (Funded by the Bill and Melinda Gates Foundation; AVENIR ClinicalTrials.gov number, NCT04224987.).
Assuntos
Antibacterianos , Azitromicina , Infecções Bacterianas , Mortalidade da Criança , Mortalidade Infantil , Administração Massiva de Medicamentos , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Infecções Bacterianas/mortalidade , Infecções Bacterianas/prevenção & controle , Quimioprevenção/efeitos adversos , Quimioprevenção/estatística & dados numéricos , Farmacorresistência Bacteriana , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/estatística & dados numéricos , Níger/epidemiologia , População Rural/estatística & dados numéricosAssuntos
Antibacterianos , Azitromicina , Infecções Bacterianas , Administração Massiva de Medicamentos , Humanos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Lactente , Pré-Escolar , Níger/epidemiologia , Mortalidade Infantil , Mortalidade da Criança , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/métodos , Administração Massiva de Medicamentos/estatística & dados numéricos , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos , Quimioprevenção/estatística & dados numéricos , Farmacorresistência Bacteriana , Infecções Bacterianas/mortalidade , Infecções Bacterianas/prevenção & controleRESUMO
Healthcare associated infections (HCAI) represent a significant burden worldwide contributing to morbidity and mortality and result in substantial economic consequences equating to billions annually. Although the impacts of HCAI have been felt for many years, the coronavirus pandemic has had a profound effect, escalating rates of HCAI, even with extensive preventative measures such as vaccination, personal protective equipment, and deep cleaning regimes. Therefore, there is an urgent need for new solutions to mitigate this serious health emergency. In this paper, the fabrication of nitric oxide (NO) releasing dual action polymer coatings for use in healthcare applications is described. The coatings are doped with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and release high payloads of NO in a sustained manner for in excess of 50 hours. These coatings are extensively characterized in multiple biologically relevant solutions and the antibacterial/antiviral efficacy is studied. For the first time, we assess antibacterial activity in a time course study (1, 2, 4 and 24 h) in both nutrient rich and nutrient poor conditions. Coatings exhibit excellent activity against Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus (MRSA), with up to complete reduction observed over 24 hours. Additionally, when tested against SARS-CoV-2, the coatings significantly reduced active virus in as little as 10 minutes. These promising results suggest that these coatings could be a valuable addition to existing preventative measures in the fight against HCAIs.
Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Óxido Nítrico , Pseudomonas aeruginosa , SARS-CoV-2 , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , S-Nitroso-N-Acetilpenicilamina/química , S-Nitroso-N-Acetilpenicilamina/farmacologia , COVID-19/prevenção & controle , Antivirais/farmacologia , Antivirais/química , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/química , Animais , Infecções Bacterianas/prevenção & controleAssuntos
Farmacorresistência Bacteriana Múltipla , Transplante de Órgãos , Transplantados , Humanos , Transplante de Órgãos/efeitos adversos , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/microbiologia , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Portador Sadio/microbiologia , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
There are conflicting recommendations on whether to use or not to use fluoroquinolone prophylaxis in pediatric oncology patients. An international pediatric clinical practice guideline (CPG) recommends administering levofloxacin prophylaxis in patients with acute myeloblastic leukemia and relapsed acute lymphoblastic leukemia receiving intensive chemotherapy as this practice has been found to reduce episodes of fever and bacteremia. A separate European CPG does not recommend levofloxacin prophylaxis because of concerns for adverse effects, including potentiation of fluoroquinolone resistance and possible increased resistance to other classes of antibiotics. The nuance of the decision to give or not give prophylaxis is discussed in the context of published evidence defining the risks and benefits of levofloxacin prophylaxis for pediatric leukemia patients at high risk for bacterial infection. Knowledge gaps are also identified to guide further investigations to optimize the use of fluoroquinolone prophylaxis in pediatric patients receiving chemotherapy for cancer or undergoing a hematopoietic cell transplantation.
Assuntos
Antibacterianos , Antibioticoprofilaxia , Levofloxacino , Humanos , Criança , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Levofloxacino/uso terapêutico , Levofloxacino/administração & dosagem , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Guias de Prática Clínica como Assunto , Neoplasias/tratamento farmacológico , Bacteriemia/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/tratamento farmacológicoRESUMO
BACKGROUND: Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT. METHODS: In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data. RESULTS: Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16). CONCLUSION: In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.
