RESUMEN
BACKGROUND: Understanding the aetiological organisms causing maternal infections is crucial to inform antibiotic treatment guidelines, but such data are scarce from Sub-Saharan Africa (SSA). We performed this systematic review and meta-analysis to address this gap. METHODS: Microbiologically confirmed maternal infection data were collected from PubMed, Embase, and African Journals online databases. The search strategy combined terms related to bacterial infection, pregnancy, postnatal period, observational studies, SSA. Exclusion criteria included colonization, asymptomatic infection, and screening studies. Pooled proportions for bacterial isolates and antimicrobial resistance (AMR) were calculated. Quality and completeness of reporting were assessed using the Newcastle-Ottawa and STROBE checklists. FINDINGS: We included 14 papers comprising data from 2,575 women from four sources (blood, urine, surgical wound and endocervical). Mixed-growth was commonly reported at 17% (95% CI: 12%-23%), E. coli from 11%(CI:10%-12%), S. aureus from 5%(CI: 5%-6%), Klebsiella spp. at 5%(CI: 4%- 5%) and Streptococcus spp. at 2%(CI: 1%-2%). We observed intra-sample and inter-sample heterogeneity between 88-92% in all meta-analyses. AMR rates were between 19% -77%, the highest with first-line beta-lactam antibiotics. Convenience sampling, and limited reporting of laboratory techniques were areas of concern. INTERPRETATION: We provide a comprehensive summary of microbial aetiology of maternal infections in SSA and demonstrate the paucity of data available for this region. We flag the need to review the current local and international empirical treatment guidelines for maternal bacterial infections in SSA because there is high prevalence of AMR among common causative bacteria. FUNDING: This research was supported by the NIHR-Professorship/NIHR300808 and the Wellcome-Strategic-award /206545/Z/17/Z. TRIAL REGISTRATION: Prospero ID CRD42021238515.
Asunto(s)
Antibacterianos , Infecciones Bacterianas , Farmacorresistencia Bacteriana , Complicaciones Infecciosas del Embarazo , Humanos , África del Sur del Sahara/epidemiología , Femenino , Embarazo , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Complicaciones Infecciosas del Embarazo/microbiología , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificaciónRESUMEN
Virulence factor genes (VFGs) play pivotal roles in bacterial infections and have been identified within the human gut microbiota. However, their involvement in chronic diseases remains poorly understood. Here, we establish an expanded VFG database (VFDB 2.0) consisting of 62,332 nonredundant orthologues and alleles of VFGs using species-specific average nucleotide identity ( https://github.com/Wanting-Dong/MetaVF_toolkit/tree/main/databases ). We further develop the MetaVF toolkit, facilitating the precise identification of pathobiont-carried VFGs at the species level. A thorough characterization of VFGs for 5452 commensal isolates from healthy individuals reveals that only 11 of 301 species harbour these factors. Further analyses of VFGs within the gut microbiomes of nine chronic diseases reveal both common and disease-specific VFG features. Notably, in type 2 diabetes patients, long HiFi sequencing confirms that shared VF features are carried by pathobiont strains of Escherichia coli and Klebsiella pneumoniae. These findings underscore the critical importance of identifying and understanding VFGs in microbiome-associated diseases.
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Microbioma Gastrointestinal , Factores de Virulencia , Humanos , Factores de Virulencia/genética , Enfermedad Crónica , Microbioma Gastrointestinal/genética , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Klebsiella pneumoniae/aislamiento & purificación , Diabetes Mellitus Tipo 2/microbiología , Diabetes Mellitus Tipo 2/genética , Escherichia coli/genética , Escherichia coli/patogenicidad , Escherichia coli/aislamiento & purificación , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/patogenicidad , Bases de Datos Genéticas , Infecciones Bacterianas/microbiologíaRESUMEN
Prokaryotic adaptive immune systems called CRISPR-Cas systems have transformed genome editing by allowing for precise genetic alterations through targeted DNA cleavage. This system comprises CRISPR-associated genes and repeat-spacer arrays, which generate RNA molecules that guide the cleavage of invading genetic material. CRISPR-Cas is classified into Class 1 (multi-subunit effectors) and Class 2 (single multi-domain effectors). Its applications span combating antimicrobial resistance (AMR), targeting antibiotic resistance genes (ARGs), resensitizing bacteria to antibiotics, and preventing horizontal gene transfer (HGT). CRISPR-Cas3, for example, effectively degrades plasmids carrying resistance genes, providing a precise method to disarm bacteria. In the context of ESKAPE pathogens, CRISPR technology can resensitize bacteria to antibiotics by targeting specific resistance genes. Furthermore, in tuberculosis (TB) research, CRISPR-based tools enhance diagnostic accuracy and facilitate precise genetic modifications for studying Mycobacterium tuberculosis. CRISPR-based diagnostics, leveraging Cas endonucleases' collateral cleavage activity, offer highly sensitive pathogen detection. These advancements underscore CRISPR's transformative potential in addressing AMR and enhancing infectious disease management.
