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British Journal of Biomedical Science 2023Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs... (Review)
Review
Antimicrobial resistance (AMR) has now emerged as a chronic public health problem globally, with the forecast of 10 million deaths per year globally by 2050. AMR occurs when viruses, bacteria, fungi and parasites do not respond to antimicrobial treatments in humans and animals, thus allowing the survival of the microorganism within the host. The prominent cause contributing to the current crisis remains to be the overuse and misuse of antimicrobials, particularly the inappropriate usage of antibiotics, increasing the global burden of antimicrobial resistance. The global consumption and usage of antibiotics are therefore closely monitored at all times. This review provides a current overview of the implications of strategies used by international governmental organisations, including the UN's 17 Sustainable Development Goals (SDGs), to address the problem of antibiotic resistance, as well as the "," a system incorporating a multidisciplinary effort to achieve the best possible health outcome by acknowledging the clear connections between humans, animals and their shared environment. The importance of public awareness and health literacy of lay audiences still needs to be further emphasised as part of global and local action plans. Antimicrobial resistance continues to be a major global public health dilemma of the 21st century. Already this topic is receiving substantial political input from the G7 countries and continues to be on the agenda of numerous political conferences. The consequences of failure to adequately address AMR are profound, with estimations of a return to the pre-antibiotic era, where everyday infections relating to childbirth, surgery and open fractured limbs could be potentially life-threatening. AMR itself represents a microcosm of factors, including social anthropology, civil unrest/war, diasporas, ethnic displacement, political systems, healthcare, economics, societal behaviour both at a population and individual level, health literacy, geoclimatic events, global travel and pharmaceutical innovation and investment, thus finding a solution that adequately addresses AMR and which helps stem further AMR emergence is complicated. Success will involve individuals, communities and nations all working together to ensure that the world continues to possess a sufficient armamentarium of effective antimicrobials that will sustain human and animal health, both now and in the future.
Topics: Animals; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Anti-Infective Agents
PubMed: 37448857
DOI: 10.3389/bjbs.2023.11387 -
Virulence Dec 2023is the most common cause of nosocomial antibiotic-associated diarrhea, and is responsible for a spectrum of diseases characterized by high levels of recurrence,... (Review)
Review
is the most common cause of nosocomial antibiotic-associated diarrhea, and is responsible for a spectrum of diseases characterized by high levels of recurrence, morbidity, and mortality. Treatment is complex, since antibiotics constitute both the main treatment and the major risk factor for infection. Worryingly, resistance to multiple antibiotics is becoming increasingly widespread, leading to the classification of this pathogen as an urgent threat to global health. As a consummate opportunist, is well equipped for promoting disease, owing to its arsenal of virulence factors: transmission of this anaerobe is highly efficient due to the formation of robust endospores, and an array of adhesins promote gut colonization. produces multiple toxins acting upon gut epithelia, resulting in manifestations typical of diarrheal disease, and severe inflammation in a subset of patients. This review focuses on such virulence factors, as well as the importance of antimicrobial resistance and genome plasticity in enabling pathogenesis and persistence of this important pathogen.
Topics: Humans; Virulence; Clostridioides difficile; Clostridioides; Clostridium Infections; Virulence Factors; Diarrhea; Anti-Bacterial Agents
PubMed: 36419222
DOI: 10.1080/21505594.2022.2150452 -
Cell Sep 2023Antimicrobial resistance is a leading mortality factor worldwide. Here, we report the discovery of clovibactin, an antibiotic isolated from uncultured soil bacteria....
Antimicrobial resistance is a leading mortality factor worldwide. Here, we report the discovery of clovibactin, an antibiotic isolated from uncultured soil bacteria. Clovibactin efficiently kills drug-resistant Gram-positive bacterial pathogens without detectable resistance. Using biochemical assays, solid-state nuclear magnetic resonance, and atomic force microscopy, we dissect its mode of action. Clovibactin blocks cell wall synthesis by targeting pyrophosphate of multiple essential peptidoglycan precursors (CPP, lipid II, and lipid III). Clovibactin uses an unusual hydrophobic interface to tightly wrap around pyrophosphate but bypasses the variable structural elements of precursors, accounting for the lack of resistance. Selective and efficient target binding is achieved by the sequestration of precursors into supramolecular fibrils that only form on bacterial membranes that contain lipid-anchored pyrophosphate groups. This potent antibiotic holds the promise of enabling the design of improved therapeutics that kill bacterial pathogens without resistance development.
