RESUMO
Photothermal therapy (PTT) and magnetic hyperthermia therapy (MHT) using 2D nanomaterials (2DnMat) have recently emerged as promising alternative treatments for cancer and bacterial infections, both important global health challenges. The present review intends to provide not only a comprehensive overview, but also an integrative approach of the state-of-the-art knowledge on 2DnMat for PTT and MHT of cancer and infections. High surface area, high extinction coefficient in near-infra-red (NIR) region, responsiveness to external stimuli like magnetic fields, and the endless possibilities of surface functionalization, make 2DnMat ideal platforms for PTT and MHT. Most of these materials are biocompatible with mammalian cells, presenting some cytotoxicity against bacteria. However, each material must be comprehensively characterized physiochemically and biologically, since small variations can have significant biological impact. Highly efficient and selective in vitro and in vivo PTTs for the treatment of cancer and infections are reported, using a wide range of 2DnMat concentrations and incubation times. MHT is described to be more effective against bacterial infections than against cancer therapy. Despite the promising results attained, some challenges remain, such as improving 2DnMat conjugation with drugs, understanding their in vivo biodegradation, and refining the evaluation criteria to measure PTT or MHT effects.
Assuntos
Infecções Bacterianas , Hipertermia Induzida , Nanoestruturas , Neoplasias , Animais , Humanos , Hipertermia Induzida/métodos , Fototerapia/métodos , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Infecções Bacterianas/terapia , Fenômenos Magnéticos , MamíferosRESUMO
Multidrug-resistant (MDR) bacteria constitute one of the most serious global health threats. The increasing incidence rate of bacterial infections caused by MDR strains and the decrease in the number of newly developed antibiotics have prompted the scientific community to search for alternatives. One such alternative is the use of bacteriophages. In this review, we discuss the most critical MDR organisms, including Acinetobacter baumanni, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus The efficacy of phage therapy against MDR bacteria is also discussed. We included studies from the last 10 years that examined the efficacy of phage therapy against MDR pathogens. In addition, this review highlights the effect of bacteriophages against bacterial biofilms. The existing knowledge indicates that phage therapy is a potential therapeutic strategy against MDR bacteria. However, the adverse effects of phage therapy, such as toxicity, and the emergence of phage resistance have not yet been resolved.
Assuntos
Infecções Bacterianas , Bacteriófagos , Staphylococcus aureus Resistente à Meticilina , Humanos , Farmacorresistência Bacteriana Múltipla , Infecções Bacterianas/terapia , Infecções Bacterianas/microbiologia , Bactérias , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: The emergence of ciprofloxacin-resistant bacteria is a serious challenge worldwide, bringing the need to find new approaches to manage this bacterium. Bacteriophages (phages) have been shown inhibitory effects against ciprofloxacin-resistance bacteria; thus, ciprofloxacin resistance or tolerance may not affect the phage's infection ability. Additionally, researchers used phage-ciprofloxacin combination therapy for the inhibition of multidrug-resistant bacteria. RESULTS: The sublethal concentrations of ciprofloxacin could lead to an increase in progeny production. Antibiotic treatments could enhance the release of progeny phages by shortening the lytic cycle and latent period. Thus, sublethal concentrations of antibiotics combined with phages can be used for the management of bacterial infections with high antibiotic resistance. In addition, combination therapy exerts various selection pressures that can mutually decrease phage and antibiotic resistance. Moreover, phage ciprofloxacin could significantly reduce bacterial counts in the biofilm community. Immediate usage of phages after the attachment of bacteria to the surface of the flow cells, before the development of micro-colonies, could lead to the best effect of phage therapy against bacterial biofilm. Noteworthy, phage should be used before antibiotics usage because this condition may have allowed phage replication to occur first before ciprofloxacin interrupted the bacterial DNA replication process, thereby interfering with the activity of the phages. Furthermore, the phage-ciprofloxacin combination showed a promising result for the management of Pseudomonas aeruginosa infections in mouse models. Nevertheless, low data are existing about the interaction between phages and ciprofloxacin in combination therapies, especially regarding the emergence of phage-resistant mutants. Additionally, there is a challenging and important question of how the combined ciprofloxacin with phages can increase antibacterial functions. Therefore, more examinations are required to support the clinical usage of phage-ciprofloxacin combination therapy.