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Infecciones Bacterianas , Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Humanos , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/genética , Edición Génica , Bacterias/genéticaRESUMEN
Periodontitis is a common chronic inflammatory disease, affecting approximately 19% of the global adult population. A relationship between periodontal disease and Alzheimer disease has long been recognized, and recent evidence has been uncovered to link these 2 diseases mechanistically. Periodontitis is caused by dysbiosis in the subgingival plaque microbiome, with a pronounced shift in the oral microbiota from one consisting primarily of Gram-positive aerobic bacteria to one predominated by Gram-negative anaerobes, such as Porphyromonas gingivalis. A common phenomenon shared by all bacteria is the release of membrane vesicles to facilitate biomolecule delivery across long distances. In particular, the vesicles released by P gingivalis and other oral pathogens have been found to transport bacterial components across the blood-brain barrier, initiating the physiologic changes involved in Alzheimer disease. In this review, we summarize recent data that support the relationship between vesicles secreted by periodontal pathogens to Alzheimer disease pathology.
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Enfermedad de Alzheimer , Periodontitis , Porphyromonas gingivalis , Enfermedad de Alzheimer/microbiología , Enfermedad de Alzheimer/metabolismo , Humanos , Periodontitis/microbiología , Porphyromonas gingivalis/patogenicidad , Disbiosis/microbiología , Infecciones Bacterianas/microbiología , Barrera Hematoencefálica/microbiología , Animales , MicrobiotaRESUMEN
BACKGROUND: Continuous monitoring of antimicrobial resistance (AMR) in Uganda involves testing bacterial isolates from clinical samples at national and regional hospitals. Although the National Microbiology Reference Laboratory (NMRL) analyzes these isolates for official AMR surveillance data, there's limited integration into public health planning. To enhance the utilization of NMRL data to better inform drug selection and public health strategies in combating antibiotic resistance, we evaluated the trends and spatial distribution of AMR to common antibiotics used in Uganda. METHODS: We analyzed data from pathogenic bacterial isolates from blood, cerebrospinal, peritoneal, and pleural fluid from AMR surveillance data for 2018-2021. We calculated the proportions of isolates that were resistant to common antimicrobial classes. We used the chi-square test for trends to evaluate changes in AMR resistance over the study period. RESULTS: Out of 537 isolates with 15 pathogenic bacteria, 478 (89%) were from blood, 34 (6.3%) were from pleural fluid, 21 (4%) were from cerebrospinal fluid, and 4 (0.7%) were from peritoneal fluid. The most common pathogen was Staphylococcus aureus (20.1%), followed by Salmonella species (18.8%). The overall change in resistance over the four years was 63-84% for sulfonamides, fluoroquinolones macrolides (46-76%), phenicols (48-71%), penicillins (42-97%), ß-lactamase inhibitors (20-92%), aminoglycosides (17-53%), cephalosporins (8.3-90%), carbapenems (5.3-26%), and glycopeptides (0-20%). There was a fluctuation in resistance of Staphylococcus aureus to methicillin (60%-45%) (using cefoxitin resistance as a surrogate for oxacillin resistance) Among gram-negative organisms, there were increases in resistance to tetracycline (29-78% p < 0.001), ciprofloxacin (17-43%, p = 0.004), ceftriaxone (8-72%, p = 0.003), imipenem (6-26%, p = 0.004), and meropenem (7-18%, p = 0.03). CONCLUSION: The study highlights a concerning increase in antibiotic resistance rates over four years, with significant increase in resistance observed across different classes of antibiotics for both gram-positive and gram-negative organisms. This increased antibiotic resistance, particularly to commonly used antibiotics like ceftriaxone and ciprofloxacin, makes adhering to the WHO's Access, Watch, and Reserve (AWaRe) category even more critical. It also emphasizes how important it is to guard against the growing threat of antibiotic resistance by appropriately using medicines, especially those that are marked for "Watch" or "Reserve."