Topics: Anti-Bacterial Agents; Bacteria; Biological Assay; Diphosphates; Soil Microbiology
PubMed: 37611581
DOI: 10.1016/j.cell.2023.07.038 -
Science Advances Jun 2023In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations...
In the face of the alarming rise in global antimicrobial resistance, only a handful of novel antibiotics have been developed in recent decades, necessitating innovations in therapeutic strategies to fill the void of antibiotic discovery. Here, we established a screening platform mimicking the host milieu to select antibiotic adjuvants and found three catechol-type flavonoids-7,8-dihydroxyflavone, myricetin, and luteolin-prominently potentiating the efficacy of colistin. Further mechanistic analysis demonstrated that these flavonoids are able to disrupt bacterial iron homeostasis through converting ferric iron to ferrous form. The excessive intracellular ferrous iron modulated the membrane charge of bacteria via interfering the two-component system /, thereby promoting the colistin binding and subsequent membrane damage. The potentiation of these flavonoids was further confirmed in an in vivo infection model. Collectively, the current study provided three flavonoids as colistin adjuvant to replenish our arsenals for combating bacterial infections and shed the light on the bacterial iron signaling as a promising target for antibacterial therapies.
Topics: Colistin; Bacterial Proteins; Anti-Bacterial Agents; Bacteria; Iron; Homeostasis
PubMed: 37294761
DOI: 10.1126/sciadv.adg4205 -
Medical Anthropology Quarterly Dec 2023In siloed discussions of antimicrobial resistance, antibiotic use on farms in the Global South has emerged as a key site for intervention. The antibiotic consumption...
In siloed discussions of antimicrobial resistance, antibiotic use on farms in the Global South has emerged as a key site for intervention. The antibiotic consumption targeted is not all consumption, but "irrational" consumption. This concept of irrationality is neither new, nor true, but rather is a long-standing form of maintenance work within global health systems. Via an attention to chickens and the antibiotics farmers use to raise them in the suburbs of Kampala, we suggest that claims of irrationality are a central part of constituting what Tania Li has called the 'deficient subject'. In other words, irrationality, like the chicken and the antibiotic, is itself a humanitarian device that maintains a certain condition of governance where 'Africans' are imagined as being in deficit of rationality and good behavior. Claims of irrationality justify (and mask the political nature of) intervention.
Topics: Animals; Humans; Chickens; Uganda; Anthropology, Medical; Politics; Anti-Bacterial Agents
PubMed: 37703403
DOI: 10.1111/maq.12809 -
Biochimica Et Biophysica Acta.... Oct 2023Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii are amongst the highest priority drug-resistant pathogens, for... (Review)
Review
Gram-negative bacteria, including Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii are amongst the highest priority drug-resistant pathogens, for which new antibiotics are urgently needed. Whilst antibiotic drug development is inherently challenging, this is particularly true for Gram-negative bacteria due to the presence of the outer membrane, a highly selective permeability barrier that prevents the ingress of several classes of antibiotic. This selectivity is largely due to an outer leaflet composed of the glycolipid lipopolysaccharide (LPS), which is essential for the viability of almost all Gram-negative bacteria. This essentiality, coupled with the conservation of the synthetic pathway across species and recent breakthroughs in our understanding of transport and membrane homeostasis has made LPS an attractive target for novel antibiotic drug development. Several different targets have been explored and small molecules developed that show promising activity in vitro. However, these endeavours have met limited success in clinical testing and the polymyxins, discovered more than 70 years ago, remain the only LPS-targeting drugs to enter the clinic thus far. In this review, we will discuss efforts to develop therapeutic inhibitors of LPS synthesis and transport and the reasons for limited success, and explore new developments in understanding polymyxin mode of action and the identification of new analogues with reduced toxicity and enhanced activity.
Topics: Anti-Bacterial Agents; Lipopolysaccharides; Polymyxins; Gram-Negative Bacteria
PubMed: 37268022
DOI: 10.1016/j.bbamcr.2023.119507 -
Otolaryngologia Polska = the Polish... Sep 2023Rhinosinusitis is one of the most frequently diagnosed diseases in patients seeking medical consultation. Sinusitis is a heterogeneous group of diseases and can be acute...
