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Biochemical Pharmacology Jun 2017The history of the first commercial antibiotics is briefly reviewed, together with data from the US and WHO, showing the decrease in death due to infectious diseases... (Review)
Review
The history of the first commercial antibiotics is briefly reviewed, together with data from the US and WHO, showing the decrease in death due to infectious diseases over the 20th century, from just under half of all deaths, to less than 10%. The second half of the 20th century saw the new use of antibiotics as growth promoters for food animals in the human diet, and the end of the 20th century and beginning of the 21st saw the beginning and rapid rise of advanced microbial resistance to antibiotics.
Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Humans; Penicillium
PubMed: 27956111
DOI: 10.1016/j.bcp.2016.12.005 -
Advances in Experimental Medicine and... 2018The rapid evolution of antibiotic resistance in Clostridium difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matter... (Review)
Review
The rapid evolution of antibiotic resistance in Clostridium difficile and the consequent effects on prevention and treatment of C. difficile infections (CDIs) are matter of concern for public health. Antibiotic resistance plays an important role in driving C. difficile epidemiology. Emergence of new types is often associated with the emergence of new resistances and most of epidemic C. difficile clinical isolates is currently resistant to multiple antibiotics. In particular, it is to worth to note the recent identification of strains with reduced susceptibility to the first-line antibiotics for CDI treatment and/or for relapsing infections. Antibiotic resistance in C. difficile has a multifactorial nature. Acquisition of genetic elements and alterations of the antibiotic target sites, as well as other factors, such as variations in the metabolic pathways and biofilm production, contribute to the survival of this pathogen in the presence of antibiotics. Different transfer mechanisms facilitate the spread of mobile elements among C. difficile strains and between C. difficile and other species. Furthermore, recent data indicate that both genetic elements and alterations in the antibiotic targets can be maintained in C. difficile regardless of the burden imposed on fitness, and therefore resistances may persist in C. difficile population in absence of antibiotic selective pressure.
Topics: Anti-Bacterial Agents; Clostridioides difficile; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests
PubMed: 29383668
DOI: 10.1007/978-3-319-72799-8_9 -
The Medical Clinics of North America Sep 2018Antimicrobial stewardship involves optimizing antibiotic use while using cost-effective interventions to minimize antibiotic resistance and control Clostridium... (Review)
Review
Antimicrobial stewardship involves optimizing antibiotic use while using cost-effective interventions to minimize antibiotic resistance and control Clostridium difficile. An effective hospital-wide antimicrobial stewardship program (ASP) should be led by an infectious disease (ID) physician. The ASP team needs full and ongoing financial support for the ASP from the hospital administration. The ID clinician leader should have special expertise in various aspects of antimicrobial therapy, that is, pharmacokinetics, resistance, pharmacoeconomics, and C difficile. The ASP ID team leader and ID-trained clinical pharmacist staff are responsible for customizing ASP interventions to the hospital's unique set of antibiotic use-related concerns.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Stewardship; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Infection Control
PubMed: 30126571
DOI: 10.1016/j.mcna.2018.04.003 -
International Microbiology : the... Nov 2021We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century,... (Review)
Review
We are living in a society of fear, where the objectivity in estimating risks is distorted by the media and the interested parties. During more than half of a century, the feeling of antibiotic resistance as an apocalyptic phenomenon able to push our society to the high mortality rates caused by infectious diseases in the dark pre-antibiotic ages has been steadily rising. However, at the current status of modern medicine, at least in the high-medium income countries, mortality by lack of efficacy of the antibiotic armamentarium in the therapy of infections is a problem, but not a catastrophe. The threat of antibiotic resistance has many other aspects than failures of therapy in the individual patient. Among them, the increase in the frequency of severe and potentially lethal infections, as bacteremia, the population biology alterations of the healthy microbiota, the global acceleration of bacterial evolution by selecting natural genetic tools mediating microbial interactions, and, most importantly, by modifying the equilibrium and composition of environmental microbial communities. All these threats have huge implications for human health as members of a Biosphere entirely rooted in a menaced microbiosphere.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Drug Resistance, Microbial; Humans; Microbiota
PubMed: 34028624
DOI: 10.1007/s10123-021-00184-y -
Drug Development Research Feb 2019Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches... (Review)
Review
Antibiotic resistance, especially in gram-negative bacteria, is spreading globally and rapidly. Development of new antibiotics lags behind; therefore, novel approaches to the problem of antibiotic resistance are sorely needed and this commentary highlights one relatively unexplored target for drug development: conjugation. Conjugation is a common mechanism of horizontal gene transfer in bacteria that is instrumental in the spread of antibiotic resistance among bacteria. Most resistance genes are found on mobile genetic elements and primarily spread by conjugation. Furthermore, conjugative elements can act as a reservoir to maintain antibiotic resistance in the bacterial population even in the absence of antibiotic selection. Thus, conjugation can spread antibiotic resistance quickly between bacteria of the microbiome and pathogens when selective pressure (antibiotics) is introduced. Potential drug targets include the plasmid-encoded conjugation system and the host-encoded proteins important for conjugation. Ideally, a conjugation inhibitor will be used alongside antibiotics to prevent the spread of resistance to or within pathogens while not acting as a growth inhibitor itself. Inhibiting conjugation will be an important addition to our arsenal of strategies to combat the antibiotic resistance crisis, allowing us to extend the usefulness of antibiotics.