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Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Uganda/epidemiología , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificaciónRESUMEN
BACKGROUND: Managing infectious complications after kidney transplantation (KT) remains a major challenge. Infections are the leading non-cardiovascular cause of death among kidney transplant recipients (KTr). The urinary tract is particularly vulnerable to infections in this group, leading to high levels of morbidity and mortality, as well as significant economic costs. CASE PRESENTATION: This case report presents the first documented instance of extensive thigh pyomyositis resulting from cystic fistulae in an 84-year-old KTr. The patient was referred to our hospital with acute onset fever, pain in the inner thighs and pyuria. A CT scan revealed bilateral pyomyositis of the thighs, characterized by multiple abscesses in the adductor muscles and hydroaerobic levels. Additionally, cystic fistulae complicated by pubic symphysis osteitis were identified. CONCLUSION: In KTr, lower limb pyomyositis resulting from a urinary tract infection is an extremely rare and significantly worsens the overall prognosis for these patients.
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Trasplante de Riñón , Piomiositis , Muslo , Humanos , Piomiositis/microbiología , Trasplante de Riñón/efectos adversos , Muslo/patología , Masculino , Anciano de 80 o más Años , Bacterias Anaerobias/aislamiento & purificación , Infecciones Urinarias/microbiología , Infecciones Urinarias/complicaciones , Receptores de Trasplantes , Tomografía Computarizada por Rayos X , Infecciones Bacterianas/microbiología , Fístula/etiologíaRESUMEN
Respiratory tract infections (RTIs) have a significant impact on global health, especially among children and the elderly. The key bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and non-fermenting Gram Negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa are most commonly associated with RTIs. These bacterial pathogens have evolved a diverse array of resistance mechanisms through horizontal gene transfer, often mediated by mobile genetic elements and environmental acquisition. Treatment failures are primarily due to antimicrobial resistance and inadequate bacterial engagement, which necessitates the development of alternative treatment strategies. To overcome this, our review mainly focuses on different virulence mechanisms and their resulting pathogenicity, highlighting different therapeutic interventions to combat resistance. To prevent the antimicrobial resistance crisis, we also focused on leveraging the application of artificial intelligence and machine learning to manage RTIs. Integrative approaches combining mechanistic insights are crucial for addressing the global challenge of antimicrobial resistance in respiratory infections.
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Antibacterianos , Infecciones del Sistema Respiratorio , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/clasificación , Farmacorresistencia Bacteriana , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , VirulenciaRESUMEN
While phages hold promise as an antibiotic alternative, they encounter significant challenges in combating bacterial infections, primarily due to the emergence of phage-resistant bacteria. Bacterial defence mechanisms like superinfection exclusion, CRISPR, and restriction-modification systems can hinder phage effectiveness. Innovative strategies, such as combining different phages into cocktails, have been explored to address these challenges. This review delves into these defence mechanisms and their impact at each stage of the infection cycle, their challenges, and the strategies phages have developed to counteract them. Additionally, we examine the role of phage cocktails in the evolving landscape of antibacterial treatments and discuss recent studies that highlight the effectiveness of diverse phage cocktails in targeting essential bacterial receptors and combating resistant strains.
