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EMBO Molecular Medicine Jul 2022Bacteriophages (phages) are selective viral predators of bacteria. Abundant and ubiquitous in nature, phages can be used to treat bacterial infections (phage therapy),... (Review)
Review
Bacteriophages (phages) are selective viral predators of bacteria. Abundant and ubiquitous in nature, phages can be used to treat bacterial infections (phage therapy), including refractory infections and those resistant to antibiotics. However, despite an abundance of anecdotal evidence of efficacy, significant hurdles remain before routine implementation of phage therapy into medical practice, including a dearth of robust clinical trial data. Phage-bacterium interactions are complex and diverse, characterized by co-evolution trajectories that are significantly influenced by the environments in which they occur (mammalian body sites, water, soil, etc.). An understanding of the molecular mechanisms underpinning these dynamics is essential for successful clinical translation. This review aims to cover key aspects of bacterium-phage interactions that affect bacterial killing by describing the most relevant published literature and detailing the current knowledge gaps most likely to influence therapeutic success.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Mammals; Phage Therapy
PubMed: 35620963
DOI: 10.15252/emmm.202012435 -
Applied Microbiology and Biotechnology Aug 2016Persisters-a drug-tolerant sub-population in an isogenic bacterial culture-have been featured throughout the last decade due to their important role in recurrent... (Review)
Review
Persisters-a drug-tolerant sub-population in an isogenic bacterial culture-have been featured throughout the last decade due to their important role in recurrent bacterial infections. Numerous investigations detail the mechanisms responsible for the formation of persisters and suggest exciting strategies for their eradication. In this review, we argue that the very term "persistence" is currently used to describe a large and heterogeneous set of physiological phenomena that are functions of bacterial species, strains, growth conditions, and antibiotics used in the experiments. We caution against the oversimplification of the mechanisms of persistence and urge for a more rigorous validation of the applicability of these mechanisms in each case.
Topics: Anti-Bacterial Agents; Bacterial Infections; Biofilms; Drug Resistance, Multiple, Bacterial; Recurrence
PubMed: 27262568
DOI: 10.1007/s00253-016-7648-8 -
Revista Espanola de Quimioterapia :... May 2019Due to the increase in antimicrobial resistance, strategies such as antimicrobial stewardship programs (ASP) have been developed to improve the clinical results,... (Review)
Review
Due to the increase in antimicrobial resistance, strategies such as antimicrobial stewardship programs (ASP) have been developed to improve the clinical results, decrease the adverse effects and the development of resistances and ensure cost-effective therapies. Fosfomycin has a unique mechanism of action against Gram-positive and Gram-negative bacteria. Cross-resistance is uncommon; however, fosfomycin should be used in combination in severe infections to avoid selecting resistant mutations. Fosfomycin's oral formulation facilitates sequential treatment, has low toxicity and high tissue penetration, even in the central nervous system and bone. Fosfomycin is active against resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin- resistant enterococci and penicillin-resistant Streptococcus pneumoniae, as well as against resistant Gram-negative bacteria such as extended-spectrum beta-lactamase-producing and carbapenemase-producing enterobacteria. Fosfomycin is therefore useful for cases of persistent bacteremia, skin and soft tissue infections, as a glycopeptide-sparing and carbapenem-sparing drug for healthcare-associated infections and for polymicrobial infections. Published studies have demonstrated the synergy between fosfomycin and beta-lactams, daptomycin and glycopeptides against MSSA and MRSA; with linezolid in biofilm-associated infections and with aminoglycosides and colistin against Gram-negative bacteria, providing a nephroprotective effect.
Topics: Animals; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Drug Resistance, Multiple, Bacterial; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans
PubMed: 31131594
DOI: No ID Found -
Drug Discovery Today Sep 2021A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&D) efforts, with only... (Review)
Review
A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&D) efforts, with only incremental improvements on existing broad-spectrum classes coming into clinical use recently. The disappointing returns from this approach have focussed attention on narrower-spectrum antibiotics; such new agents are directed against the pathogen of relevance with the additional benefit of preserving the human microbiome(s). Our knowledge of the gut microbiome and its contribution to health homeostasis increases yearly and suggests that broad-spectrum treatments incur health costs beyond the initial infection. Improved diagnostics, antibiotic stewardship, and the crucial role of the gut microbiome in health indicate targeted agents as a more viable approach for future antibiotic R&D.
Topics: Anti-Bacterial Agents; Bacterial Infections; Dysbiosis; Humans; Microbiota
PubMed: 34329771
DOI: 10.1016/j.drudis.2021.07.016 -
Influenza and Other Respiratory Viruses Sep 2013Influenza-associated bacterial and viral infections are responsible for high levels of morbidity and death during pandemic and seasonal influenza episodes. A review was... (Review)
Review
Influenza-associated bacterial and viral infections are responsible for high levels of morbidity and death during pandemic and seasonal influenza episodes. A review was undertaken to assess and evaluate the incidence, epidemiology, aetiology, clinical importance and impact of bacterial and viral co-infection and secondary infection associated with influenza. A review was carried out of published articles covering bacterial and viral infections associated with pandemic and seasonal influenza between 1918 and 2009 (and published through December 2011) to include both pulmonary and extra-pulmonary infections. While pneumococcal infection remains the predominant cause of bacterial pneumonia, the review highlights the importance of other co- and secondary bacterial and viral infections associated with influenza, and the emergence of newly identified dual infections associated with the 2009 H1N1 pandemic strain. Severe influenza-associated pneumonia is often bacterial and will necessitate antibiotic treatment. In addition to the well-known bacterial causes, less common bacteria such as Legionella pneumophila may also be associated with influenza when new influenza strains emerge. This review should provide clinicians with an overview of the range of bacterial and viral co- or secondary infections that could present with influenza illness.