Assuntos
Infecções Bacterianas , Transplante de Fígado , Complicações Pós-Operatórias , Humanos , Masculino , Transplante de Fígado/efeitos adversos , Fatores de Risco , Estudos Prospectivos , Lactente , Feminino , Pré-Escolar , Infecções Bacterianas/microbiologia , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/epidemiologia , Doença Hepática Terminal/cirurgiaRESUMO
Bacterial biofilms commonly cause chronic and persistent infections in humans. Bacterial biofilms consist of an inner layer of bacteria and an autocrine extracellular polymeric substance (EPS). Biofilm dispersants (abbreviated as dispersants) have proven effective in removing the bacterial physical protection barrier EPS. Dispersants are generally weak or have no bactericidal effect. Bacteria dispersed from within biofilms (abbreviated as dispersed bacteria) may be more invasive, adhesive, and motile than planktonic bacteria, characteristics that increase the probability that dispersed bacteria will recolonize and cause reinfection. The dispersants should be combined with antimicrobials to avoid the risk of severe reinfection. Dispersant-based nanoparticles have the advantage of specific release and intense penetration, providing the prerequisite for further antibacterial agent efficacy and achieving the eradication of biofilms. Dispersant-based nanoparticles delivered antimicrobial agents for the treatment of diseases associated with bacterial biofilm infections are expected to be an effective measure to prevent reinfection caused by dispersed bacteria. KEY POINTS: ⢠Dispersed bacteria harm and the dispersant's dispersion mechanisms are discussed. ⢠The advantages of dispersant-based nanoparticles in bacteria biofilms are discussed. ⢠Dispersant-based nanoparticles for cutting off reinfection in vivo are highlighted.
Assuntos
Antibacterianos , Biofilmes , Nanopartículas , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Nanopartículas/química , Antibacterianos/farmacologia , Humanos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Reinfecção/prevenção & controle , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Matriz Extracelular de Substâncias Poliméricas/química , Matriz Extracelular de Substâncias Poliméricas/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the role of levofloxacin combined with recombinant human granulocyte colony-stimulating factor (G-CSF) or only G-CSF supportive therapy in preventing infection in autologous hematopoietic stem cell transplantation(ASCT), and to analyze the length of hospital stay, hospitalization cost and post-transplant survival of the patients. METHODS: A retrospective analysis was performed in the patients with hematological malignancies who accepted ASCT at our hospital from January 2012 to July 2022, the febrile neutropenia, the incidence of bacterial infection and the use rate of intravenous antibiotics in the levofloxacin+G-CSF group and only G-CSF support group during ASCT were observed. The length of hospital stay, total cost during hospitalization and survival after 90 days of transplantation between the two groups were compared. RESULTS: A total of 102 cases were included in this study, including 57 cases of multiple myeloma, 36 cases of acute leukaemia, 7 cases of lymphoma, 3 cases of myelodysplastic syndrome, 1 case of light chain amyloidosis, and 1 case of POEMS syndrome. 47 patients received levofloxacin+ G-CSF antibacterial prophylaxis, and 55 patients received G-CSF supportive therapy. In the levofloxacin+ G-CSF group, 40 cases (85.11%) developed febrile neutropenia, and 13 cases (27.66%) were confirmed as bacterial infection. In the G-CSF group, 44 cases (80.00%) developed febrile neutropenia, and 16 cases (29.09%) were bacterial infection. There was no statistically significant difference in the incidence of febrile neutropenia and bacterial infection between the two groups (χ2=0.46ï¼P =0.50; χ2=0.03ï¼P =0.87). The use rate of intravenous antibiotics in the levofloxacin+ G-CSF group was 85.11% (40/47), which was not statistically different from 85.45% (47/55) in the G-CSF group (χ2=0.04ï¼P =0.84). The detection rates of levofloxacin-resistant bacteria in the levofloxacin+ G-CSF group and G-CSF group were 8.57% (3/35) and 21.43% (6/28), respectively, with no statistical difference (χ2=0.65, P >0.05). The median length and median cost of hospitalization in the levofloxacin+ G-CSF group and G-CSF group were 25 d vs 22 d and 78 216.24 yuan vs 80 724.38 yuan, with no statistically significant differences ( t =3.00ï¼P =0.09; t =0.94ï¼P =0.09). Within 90 days after transplantation, two cases (4.26%) died in the levofloxacin+ G-CSF group and one case (1.82%) died in the G-CSF group, with no statistically significant difference between the two groups (χ2=0.53ï¼P =0.47). CONCLUSION: Application of levofloxacin+ G-CSF showed no significant benefit compared to G-CSF support for the prevention of bacterial infections during ASCT.