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Bacterias , Infecciones Bacterianas , Bacteriófagos , Terapia de Fagos , Bacteriófagos/fisiología , Bacteriófagos/genética , Bacterias/virología , Bacterias/genética , Infecciones Bacterianas/terapia , Infecciones Bacterianas/microbiología , Humanos , Antibacterianos/farmacología , Farmacorresistencia BacterianaRESUMEN
Background: Antibiotic resistance (ABR) is a global challenge, and its control depends on robust evidence primarily derived from surveillance systems. Methods: We utilised a national surveillance data set to demonstrate how such evidence can be systematically generated. In doing so, we characterised the ABR profiles of priority clinical pathogens, identified associated factors, and drew inferences on antibiotic usage in Uganda. Results: Of the 12 262 samples collected between 2019-21, we analysed 9033 with complete metadata. ABR was steadily increasing at a rate of 0.5% per year, with a surge in 2021 and the highest and lowest levels of penicillin and carbapenems detected in the northern (odds ratio (OR) = 2.26; P < 0.001) and the northeast (OR = 0.28; P < 0.001) regions of Uganda respectively. ABR was commonly observed with Escherichia coli (OR = 1.18; P < 0.001) and Klebsiella pneumoniae (OR = 1.25; P < 0.001) among older and male patients (61-70 years old) (OR = 1.88; P = 0.005). Multi-drug resistance (MDR) and ABR were disproportionately higher among bloodstream infections than respiratory tract infections and urinary tract infections, often caused by Acinetobacter baumannii. Co-occurrence of ABR suggests that cephalosporins such as ceftriaxone are in high use all over Uganda. Conclusions: ABR is indeed a silent pandemic, and our results suggest it is increasing at 0.5% per year, with a notable surge in 2021 likely due to coronavirus disease 2019 (COVID-19). Of concern, ABR and MDR are mainly associated with bloodstream and surgical wound infections, with a gender and age dimension. However, it is encouraging that carbapenem resistance remains relatively low. Such evidence is critical for contextualising the implementation and evaluation of national action plans.
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Antibacterianos , Humanos , Uganda/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Preescolar , Anciano , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Niño , Lactante , Adolescente , Adulto Joven , Recién Nacido , COVID-19/epidemiología , Farmacorresistencia Bacteriana , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana MúltipleRESUMEN
The COVID-19 pandemic has altered respiratory infection patterns in pediatric populations. The emergence of the SARS-CoV-2 Omicron variant and relaxation of public health measures have increased the likelihood of coinfections. Previous studies show conflicting results regarding the impact of viral and bacterial coinfections with SARS-CoV-2 on severity of pediatric disease. This study investigated the prevalence and clinical impact of coinfections among children hospitalized with COVID-19 during the Omicron wave. A retrospective analysis was conducted on 574 hospitalized patients aged under 18 years in Russia, from January 2022 to March 2023. Samples from patients were tested for SARS-CoV-2 and other respiratory pathogens using qRT-PCR, bacterial culture tests and mass spectrometry, and ELISA. Approximately one-third of COVID-19 cases had coinfections, with viral and bacterial coinfections occurring at similar rates. Adenovirus and Staphylococcus aureus were the most common viral and bacterial coinfections, respectively. Viral coinfections were associated with higher fevers and increased bronchitis, while bacterial coinfections correlated with longer duration of illness and higher pneumonia rates. Non-SARS-CoV-2 respiratory viruses were linked to more severe lower respiratory tract complications than SARS-CoV-2 monoinfection. These findings suggest that during the Omicron wave, seasonal respiratory viruses may have posed a greater threat to children's health than SARS-CoV-2.