Assuntos
Infecções Bacterianas , Bacteriófagos , Infecções por Pseudomonas , Animais , Camundongos , Ciprofloxacina/farmacologia , Ciprofloxacina/uso terapêutico , Bacteriófagos/fisiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/terapia , Infecções por Pseudomonas/microbiologiaRESUMO
The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.
Assuntos
Infecções Bacterianas , Grafite , Nanocompostos , Neoplasias , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/terapia , Linhagem Celular Tumoral , Grafite/uso terapêutico , Humanos , Imagem Multimodal , Nanocompostos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fototerapia , Nanomedicina Teranóstica/métodosRESUMO
Photothermal therapy (PTT) has attracted extensive attention in disease treatments. However, conventional photothermal systems do not possess a temperature-control mechanism, which poses a serious risk to healthy tissues and/or organs due to inevitable thermal damage. Herein, a smart photothermal nanosystem with an intrinsic temperature-control mechanism for thermostatic treatment of bacterial infections is reported. The smart photothermal nanosystem is constructed by loading a thermochromic material into a hollow-structured silica nanocarrier, in which the thermochromic material is composed of naturally occurring phase-change materials (PCMs), a proton-responsive spirolactone, and a proton source. The resulting nanosystem shows strong near-infrared (NIR) absorption and efficient photothermal conversion in solid PCMs but becomes NIR-transparent when PCMs are melted upon NIR irradiation. Such an attractive feature can precisely regulate the photothermal equilibrium temperature to the melting point of PCMs, regardless of the variation in external experimental parameters. In contrast to conventional PTT with severe thermal damage, the reported smart photothermal nanosystem provides an internal protection mechanism on healthy tissues and/or organs, which remarkably accelerates the recovery of bacteria-infected wounds. The smart photothermal nanosystem is a versatile PTT platform, holding great promise in the safe and efficient treatment of bacterial infections and multimodality synergistic therapy.
Assuntos
Infecções Bacterianas , Nanopartículas , Neoplasias , Humanos , Temperatura , Prótons , Neoplasias/terapia , Dióxido de Silício , Fototerapia/métodos , Infecções Bacterianas/terapiaRESUMO
Background: Essential health and nutrition services for pregnant women, newborns, and children, particularly in low- and middle-income countries (LMICs), are disrupted by the COVID-19 pandemic. This formative research was conducted at five LMICs to understand the pandemic's impact on barriers to and mitigation for strategies of care-seeking and managing possible serious bacterial infection (PSBI) in young infants. Methods: We used a convergent parallel mixed-method design to explore the possible factors influencing PSBI management, barriers, and facilitators at three levels: 1) national and local policy, 2) the health systems, public and private facilities, and 3) community and caregivers. We ascertained trends in service provision and utilisation across pre-lockdown, lockdown, and post-lockdown periods by examining facility records and community health worker registers. Results: The pandemic aggravated pre-existing challenges in the identification of young infants with PSBI; care-seeking, referral, and treatment due to several factors at the policy level (limited staff and resource reallocation), health facility level (staff quarantine, sub-optimal treatment in facilities, limited duration of service availability, lack of clear guidelines on the management of sick young infants, and inadequate supplies of protective kits and essential medicines) and at the community level (travel restrictions, lack of transportation, and fear of contracting the infection in hospitals). Care-seeking shifted to faith healers, traditional and informal private sources, or home remedies. However, caregivers were willing to admit their sick young infants to the hospital if advised by doctors. A review of facility records showed low attendance (<50%) of sick young infants in the OPD/emergencies during lockdowns in Bangladesh, India (both sites) and Pakistan, but it gradually increased as lockdowns eased. Stakeholders suggested aspirational and pragmatic mitigation strategies. Conclusions: We obtained useful insights on health system preparedness during catastrophes and strategies to strengthen services and improve utilisation regarding PSBI management. The current pandemic provides an opportunity for implementing various mitigation strategies at the policy, health system, and community levels to improve preparedness.