Rhinosinusitis is one of the most frequently diagnosed diseases in patients seeking medical consultation. Sinusitis is a heterogeneous group of diseases and can be acute or chronic. The current state of knowledge on rhinosinusitis is presented in the recommendations of the European Position Paper on Rhinosynusitis and Nasal Polyps 2020 (EPOS 2020). More and more attention is paid to the condition of the microbiota in the context of inflammatory changes in the sinuses. There is also a negative effect of excessively prescribed antibiotics on the increase in bacterial resistance to drugs and significant changes in the disturbance in the composition of the microbiota during antibiotic therapy. Since the most common etiology of acute sinusitis is viral, the use of antibiotics in uncomplicated sinusitis is unjustified. New therapeutic solutions are sought, including the use of herbal medicines. The EPOS 2020 document recommends the use of BNO 1016 in uncomplicated acute rhinosinusitis. New models of treatment also take into account the use of biological drugs, especially in the treatment of chronic rhinosinusitis.
Topics: Humans; Sinusitis; Anti-Bacterial Agents; Microbiota; Nasal Polyps
PubMed: 38032332
DOI: 10.5604/01.3001.0053.8709 -
International Journal of Molecular... Sep 2023Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and... (Review)
Review
Staphylococci are major causes of infections in mammals. Mammals are colonized by diverse staphylococcal species, often with moderate to strong host specificity, and colonization is a common source of infection. Staphylococcal infections of animals not only are of major importance for animal well-being but have considerable economic consequences, such as in the case of staphylococcal mastitis, which costs billions of dollars annually. Furthermore, pet animals can be temporary carriers of strains infectious to humans. Moreover, antimicrobial resistance is a great concern in livestock infections, as there is considerable antibiotic overuse, and resistant strains can be transferred to humans. With the number of working antibiotics continuously becoming smaller due to the concomitant spread of resistant strains, alternative approaches, such as anti-virulence, are increasingly being investigated to treat staphylococcal infections. For this, understanding the virulence mechanisms of animal staphylococcal pathogens is crucial. While many virulence factors have similar functions in humans as animals, there are increasingly frequent reports of host-specific virulence factors and mechanisms. Furthermore, we are only beginning to understand virulence mechanisms in animal-specific staphylococcal pathogens. This review gives an overview of animal infections caused by staphylococci and our knowledge about the virulence mechanisms involved.
Topics: Animals; Female; Humans; Virulence; Staphylococcus; Staphylococcal Infections; Anti-Bacterial Agents; Virulence Factors; Mammals; Microbial Sensitivity Tests
PubMed: 37834035
DOI: 10.3390/ijms241914587 -
Current Opinion in Microbiology Aug 2023Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials... (Review)
Review
Antimicrobial susceptibility testing is the cornerstone of antibiotic treatments. Yet, active drugs are frequently unsuccessful in vivo and most clinical trials investigating antibiotics fail. So far, bacterial survival strategies, other than drug resistance, have been largely ignored. As such, drug tolerance and persisters, allowing bacterial populations to survive during antibiotic treatments, could fill a gap in antibiotic susceptibility testing. Therefore, it remains critical to establish robust and scalable bacterial viability measures and to define the clinical relevance of bacterial survivors across various bacterial infections. If successful, these tools could improve drug design and development to prevent tolerance formation or target bacterial survivors, to ultimately reduce treatment failures and curb resistance evolution.
Topics: Humans; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Drug Resistance, Bacterial; Drug Tolerance
PubMed: 37245488
DOI: 10.1016/j.mib.2023.102328 -
International Journal of Molecular... Jul 2023Despite the declining trend of () prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing... (Review)
Review
Despite the declining trend of () prevalence around the globe, ongoing efforts are still needed to optimize current and future regimens in view of the increasing antibiotic resistance. The resistance of to different antibiotics is caused by different molecular mechanisms, and advancements in sequencing technology have come a far way in broadening our understanding and in facilitating the testing of antibiotic susceptibility to . In this literature review, we give an overview of the molecular mechanisms behind resistance, as well as discuss and compare different antibiotic susceptibility tests based on the latest research. We also discuss the principles of antibiotic stewardship and compare the performance of empirical therapies based on up-to-date resistance patterns and susceptibility-guided therapies in providing effective treatment. Studies and clinical guidelines should ensure that the treatment being tested or recommended can reliably achieve a pre-agreed acceptable level of eradication rate and take into account the variations in antibiotic resistance across populations. Local, regional and international organizations must work together to establish routine antibiotic susceptibility surveillance programs and enforce antibiotic stewardship in the treatment of , so that it can be managed in a sustainable and efficient manner.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Drug Resistance, Bacterial; Drug Therapy, Combination; Anti-Bacterial Agents; Clarithromycin
PubMed: 37511471
DOI: 10.3390/ijms241411708