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Infecciones Bacterianas , COVID-19 , Coinfección , Hospitalización , SARS-CoV-2 , Humanos , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/virología , COVID-19/epidemiología , COVID-19/complicaciones , COVID-19/microbiología , Adolescente , Niño , Preescolar , Femenino , Masculino , Lactante , Federación de Rusia/epidemiología , Estudios Retrospectivos , Prevalencia , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/virología , Recién NacidoRESUMEN
Antimicrobials are the most frequently prescribed drug in pediatrics, with an estimated 37% of infants and 61% of hospitalized children having received them. Approximately 20-50% of prescriptions have been shown to be potentially unnecessary or inappropriate. The World Health Organization (WHO) estimates that the continued increase in antimicrobial resistance by the year 2050 will lead to the death of 10 million people per year. This paper describes a protocol to be used in a future study to evaluate the implementation of a quarterly syndromic antibiogram, aimed to improve the use of antibiotics for the treatment of pediatric bacterial infections at the Maputo Central Hospital, Mozambique. This study uses implementation science methods framed by the Dynamic Adaption Process (DAP) and RE-AIM conceptual frameworks to develop a multi-phase, mixed-methods evaluation utilizing qualitative and quantitative approaches. The pediatric inpatient services at HCM consist of approximately 18 physicians and 60 nurses. Additionally, the microbiology laboratory consists of eight laboratory technicians. We anticipate analyzing approximately 9,000 medical records. Qualitative methods include in-depth interviews with clinicians, laboratory technicians, and administrators to explore current knowledge and practices around antibiotic decision making, facilitators and barriers to intervention implementation, as well as acceptability and satisfaction with the intervention roll-out. Qualitative analysis will be performed with NVivo 12 software. Quantitative methods include extracting data from existing records from the pediatric ward of Hospital Central de Maputo (HCM) guided by the RE-AIM framework to explore intervention utilization and other factors influencing its implementation. Quantitative descriptive and inferential statistical analysis will be performed using R Studio statistical software. The findings from this evaluation will be shared with hospital administrators and relevant national policymakers and may be used by the Ministry of Health in deciding to expand this approach to other hospitals. The expected results of this research include the development of standard operating guidelines for the creation, distribution, and use of a quarterly syndromic antibiogram for antibiotic decision making that is informed by local epidemiology. Findings from this study will be used to develop a larger multi-site trial in Mozambique.
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Antibacterianos , Ciencia de la Implementación , Humanos , Mozambique/epidemiología , Antibacterianos/uso terapéutico , Niño , Niño Hospitalizado , Pruebas de Sensibilidad Microbiana , Lactante , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Preescolar , Prescripciones de Medicamentos/estadística & datos numéricosRESUMEN
The global spread of infectious diseases caused by pathogenic bacteria significantly poses public health concerns, and methods for sensitive, selective, and facile diagnosis of bacteria can efficiently prevent deterioration and further spreading of the infections. The advent of nanozymes has broadened the spectrum of alternatives for diagnosing bacterial infections. Compared to natural enzymes, nanozymes exhibit the same enzymatic characteristics but offer greater economic efficiency, enhanced durability, and adjustable dimensions. The importance of early diagnosis of bacterial infection and conventional diagnostic approaches is introduced. Subsequently, the review elucidates the definition, properties, and catalytic mechanism of nanozymes. Eventually, the detailed application of nanozymes in detecting bacteria is explored, highlighting their utilization as biosensors that allow for accelerated and highly sensitive identification of bacterial infections and reflecting on the potential of nanozyme-based bacterial detection as a point-of-care testing (POCT) tool. A brief summary of obstacles and future perspectives in this field is presented at the conclusion of this review.
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Infecciones Bacterianas , Técnicas Biosensibles , Pruebas en el Punto de Atención , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiología , Humanos , Técnicas Biosensibles/métodos , Bacterias/aislamiento & purificación , Nanoestructuras/química , CatálisisRESUMEN
While viruses are considered the most common infectious triggers for cytokine storm syndromes (CSS), a growing list of bacterial pathogens, particularly intracellular organisms, have been frequently reported to be associated with this syndrome. Both familial and sporadic cases of CSS are often precipitated by acute infections. It is also important to note that an underlying precipitating infection might not be clinically obvious as the CSS clinical picture can mimic an infectious process or an overwhelming septicemia. It is important to detect such an underlying treatable condition. In addition, infections can also be acquired during the course of CSS due to the concurrent immune suppression with treatment. Optimal CSS outcomes require treating bacterial infections when recognized.CSS should always be suspected in patients presenting with a sepsis-like or multi-organ dysfunction picture. There are many criteria proposed to diagnose CSS in general, with HLH-2004 being the most commonly used. Alternatively, criteria have been proposed for CSS occurring in specific underlying conditions such as systemic lupus erythematosus (SLE) or systemic juvenile idiopathic arthritis (sJIA). However, waiting for many of these criteria to be fulfilled could lead to significant delay in diagnosis, and the physician needs a high index of suspicion for CSS in critically ill febrile hospitalized patients in order to properly recognize the condition. Thus, there should be diagnostic equipoise between CSS and infections, including bacterial, in this population. In this chapter, we discuss the more common bacterial precipitants of CSS with many of the cases being discussed in the pediatric age group.