Topics: Animals; Anti-Bacterial Agents; Conjugation, Genetic; Drug Resistance, Microbial; Humans; Plasmids
PubMed: 30343487
DOI: 10.1002/ddr.21457 -
Journal of Clinical Pathology Sep 2015Procalcitonin (PCT) is the 116 amino acid precursor of the hormone calcitonin, produced by the C cells of the thyroid. Its synthesis is upregulated in bacterial... (Review)
Review
Procalcitonin (PCT) is the 116 amino acid precursor of the hormone calcitonin, produced by the C cells of the thyroid. Its synthesis is upregulated in bacterial infection and downregulated by viral infection. Consequently, with the increasing development of antibiotic resistance, interest has focused on the ability of this marker to not only diagnose infection but to tailor antibiotic treatment and help reduce the development of antibiotic resistance. The value of PCT depends on the specific clinical situation and pretest probability of disease. This article discusses the role of PCT in these different situations, namely primary care, the emergency department and the intensive care unit. The true cost effectiveness of this test remains difficult to prove as evidence for the potential impact of using PCT on slowing the development of bacterial resistance remains largely circumstantial.
Topics: Animals; Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Drug Resistance, Microbial; Humans; Protein Precursors
PubMed: 26124314
DOI: 10.1136/jclinpath-2014-202807 -
Science (New York, N.Y.) Feb 2022Machine learning can use clinical history to lower the risk of infection recurrence.
Machine learning can use clinical history to lower the risk of infection recurrence.
Topics: Drug Resistance, Microbial; Machine Learning
PubMed: 35201873
DOI: 10.1126/science.abn9969 -
Translational Research : the Journal of... Sep 2020Extensive antibiotic use combined with poor historical drug stewardship practices have created a medical crisis in which once treatable bacterial infections are now... (Review)
Review
Extensive antibiotic use combined with poor historical drug stewardship practices have created a medical crisis in which once treatable bacterial infections are now increasingly unmanageable. To combat this, new antibiotics will need to be developed and safeguarded. An emerging class of antibiotics based upon nuclease-stable antisense technologies has proven valuable in preclinical testing against a variety of bacterial pathogens. This review describes the current state of development of antisense-based antibiotics, the mechanisms thus far employed by these compounds, and possible future avenues of research.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Gene Transfer Techniques; Humans; RNA, Antisense
PubMed: 32522669
DOI: 10.1016/j.trsl.2020.06.001 -
Chemical Communications (Cambridge,... May 2023Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming... (Review)
Review
Antibiotic resistance is an enormous problem that is accountable for over a million deaths annually, with numbers expected to significantly increase over the coming decades. Although some of the underlying causes leading up to antibiotic resistance are well understood, many of the molecular processes involved remain elusive. To better appreciate at a molecular level how resistance emerges, customized chemical biology tools can offer a solution. This Feature Article attempts to provide an overview of the wide variety of tools that have been developed over the last decade, by highlighting some of the more illustrative examples. These include the use of fluorescent, photoaffinity and activatable antibiotics and bacterial components to start to unravel the molecular mechanisms involved in resistance. The antibiotic crisis is an eminent global threat and requires the continuous development of creative chemical tools to dissect and ultimately counteract resistance.
Topics: Drug Resistance, Microbial; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial
PubMed: 37039397
DOI: 10.1039/d3cc00759f -
The Science of the Total Environment Jun 2019Aquatic ecosystems subjected to anthropogenic pressures are places of rapid evolution of microbial communities and likely hotspots for selection and emergence of... (Review)
Review
Aquatic ecosystems subjected to anthropogenic pressures are places of rapid evolution of microbial communities and likely hotspots for selection and emergence of antibiotic resistant bacteria. In urban settings, water quality and the risk of infection are generally assessed in sewers and in effluents of wastewater treatment plants. Physical and chemical parameters as well as the presence of antibiotics, antibiotic-resistant bacteria and genes of resistance are driven by urban activities, with adverse effects on aquatic ecosystems. In this paper we review the environmental pressures exerted on bacterial communities in urban runoff waters and discuss the impact of these settings on antibiotic resistance. Considering the worrisome epidemiology of infectious diseases and estimated mortality due to antimicrobial resistance in the coming decades, there is an urgent need to identify all environmental reservoirs of resistant bacteria and resistance genes to complete our knowledge of the epidemiological cycle and of the dynamics of urban antibiotic resistance.
Topics: Bacteria; Cities; Drug Resistance, Bacterial; Drug Resistance, Microbial; Microbiota; Wastewater
PubMed: 30826682
DOI: 10.1016/j.scitotenv.2019.02.183