Assuntos
Infecções Bacterianas , COVID-19 , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/terapia , COVID-19/epidemiologia , Criança , Controle de Doenças Transmissíveis , Feminino , Humanos , Lactente , Recém-Nascido , Pandemias , Gravidez , Encaminhamento e ConsultaRESUMO
Bacterial infection is the leading cause of many serious inflammation diseases threatening human health. Existing theranostic options for bacterial infection are always complicated and unsatisfactory. There is an increasing interest in developing a more effective theranostic approach for the treatment of infections. Herein, we report the development of a near-infrared (NIR) chemiluminescent (CL) nanoparticles ALPBs containing luminol, AIE dye (TTDC), PCPDTBT, and nitric oxide (NO) donor (BNN6), which could achieve a deep CL imaging-guided photothermal-NO gas therapy of bacterial infection. After intravenous injection, ALPBs could be largely accumulated in the infected site and then activated by oversecreted reactive oxygen species (ROS) to produce near-infrared chemiluminescence, which could precisely track infection-induced local inflammation. Under the guidance of imaging, synergistic photothermal-NO therapy was further performed by 808 nm laser irradiation, leading to active bacterial eradication and rapid recovery of infected tissues. The utility of ALPBs provides a powerful and controllable "all-in-one" platform for combating bacterial infection.
Assuntos
Infecções Bacterianas , Nanopartículas , Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/terapia , Humanos , Inflamação , Óxido Nítrico , Doadores de Óxido Nítrico , Fototerapia , Terapia Fototérmica , Nanomedicina Teranóstica/métodosRESUMO
The development of antibiotics resistance has made multidrug-resistant (MDR) bacterial infection one of the most serious global health issues. Photothermal therapy (PTT) is an emerging therapeutic mode which can be applied to bacterial infection without inducing resistance. Moreover, enhanced therapeutic efficacy and less tissue damage can be realized with NIR-II fluorescence imaging (FLI) guided PTT. Herein, a polymeric luminogen with aggregation-induced emission (AIEgens) characteristics, poly(dithieno[3,2-b:2',3'-d]pyrrole-benzo[1,2-c:4,5-c']bis([1,2,5]thiadiazole)) (PDTPTBT), was synthesized and used as a photothermal agent for PTT of bacterial infections. PDTPTBT was encapsulated into liposomes (L-PDTPTBT) for improved water dispersibility. Upon 808 nm NIR irradiation, L-PDTPTBT can eliminate multiple bacteria including the Gram-positive methicillin-resistant Staphylococcus aureus and Enterococcus faecalis, the Gram-negative Escherichia coli and Pseudomonas aeruginosa. Serious damage of bacterial membrane and leakage of cytoplasm is observed after photothermal treatment using L-PDTPTBT. The potential of the formulation has been demonstrated in two infected animal models: (i) a subcutaneous abscess model and (ii) a diabetic skin infection model. In the diabetic skin infection model, the death of mice is largely suppressed and the wounds can heal more quickly with treatment of L-PDTPTBT under NIR irradiation. The excellent photothermal bactericidal ability and low cytotoxicity make L-PDTPTBT potential candidate for treating MDR bacterial infections in the future.
Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Infecções Bacterianas/terapia , Camundongos , Fototerapia/métodos , PolímerosRESUMO
Multidrug-resistant (MDR) pathogenic bacterial infections have become a major danger to public health. Synergetic therapy through multiple approaches is more powerful than the respective one alone, but has been rarely achieved in defeating MDR bacterial infections so far. Herein, indocyanine green-functionalized Mn3 O4 nanosheets are engineered as an efficient and safe antibacterial agent with photothermal, photodynamic, and oxidase-like activities, which display powerful ability in treating MDR bacterial infections. Therein, photothermal and photodynamic activities can be triggered by a single low-powered near-infrared laser (808 nm, 0.33 W cm-2 ), resulting in the generation of localized hyperthermia (photothermal conversion efficiency, 67.5%) and singlet oxygen. Meanwhile, oxidase-like activity of this material further leads to the generation of hydroxyl radical as well as superoxide radical. Sheet-like structure with rough surfaces make them tends to adhere on bacterial surface and thus damage membrane system as well as influence bacterial metabolism. As a result, Gram-positive and Gram-negative bacteria can both be eradicated. Animal experiments further indicate that the functionalized Mn3 O4 nanosheets can effectively treat methicillin-resistant Staphylococcus aureus-infected wounds through the triple synergetic therapy. Moreover, toxicity evaluation in vitro and in vivo has proved the superior biosafety of this material, which is promising to apply in clinical anti-infective therapy.
Assuntos
Infecções Bacterianas , Farmacorresistência Bacteriana Múltipla , Hipertermia Induzida , Raios Infravermelhos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Infecções Bacterianas/terapia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hipertermia Induzida/métodos , Staphylococcus aureus Resistente à Meticilina , Nanoestruturas , Oxirredutases/farmacologiaRESUMO
The alarming rise in antimicrobial resistance coupled with a lack of innovation in antibiotics has renewed interest in the development of alternative therapies to combat bacterial infections. Despite phage therapy demonstrating success in various individual cases, a comprehensive and unequivocal demonstration of the therapeutic potential of phages remains to be shown. The co-evolution of phages and their bacterial hosts resulted in several inherent limitations for the use of natural phages as therapeutics such as restricted host range, moderate antibacterial efficacy, and frequent emergence of phage-resistance. However, these constraints can be overcome by leveraging recent advances in synthetic biology and genetic engineering to provide phages with additional therapeutic capabilities, improved safety profiles, and adaptable host ranges. Here, we examine different ways phages can be engineered to deliver heterologous therapeutic payloads to enhance their antibacterial efficacy and discuss their versatile applicability to combat bacterial pathogens.
Assuntos
Infecções Bacterianas , Bacteriófagos , Terapia por Fagos , Antibacterianos/farmacologia , Bactérias/genética , Infecções Bacterianas/terapia , Bacteriófagos/genética , HumanosRESUMO
Bovine colostrum (BC), the first milk produced from cows after parturition, is increasingly used as a nutritional supplement to promote gut function and health in other species, including humans. The high levels of whey and casein proteins, immunoglobulins (Igs), and other milk bioactives in BC are adapted to meet the needs of newborn calves. However, BC supplementation may improve health outcomes across other species, especially when immune and gut functions are immature in early life. We provide a review of BC composition and its effects in infants and children in health and selected diseases (diarrhea, infection, growth-failure, preterm birth, necrotizing enterocolitis (NEC), short-bowel syndrome, and mucositis). Human trials and animal studies (mainly in piglets) are reviewed to assess the scientific evidence of whether BC is a safe and effective antimicrobial and immunomodulatory nutritional supplement that reduces clinical complications related to preterm birth, infections, and gut disorders. Studies in infants and animals suggest that BC should be supplemented at an optimal age, time, and level to be both safe and effective. Exclusive BC feeding is not recommended for infants because of nutritional imbalances relative to human milk. On the other hand, adverse effects, including allergies and intolerance, appear unlikely when BC is provided as a supplement within normal nutrition guidelines for infants and children. Larger clinical trials in infant populations are needed to provide more evidence of health benefits when patients are supplemented with BC in addition to human milk or formula. Igs and other bioactive factors in BC may work in synergy, making it critical to preserve bioactivity with gentle processing and pasteurization methods. BC has the potential to become a safe and effective nutritional supplement for several pediatric subpopulations.