Assuntos
Fator Estimulador de Colônias de Granulócitos , Transplante de Células-Tronco Hematopoéticas , Levofloxacino , Transplante Autólogo , Humanos , Estudos Retrospectivos , Infecções Bacterianas/prevenção & controle , Antibacterianos , MasculinoRESUMO
Vaccination has become a widely used method to induce immune protection against microbial pathogens, including viral and bacterial microorganisms. Both humoral and cellular immunity serve a critical role in neutralizing and eliminating these pathogens. An effective vaccine should be able to induce a long-lasting immune memory response. Recent investigations on different subsets of T cells have identified a new subset of T cells using multi-parameter flow cytometry, which possess stem cell-like properties and the ability to mount a rapid immune response upon re-exposure to antigens known as stem cell-like memory T cells (TSCM). One of the major challenges with current vaccines is their limited ability to maintain long-term memory in the adaptive immune system. Recent evidence suggests that a specific subgroup of memory T cells has the unique ability to retain their longevity for up to 25 years, as observed in the case of the yellow fever vaccine. Therefore, in this study, we tried to explore and discuss the potential role of this new T cell memory subset in the development of viral and bacterial vaccines.
Assuntos
Vacinas Bacterianas , Memória Imunológica , Células T de Memória , Vacinas Virais , Humanos , Animais , Vacinas Virais/imunologia , Vacinas Bacterianas/imunologia , Células T de Memória/imunologia , Viroses/imunologia , Viroses/prevenção & controle , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , VacinaçãoRESUMO
Regarding several infectious diseases in fish, multiple vaccinations are not favorable. The chimeric multiepitope vaccine (CMEV) harboring several antigens for multi-disease prevention would enhance vaccine efficiency in terms of multiple disease prevention. Herein, the immunogens of tilapia's seven pathogens including E. tarda, F. columnare, F. noatunensis, S. iniae, S. agalactiae, A. hydrophila, and TiLV were used for CMEV design. After shuffling and annotating the B-cell epitopes, 5,040 CMEV primary protein structures were obtained. Secondary and tertiary protein structures were predicted by AlphaFold2 creating 25,200 CMEV. Proper amino acid alignment in the secondary structures was achieved by the Ramachandran plot. In silico determination of physiochemical and other properties including allergenicity, antigenicity, glycosylation, and conformational B-cell epitopes were determined. The selected CMEV (OSLM0467, OSLM2629, and OSLM4294) showed a predicted molecular weight (MW) of 70 kDa, with feasible sites of N- and O-glycosylation, and a number of potentially conformational B-cell epitope residues. Molecular docking, codon optimization, and in-silico cloning were tested to evaluate the possibility of protein expression. Those CMEVs will further elucidate in vitro and in vivo to evaluate the efficacy and specific immune response. This research will highlight the new era of vaccines designed based on in silico structural vaccine design.
Assuntos
Epitopos de Linfócito B , Doenças dos Peixes , Simulação de Acoplamento Molecular , Tilápia , Animais , Tilápia/imunologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Epitopos de Linfócito B/imunologia , Viroses/prevenção & controle , Viroses/imunologia , Vacinas Bacterianas/imunologia , Vacinas Virais/imunologia , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/imunologia , Epitopos/imunologiaRESUMO
Bacteriophage (phage) has been reported to reduce the bacterial infection in delayed-healing wounds and, as a result, aiding in the healing of said wounds. In this study we investigated whether the presence of phage itself could help repair delayed-healing wounds in diabetic mice. Three strains of phage that target Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa were used. To prevent the phage liquid from running off the wound, the mixture of phage (phage-cocktail) was encapsulated in a porous hydrogel dressing made with three-dimensional printing. The phage-cocktail dressing was tested for its phage preservation and release efficacy, bacterial reduction, cytotoxicity with 3T3 fibroblast, and performance in repairing a sterile full-thickness skin wound in diabetic mice. The phage-cocktail dressing released 1.7%-5.7% of the phages embedded in 24 h, and reduced between 37%-79% of the surface bacteria compared with the blank dressing (p <.05). The phage-cocktail dressing exhibited no sign of cytotoxicity after 3 days (p <.05). In vivo studies showed that 14 days after incision, the full-thickness wound treated with a phage-cocktail dressing had a higher wound healing ratio compared with the blank dressing and control (p <.01). Histological analysis showed that the structure of the skin layers in the group treated with phage-cocktail dressing was restored in an orderly fashion. Compared with the blank dressing and control, the repaired tissue in the phage-cocktail dressing group had new capillary vessels and no sign of inflammation in its dermis, and its epidermis had a higher degree of re-epithelialization (p <.05). The slow-released phage has demonstrated positive effects in repairing diabetic skin wounds.