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Infecciones Bacterianas , Síndrome de Liberación de Citoquinas , Humanos , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/diagnóstico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/complicaciones , Citocinas/metabolismoRESUMEN
Bacterial antibiotic resistance has been recognized as a global threat to public health. It challenges the antibiotics currently used in clinical practice and causes severe and often fatal infectious diseases. Fighting against antibiotic-resistant bacteria (ARB) is growing more urgent. While understanding the molecular mechanisms that underlie resistance is a prerequisite, several major mechanisms have been previously proposed including bacterial efflux systems, reduced cell membrane permeability, antibiotic inactivation by enzymes, target modification, and target protection. In this context, this review presents a panel of promising and potential strategies to combat antibiotic resistance/resistant bacteria. Different types of direct-acting and indirect resistance breakers, such as efflux pump inhibitors, antibiotic adjuvants, and oxidative treatments are discussed. In addition, the emerging multi-omics approaches for rapid resistance identification and promising alternatives to existing antibiotics are highlighted. Overall, this review suggests that continued effort and investment in research are required to develop new antibiotics and alternatives to existing antibiotics and translate them into environmental and clinical applications.
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Antibacterianos , Bacterias , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/genética , Humanos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genéticaRESUMEN
The emergence of antimicrobic-resistant infectious pathogens and the consequent rising in the incidence and prevalence of demises caused by or associated to infections which are not sensitive to drug treatments is one of today's major global health challenges. Antimicrobial resistance (AMR) can bring to therapeutic failure, infection's persistence and risk of serious illness, in particular in vulnerable populations such as the elderly, patients with neoplastic diseases or the immunocompromised. It is assessed that AMR will induce until 10 million deaths per year by 2050, becoming the leading cause of disease-related deaths. The World Health Organisation (WHO) and the United Nations General Assembly urgently call for new measures to combat the phenomenon. Research and development of new antimicrobial agents has decreased due to market failure. However, promising results are coming from new alternative therapeutic strategies such as monoclonal antibodies, microbiome modulators, nanomaterial-based therapeutics, vaccines, and phages. This narrative review aimed to analyse the benefits and weaknesses of alternative therapeutic strategies to antibiotics which treat multidrug-resistant bacterial infections.
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Antibacterianos , Farmacorresistencia Bacteriana Múltiple , Humanos , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Animales , Anticuerpos Monoclonales/uso terapéutico , Bacterias/efectos de los fármacosRESUMEN
The emergence of antimicrobial resistance (AMR) in clinical microbes has led to a search for novel antibiotics for combating bacterial infections. The treatment of bacterial infections becomes more challenging with the onset of biofilm formation. AMR is further accelerated by biofilm physiology and differential gene expression in bacteria with an inherent resistance to conventional antibiotics. In the search for innovative strategies to control the spread of AMR in clinical isolates, plant-derived therapeutic metabolites can be repurposed to control biofilm-associated drug resistance. Unlike antibiotics, designed to act on a single cellular process, phytochemicals can simultaneously target multiple cellular components. Furthermore, they can disrupt biofilm formation and inhibit quorum sensing, offering a comprehensive approach to combat bacterial infections. In bacterial biofilms, the first line of AMR is due to biofilms associated with the extracellular matrix, diffusion barriers, quorum sensing, and persister cells. These extracellular barriers can be overcome using phytochemical-based antibiotic adjuvants to increase the efficacy of antibiotic treatment and restrict the spread of AMR. Furthermore, phytochemicals can be used to target bacterial intracellular machinery such as DNA replication, protein synthesis, efflux pumps, and degrading enzymes. In parallel with pristine phytochemicals, phyto-derived nanomaterials have emerged as an effective means of fighting bacterial biofilms. These nanomaterials can be formulated to cross the biofilm barriers and function on cellular targets. This review focuses on the synergistic effects of phytochemicals and phyto-derived nanomaterials in controlling the progression of biofilm-related AMR. IT provides comprehensive insights into recent advancements and the underlying mechanisms of the use of phyto-derived adjuvants and nanomaterials.