Assuntos
Fenômenos Fisiológicos da Nutrição Infantil , Colostro , Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição do Lactente , Animais , Infecções Bacterianas/terapia , Bovinos , Criança , Colostro/química , Colostro/imunologia , Doenças Fetais/terapia , Glicolipídeos/análise , Glicoproteínas/análise , Transtornos do Crescimento/terapia , Humanos , Imunoglobulinas/análise , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Enteropatias/terapia , Gotículas Lipídicas , Proteínas do Leite/análise , Oligossacarídeos/análiseRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Inhalations with thermal waters are an old therapeutic method used in the therapy of respiratory diseases as a treatment of choice showing a long-lasting outcome with no side effects. Paradoxically, there is little well-established research on their mechanisms of action. AIM OF THE STUDY: The aim of this paper is therefore to summarize the influence of inhalatory treatment with thermal waters on the main symptoms and features of respiratory disorders including allergy-like symptoms, inflammation, oxidant-anti-oxidant balance, cellular influx, disturbed mucus secretions, recurrent infections, pulmonary and nasal function and quality of life. A short history of inhalations is also presented. MATERIALS AND METHODS: The present paper is a sum-up of research articles on the use of inhalations with thermal waters in respiratory disorders. RESULTS: According to the herein presented literature, the use of thermal water inhalations is beneficial for almost all manifestations of respiratory diseases. The mode of their action remains still unclear; however, it seems that the most important one relies on the restoration of proper defense mechanisms of the organism. CONCLUSIONS: Inhalations with thermal waters alleviate symptoms of respiratory diseases. They also improve the quality of life of the patients and seem to be a good add-on therapy in the treatment of disorders of the respiratory system.
Assuntos
Balneologia , Terapia Respiratória , Doenças Respiratórias/terapia , Administração por Inalação , Animais , Infecções Bacterianas/terapia , Balneologia/história , História do Século XIX , História Antiga , História Medieval , Fontes Termais , Humanos , Inflamação/terapia , Transtornos Leucocíticos/terapia , Muco/metabolismo , Mucosa Respiratória/metabolismo , Terapia Respiratória/história , Viroses/terapia , Água/administração & dosagemRESUMO
About 100 years ago, the first antibiotic drug was introduced into health care. Since then, antibiotics have made an outstanding impact on human medicine. However, our society increasingly suffers from collateral damage exerted by these highly effective drugs. The rise of resistant pathogen strains, combined with a reduction of microbiota diversity upon antibiotic treatment, has become a significant obstacle in the fight against invasive infections worldwide.Alternative and complementary strategies to classical "Fleming antibiotics" comprise microbiota-based treatments such as fecal microbiota transfer and administration of probiotics, live-biotherapeutics, prebiotics, and postbiotics. Other promising interventions, whose efficacy may also be influenced by the human microbiota, are phages and vaccines. They will facilitate antimicrobial stewardship, to date the only globally applied antibiotic resistance mitigation strategy.In this review, we present the available evidence on these nontraditional interventions, highlight their interaction with the human microbiota, and discuss their clinical applicability.
Assuntos
Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/terapia , Farmacorresistência Bacteriana Múltipla , Microbioma Gastrointestinal , Imunidade , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/virologia , Bacteriófagos , Terapia Biológica , Disbiose , Transplante de Microbiota Fecal , Interações entre Hospedeiro e Microrganismos , Humanos , Prebióticos , Probióticos , VacinasRESUMO
Most abdominal infections are mixed infections caused by aerobic and anaerobic bacteria. Anaerobic infections are characterized by rancid secretions or abscess formation. Early implementation of source control is the key in the treatment of abdominal anaerobic infections. Damage control should be followed as one of the principles of surgical treatment. As the in vitro isolation and culture of anaerobic bacteria as well as its drug sensitivity test are time-consuming and sometimes inaccurate, the treatment of anaerobic bacteria infection is mostly empirical. Anti-infective therapy should be employed once anaerobic bacteria infection is confirmed. Ertapenem, Mosifloxacin, and Cefoperazone-sulbactam can be used for first-line monotherapy, while combination therapy can use second- or third-generation Cephalosporin, Quinolones plus Nitroimidazoles. Nutritional support and anti-shock treatment should not be neglected when implementing surgical control of infection source and antimicrobial therapy. Considering the increasing drug resistance of anaerobic bacteria, and the higher drug resistance rate in China as compared to western countries, the choice of antibiotics should be made rationally and based on epidemiological characteristics of anaerobic bacteria in different regions.