Assuntos
Infecções Bacterianas , Bacteriófagos , Hidrogéis , Cicatrização , Animais , Camundongos , Infecções Bacterianas/terapia , Infecções Bacterianas/prevenção & controle , Hidrogéis/química , Bandagens , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , MasculinoRESUMO
The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.
Assuntos
Antibacterianos , Nanoestruturas , Propriedades de Superfície , Antibacterianos/farmacologia , Antibacterianos/química , Nanoestruturas/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Humanos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controleRESUMO
Repeated exposure to antibiotics and changes in the diet and environment shift the gut microbial diversity and composition, making the host susceptible to pathogenic infection. The emergence and ongoing spread of AMR pathogens is a challenging public health issue. Recent evidence showed that probiotics and prebiotics may play a role in decolonizing drug-resistant pathogens by enhancing the colonization resistance in the gut. This review aims to analyze available evidence from human-controlled trials to determine the effect size of probiotic interventions in decolonizing AMR pathogenic bacteria from the gut. We further studied the effects of prebiotics in human and animal studies. PubMed, Embase, Web of Science, Scopus, and CINAHL were used to collect articles. The random-effects model meta-analysis was used to pool the data. GRADE Pro and Cochrane collaboration tools were used to assess the bias and quality of evidence. Out of 1395 citations, 29 RCTs were eligible, involving 2871 subjects who underwent either probiotics or placebo treatment to decolonize AMR pathogens. The persistence of pathogenic bacteria after treatment was 22%(probiotics) and 30.8%(placebo). The pooled odds ratio was 0.59(95% CI:0.43-0.81), favoring probiotics with moderate certainty (p = 0.0001) and low heterogeneity (I2 = 49.2%, p = 0.0001). The funnel plot showed no asymmetry in the study distribution (Kendall'sTau = -1.06, p = 0.445). In subgroup, C. difficile showed the highest decolonization (82.4%) in probiotics group. Lactobacillus-based probiotics and Saccharomyces boulardii decolonize 71% and 77% of pathogens effectively. The types of probiotics (p < 0.018) and pathogens (p < 0.02) significantly moderate the outcome of decolonization, whereas the dosages and regions of the studies were insignificant (p < 0.05). Prebiotics reduced the pathogens from 30% to 80% of initial challenges. Moderate certainty of evidence suggests that probiotics and prebiotics may decolonize pathogens through modulation of gut diversity. However, more clinical outcomes are required on particular strains to confirm the decolonization of the pathogens. Protocol registration: PROSPERO (ID = CRD42021276045).
Assuntos
Bactérias , Microbioma Gastrointestinal , Prebióticos , Probióticos , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Probióticos/farmacologia , Humanos , Prebióticos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Bactérias/classificação , Bactérias/isolamento & purificação , Animais , Resultado do Tratamento , Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/prevenção & controle , Trato Gastrointestinal/microbiologiaRESUMO
Children with congenital or acquired asplenia or hyposplenism have an increased risk for severe and even life-threatening infections mainly due to encapsulated bacteria. Current practice focuses on preventing severe infections with timely administration of vaccinations, antibacterial prophylaxis when indicated, and urgent evaluation and treatment of febrile events. As new vaccines are now available for both children and adults with asplenia/hyposplenism, we present an up-to-date recommendation on the prevention and management of acute infections in children with asplenia/hyposplenism.
Assuntos
Guias de Prática Clínica como Assunto , Humanos , Criança , Esplenectomia , Baço/anormalidades , Infecções/etiologia , Infecções/complicações , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Infecções Bacterianas/prevenção & controleRESUMO
Blood-contact medical devices are indispensable for clinical interventions, yet their susceptibility to thrombosis and bacterial infections poses substantial risks to treatment efficacy and patient well-being. This study introduces a polysulfobetaine/alginate-CuII (SAC) zwitterionic hydrogel coating on polyurethane (PU) surfaces. This approach retains the superhydrophilic and antifouling nature of pSBMA while conferring the antibacterial effects of copper ions. Meanwhile, the copper alginate network intertwines with the polysulfobetaine (pSBMA) network, enhancing its mechanical properties and overcoming inherent weaknesses, thereby improving coating durability. Compared to the substrate, the SAC hydrogel coating significantly reduces thrombus adhesion mass by approximately 81.5% during extracorporeal blood circulation and effectively prevents bacterial biofilm formation even in a high-concentration bacterial milieu over 30 days. Moreover, the results from an isolated blood circulation model in New Zealand white rabbits affirm the impressive anticoagulant efficacy of the SAC hydrogel coating. The findings suggest that this hydrogel coating and its application method hold promise as a solution for blood-contact material surface modification to address thrombosis and bacterial biofilm formation simultaneously.