Topics: Bacterial Infections; Coinfection; Humans; Incidence; Influenza, Human; Prevalence
PubMed: 24034494
DOI: 10.1111/irv.12089 -
Microbiology Spectrum Aug 2016The immunocompromised host is a particularly vulnerable population in whom routine and unusual infections can easily and frequently occur. Prosthetic devices are... (Review)
Review
The immunocompromised host is a particularly vulnerable population in whom routine and unusual infections can easily and frequently occur. Prosthetic devices are commonly used in these patients and the infections associated with those devices present a number of challenges for both the microbiologist and the clinician. Biofilms play a major role in device-related infections, which may contribute to failed attempts to recover organisms from routine culture methods. Moreover, device-related microorganisms can be difficult to eradicate by antibiotic therapy alone. Changes in clinical practice and advances in laboratory diagnostics have provided significant improvements in the detection and accurate diagnosis of device-related infections. Disruption of the bacterial biofilm plays an essential role in recovering the causative agent in culture. Various culture and nucleic acid amplification techniques are more accurate to guide directed treatment regimens. This chapter reviews the performance characteristics of currently available diagnostic assays and summarizes published guidelines, where available, for addressing suspected infected prosthetic devices.
Topics: Bacterial Infections; Bacteriological Techniques; Diagnostic Tests, Routine; Disease Susceptibility; Humans; Immunocompromised Host; Practice Guidelines as Topic; Prosthesis-Related Infections
PubMed: 27726768
DOI: 10.1128/microbiolspec.DMIH2-0004-2015 -
Nature Reviews. Nephrology Aug 2019The prevalence of antimicrobial resistance among many common bacterial pathogens is increasing. The emergence and global dissemination of these antibiotic-resistant... (Review)
Review
The prevalence of antimicrobial resistance among many common bacterial pathogens is increasing. The emergence and global dissemination of these antibiotic-resistant bacteria (ARB) is fuelled by antibiotic selection pressure, inter-organism transmission of resistance determinants, suboptimal infection prevention practices and increasing ease and frequency of international travel, among other factors. Patients with chronic kidney disease, particularly those with end-stage renal disease who require dialysis and/or kidney transplantation, have some of the highest rates of colonization and infection with ARB worldwide. These ARB include methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and several multidrug-resistant Gram-negative organisms. Antimicrobial resistance limits treatment options and increases the risk of infection-related morbidity and mortality. Several new antibiotic agents with activity against some of the most common ARB have been developed, but resistance to these agents is already emerging and highlights the dire need for new treatment options as well as consistent implementation and improvement of basic infection prevention practices. Clinicians involved in the care of patients with renal disease must be familiar with the local epidemiology of ARB, remain vigilant for the emergence of novel resistance patterns and adhere strictly to practices proven to prevent transmission of ARB and other pathogens.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Bacterial; Humans; Kidney Diseases
PubMed: 31086308
DOI: 10.1038/s41581-019-0150-7 -
Frontiers in Immunology 2021
Topics: Animals; Bacteria; Bacterial Infections; Biofilms; Host-Pathogen Interactions; Humans; Immune System; Signal Transduction
PubMed: 34163492
DOI: 10.3389/fimmu.2021.696356 -
Cells Dec 2021Lymphatic vessels permeate tissues around the body, returning fluid from interstitial spaces back to the blood after passage through the lymph nodes, which are important... (Review)
Review
Lymphatic vessels permeate tissues around the body, returning fluid from interstitial spaces back to the blood after passage through the lymph nodes, which are important sites for adaptive responses to all types of pathogens. Involvement of the lymphatics in the pathogenesis of bacterial infections is not well studied. Despite offering an obvious conduit for pathogen spread, the lymphatic system has long been regarded to bar the onward progression of most bacteria. There is little direct data on live virulent bacteria, instead understanding is largely inferred from studies investigating immune responses to viruses or antigens in lymph nodes. Recently, we have demonstrated that extracellular bacterial lymphatic metastasis of virulent strains of drives systemic infection. Accordingly, it is timely to reconsider the role of lymph nodes as absolute barriers to bacterial dissemination in the lymphatics. Here, we summarise the routes and mechanisms by which an increasing variety of bacteria are acknowledged to transit through the lymphatic system, including those that do not necessarily require internalisation by host cells. We discuss the anatomy of the lymphatics and other factors that influence bacterial dissemination, as well as the consequences of underappreciated bacterial lymphatic metastasis on disease and immunity.
Topics: Animals; Bacterial Infections; Extracellular Matrix; Humans; Immunity; Lymphatic Metastasis; Rheology; Virulence
PubMed: 35011595
DOI: 10.3390/cells11010033 -
World Journal of Gastroenterology Mar 2014Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating... (Review)
Review
Viable and non-viable pathological bacterial translocation promote a self-perpetuating circle of dysfunctional immune activation and systemic inflammation facilitating infections and organ failure in advanced cirrhosis. Bacterial infections and sepsis are now recognized as a distinct stage in the natural progression of chronic liver disease as they accelerate organ failure and contribute to the high mortality observed in decompensated cirrhosis. The increasing knowledge of structural, immunological and hemodynamic pathophysiology in advanced cirrhosis has not yet translated into significantly improved outcomes of bacterial infections over the last decades. Therefore, early identification of patients at the highest risk for developing infections and infection-related complications is required to tailor the currently available measures of surveillance, prophylaxis and therapy to the patients in need in order to improve the detrimental outcome of bacterial infections in cirrhosis.
Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Bacterial Translocation; Disease Progression; Hemodynamics; Humans; Inflammation Mediators; Liver Cirrhosis; Risk Factors; Treatment Outcome
PubMed: 24627590
DOI: 10.3748/wjg.v20.i10.2542