Assuntos
Antibacterianos/uso terapêutico , Bactérias Anaeróbias , Infecções Bacterianas , Infecções Intra-Abdominais/terapia , Bactérias Anaeróbias/efeitos dos fármacos , Bactérias Anaeróbias/isolamento & purificação , Infecções Bacterianas/etiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/terapia , Farmacorresistência Bacteriana , Humanos , Infecções Intra-Abdominais/etiologia , Infecções Intra-Abdominais/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Antimicrobial-resistant and novel pathogens continue to emerge, outpacing efforts to contain and treat them. Therefore, there is a crucial need for safe and effective therapies. Ultraviolet-A (UVA) phototherapy is FDA-approved for several dermatological diseases but not for internal applications. We investigated UVA effects on human cells in vitro, mouse colonic tissue in vivo, and UVA efficacy against bacteria, yeast, coxsackievirus group B and coronavirus-229E. Several pathogens and virally transfected human cells were exposed to a series of specific UVA exposure regimens. HeLa, alveolar and primary human tracheal epithelial cell viability was assessed after UVA exposure, and 8-Oxo-2'-deoxyguanosine was measured as an oxidative DNA damage marker. Furthermore, wild-type mice were exposed to intracolonic UVA as an in vivo model to assess safety of internal UVA exposure. Controlled UVA exposure yielded significant reductions in Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis, Clostridioides difficile, Streptococcus pyogenes, Staphylococcus epidermidis, Proteus mirabilis and Candida albicans. UVA-treated coxsackievirus-transfected HeLa cells exhibited significantly increased cell survival compared to controls. UVA-treated coronavirus-229E-transfected tracheal cells exhibited significant coronavirus spike protein reduction, increased mitochondrial antiviral-signaling protein and decreased coronavirus-229E-induced cell death. Specific controlled UVA exposure had no significant effect on growth or 8-Oxo-2'-deoxyguanosine levels in three types of human cells. Single or repeated in vivo intraluminal UVA exposure produced no discernible endoscopic, histologic or dysplastic changes in mice. These findings suggest that, under specific conditions, UVA reduces various pathogens including coronavirus-229E, and may provide a safe and effective treatment for infectious diseases of internal viscera. Clinical studies are warranted to further elucidate the safety and efficacy of UVA in humans.