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Antibacterianos , Bacterias , Infecciones Bacterianas , Biopelículas , Nanoestructuras , Fitoquímicos , Percepción de Quorum , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Fitoquímicos/farmacología , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Humanos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana/efectos de los fármacos , Adyuvantes Farmacéuticos/farmacologíaRESUMEN
The zebrafish Danio rerio has become a popular model host to explore disease pathology caused by infectious agents. A main advantage is its transparency at an early age, which enables live imaging of infection dynamics. While multispecies infections are common in patients, the zebrafish model is rarely used to study them, although the model would be ideal for investigating pathogen-pathogen and pathogen-host interactions. This may be due to the absence of an established multispecies infection protocol for a defined organ and the lack of suitable image analysis pipelines for automated image processing. To address these issues, we developed a protocol for establishing and tracking single and multispecies bacterial infections in the inner ear structure (otic vesicle) of the zebrafish by imaging. Subsequently, we generated an image analysis pipeline that involved deep learning for the automated segmentation of the otic vesicle, and scripts for quantifying pathogen frequencies through fluorescence intensity measures. We used Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, three of the difficult-to-treat ESKAPE pathogens, to show that our infection protocol and image analysis pipeline work both for single pathogens and pairwise pathogen combinations. Thus, our protocols provide a comprehensive toolbox for studying single and multispecies infections in real-time in zebrafish.
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Procesamiento de Imagen Asistido por Computador , Pseudomonas aeruginosa , Pez Cebra , Pez Cebra/microbiología , Animales , Procesamiento de Imagen Asistido por Computador/métodos , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/diagnóstico por imagen , Acinetobacter baumannii/patogenicidad , Modelos Animales de Enfermedad , Interacciones Huésped-Patógeno , Klebsiella pneumoniae/patogenicidad , Oído Interno/microbiología , Oído Interno/diagnóstico por imagen , Aprendizaje ProfundoRESUMEN
We report the use of a new multiplex Real-Time PCR platform to simultaneously identify 24 pathogens and 3 antimicrobial-resistance genes directly from respiratory samples of COVID-19 patients. Results were compared to culture-based diagnosis. Secondary infections were detected in 60% of COVID-19 patients by molecular analysis and 73% by microbiological assays, with no significant differences in accuracy, indicating Gram-negative bacteria as the predominant species. Among fungal superinfections, Aspergillus spp. were detected by both methods in more than 7% of COVID-19 patients. Oxacillin-resistant S. aureus and carbapenem-resistant K. pneumoniae were highlighted by both methods. Secondary microbial infections in SARS-CoV-2 patients are associated with poor outcomes and an increased risk of death. Since PCR-based tests significantly reduce the turnaround time to 4 hours and 30 minutes (compared to 48 hours for microbial culture), we strongly support the routine use of molecular techniques, in conjunction with microbiological analysis, to identify co/secondary infections.
Asunto(s)
COVID-19 , Coinfección , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/microbiología , SARS-CoV-2/genética , Coinfección/diagnóstico , Coinfección/microbiología , Coinfección/virología , Masculino , Persona de Mediana Edad , Femenino , Técnicas de Diagnóstico Molecular/métodos , Anciano , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/virología , Reacción en Cadena de la Polimerasa Multiplex/métodos , Adulto , Farmacorresistencia Bacteriana/genética , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/microbiologíaRESUMEN
Development of potent and broad-spectrum antimicrobial peptides (AMPs) could help overcome the antimicrobial resistance crisis. We develop a peptide language-based deep generative framework (deepAMP) for identifying potent, broad-spectrum AMPs. Using deepAMP to reduce antimicrobial resistance and enhance the membrane-disrupting abilities of AMPs, we identify, synthesize, and experimentally test 18 T1-AMP (Tier 1) and 11 T2-AMP (Tier 2) candidates in a two-round design and by employing cross-optimization-validation. More than 90% of the designed AMPs show a better inhibition than penetratin in both Gram-positive (i.e., S. aureus) and Gram-negative bacteria (i.e., K. pneumoniae and P. aeruginosa). T2-9 shows the strongest antibacterial activity, comparable to FDA-approved antibiotics. We show that three AMPs (T1-2, T1-5 and T2-10) significantly reduce resistance to S. aureus compared to ciprofloxacin and are effective against skin wound infection in a female wound mouse model infected with P. aeruginosa. In summary, deepAMP expedites discovery of effective, broad-spectrum AMPs against drug-resistant bacteria.