Assuntos
Infecções Bacterianas/terapia , Micoses/terapia , Infecções Oportunistas/terapia , Terapia Ultravioleta/métodos , Viroses/terapia , Animais , Apoptose/efeitos da radiação , Bactérias/efeitos da radiação , Infecções Bacterianas/microbiologia , Sobrevivência Celular/efeitos da radiação , Colo/microbiologia , Colo/efeitos da radiação , Coronavirus Humano 229E/efeitos da radiação , Dano ao DNA/efeitos da radiação , Modelos Animais de Doenças , Enterovirus Humano B/efeitos da radiação , Feminino , Células HeLa , Humanos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos da radiação , Masculino , Camundongos , Micoses/microbiologia , Infecções Oportunistas/microbiologia , Cultura Primária de Células , Terapia Ultravioleta/efeitos adversos , Viroses/virologia , Leveduras/efeitos da radiaçãoRESUMO
In the last century, life expectancy has increased considerably, thanks to the introduction of antibiotics, hygiene and vaccines that have contributed to the cure and prevention of many infectious diseases. The era of antimicrobial therapy started in the nineteenth century with the identification of chemical compounds with antimicrobial properties. However, immediately after the introduction of these novel drugs, microorganisms started to become resistant through different strategies. Although resistance mechanisms were already present before antibiotic introduction, their large-scale use and mis-use have increased the number of resistant microorganisms. Rapid spreading of mobile elements by horizontal gene transfer such as plasmids and integrative conjugative elements (ICE) carrying multiple resistance genes has dramatically increased the worldwide prevalence of relevant multi drug-resistant human pathogens such as Staphylococcus aureus, Neisseria gonorrhoeae, and Enterobacteriaceae. Today, antimicrobial resistance (AMR) remains one of the major global concerns to be addressed and only global efforts could help in finding a solution. In terms of magnitude the economic impact of AMR is estimated to be comparable to that of climate global change in 2030. Although antibiotics continue to be essential to treat such infections, non-antibiotic therapies will play an important role in limiting the increase of antibiotic resistant microorganisms. Among non-antibiotic strategies, vaccines and therapeutic monoclonal antibodies (mAbs) play a strategic role. In this review, we will summarize the evolution and the mechanisms of antibiotic resistance, and the impact of AMR on life expectancy and economics.
Assuntos
Resistência Microbiana a Medicamentos/imunologia , Vacinas/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções Bacterianas/terapia , Biotecnologia/métodos , Biotecnologia/tendências , Farmacorresistência Bacteriana/imunologia , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Infecções/tratamento farmacológico , Infecções/imunologia , Infecções/terapia , Modelos Imunológicos , Vacinas/imunologia , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Vacinas de mRNARESUMO
Significance: In the host-microbe microenvironment, bioelectrical factors influence microbes and hosts as well as host-microbe interactions. This article discusses relevant mechanistic underpinnings of this novel paradigm. It also addresses how such knowledge may be leveraged to develop novel electroceutical solutions to manage biofilm infection. Recent Advances: Systematic review and meta-analysis of several hundred wound studies reported a 78.2% prevalence of biofilms in chronic wounds. Biofilm infection is a major cause of delayed wound healing. In the host-microbe microenvironment, bioelectrical factors influence interactions between microbes and hosts. Critical Issues: Rapid biological responses are driven by electrical signals generated by ion currents moving across cell membranes. Bacterial life, growth, and function rely on a bioelectrical milieu, which when perturbed impairs their ability to form a biofilm, a major threat to health care. Electrokinetic stability of several viral particles depend on electrostatic forces. Weak electrical field strength, otherwise safe for humans, can be anti-microbial in this context. In the host, the electric field enhanced keratinocyte migration, bolstered immune defenses, improved mitochondrial function, and demonstrated multiple other effects consistent with supporting wound healing. A deeper mechanistic understanding of bioelectrical principles will inform the design of next-generation electroceuticals. Future Directions: This is an opportune moment in time as there is a surge of interest in electroceuticals in medicine. Projected to reach $35.5 billion by 2025, electroceuticals are becoming a cynosure in the global market. The World Health Organization reports that more than 50% of surgical site infections can be antibiotic resistant. Electroceuticals offer a serious alternative.
Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/etiologia , Infecções Bacterianas/terapia , Biofilmes/efeitos dos fármacos , Terapia por Estimulação Elétrica/métodos , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/terapia , Antibacterianos/farmacologia , Biofilmes/crescimento & desenvolvimento , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Infecção da Ferida Cirúrgica/diagnósticoRESUMO
The emergence of antibiotic-resistant bacteria in the last century is alarming and calls for alternative, nonchemical treatment strategies. Thermal medicine uses heat for the treatment of infectious diseases but its use in facultative and obligate intracellular bacteria remains poorly studied. In this review, we summarize previous research on reducing the infectious burden of Mycobacterium ulcerans and Chlamydia trachomatis by using water-filtered infrared A-radiation (wIRA), a special form of heat radiation with high tissue penetration and low thermal load on the skin surface. Mycobacterium ulcerans is a thermosensitive bacterium causing chronic necrotizing skin disease. Therefore, previous data on wIRA-induced improvement of wound healing and reduction of wound infections is summarized first. Then, pathogenesis and treatment of infections with M. ulcerans causing Buruli ulcer and of those with C. trachomatis infecting the ocular conjunctiva and resulting in blinding trachoma are discussed. Both bacteria cause neglected tropical diseases and have similar geographical distributions. Results of previous in vitro and in vivo studies using wIRA on M. ulcerans and C. trachomatis infections are presented. Finally, technical aspects of using wIRA in patients are critically reviewed and open questions driving future research are highlighted. In conclusion, wIRA is a promising tool for reducing infectious burden due to intracellular bacteria such as M. ulcerans and C. trachomatis.
Assuntos
Infecções Bacterianas/terapia , Infecções por Chlamydiaceae/terapia , Hipertermia Induzida/métodos , Mycobacterium/patogenicidade , HumanosRESUMO
Chronic inflammatory diseases of the prostate are one of the most common andurological nosology. This group of diseases includes heterogeneous pathology such as chronic bacterial prostatitis, chronic non-infectious prostatitis, prostate asymptomatic inflammation and chronic pelvic pain syndrome. Currently, biological and physiotherapeutic chronic prostate inflammatory diseases treatment methods are actively being studied, such as platelet rich plasma (PRP) therapy and low-intensity pulsed ultrasound (LIPUS) therapy. Aim - assessment of the efficacy of the treatment model of chronic nonspecific bacterial prostatitis which includes combined application of transurethral vacuum drainage with PRP electrophonophoresis and transrectal LIPUS of prostate gland. A prospective clinical study was conducted on a contingent of 50 patients of "Men's Health Clinic" (Kiev, Ukraine) suffering from chronic nonspecific bacterial prostatitis (ICD-10: N41.1). LIPUS and PRP combination demonstrates the further progress of the therapeutic effect in terms of difficulty urinating (p=0,04) and a subjective decrease of life quality (p≤0,01). Overall I-PSS score indicates a decrease in the overall severity to a mild level (p≤0,01). VAS level of pelvic pain shoved the significant clinical effect of LIPUS and PRP combination (p≤0,01). LIPUS and PRP combination showed efficacy in reduction of leucocytes in ejaculate (p≤0,01), normalization of semen acidity (p≤0,01) and mucus production (p≤0,01). Treatment model of chronic nonspecific bacterial prostatitis which includes combined application of transurethral vacuum drainage with PRP electrophonophoresis and transrectal LIPUS as an addition to standard antibiotic therapy had shown deep positive impact on prostate inflammation. Effects of PRP and LIPUS combined application are additive to effects of traditional interventions in general results of therapy, life quality, pain reduction and normalization of ejaculate parameters of patients with chronic prostate inflammation.
Assuntos
Terapia por Estimulação Elétrica , Paracentese , Plasma Rico em Plaquetas , Prostatite/terapia , Ressecção Transuretral da Próstata , Terapia por Ultrassom , Ondas Ultrassônicas , Infecções Bacterianas/terapia , Doença Crônica , Humanos , Masculino , Estudos Prospectivos , UcrâniaRESUMO
New, biocompatible materials with favorable antibacterial activity are highly desirable. In this work, we develop a unique conjugated polymer featuring aggregation-induced emission (AIE) for reliable bacterial eradication. Thanks to the AIE and donor-π-acceptor structure, this polymer shows a high reactive oxygen species (ROS)-generation ability compared to a low-mass model compound and the common photosensitizer Chlorin E6. Moreover, the selective binding of pathogenic microorganisms over mammalian cells was found, demonstrating its biocompatibility. The effective growth inhibition of bacteria upon polymer treatment under light irradiation was validated inâ vitro and inâ vivo. Notably, the recovery from infection after treatment with our polymer is faster than that with cefalotin. Thus, this polymer holds great promise in fighting against bacteria-related infections in practical applications.