-
FEMS Microbiology Reviews Sep 2019Infections of antibiotic-resistant pathogens pose an ever-increasing threat to mankind. The investigation of novel approaches for tackling the antimicrobial resistance... (Review)
Review
Infections of antibiotic-resistant pathogens pose an ever-increasing threat to mankind. The investigation of novel approaches for tackling the antimicrobial resistance crisis must be part of any global response to this problem if an untimely reversion to the pre-penicillin era of medicine is to be avoided. One such promising avenue of research involves so-called antibiotic resistance breakers (ARBs), capable of re-sensitising resistant bacteria to antibiotics. Although some ARBs have previously been employed in the clinical setting, such as the β-lactam inhibitors, we posit that the broader field of ARB research can yet yield a greater diversity of more effective therapeutic agents than have been previously achieved. This review introduces the area of ARB research, summarises the current state of ARB development with emphasis on the various major classes of ARBs currently being investigated and their modes of action, and offers a perspective on the future direction of the field.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Biomedical Research; Clinical Trials as Topic; Drug Discovery; Drug Resistance, Microbial; Humans; Mice; beta-Lactamase Inhibitors
PubMed: 31150547
DOI: 10.1093/femsre/fuz014 -
Environment International Jan 2018Antibiotic resistance is a global health crisis linked to increased, and often unrestricted, antibiotic use in humans and animals. As one of the world's largest... (Review)
Review
Antibiotic resistance is a global health crisis linked to increased, and often unrestricted, antibiotic use in humans and animals. As one of the world's largest producers and consumers of antibiotics, China is witness to some of the most acute symptoms of this crisis. Antibiotics and antibiotic resistance genes (ARGs) are widely distributed in surface water, sewage treatment plant effluent, soils and animal wastes. The emergence and increased prevalence of ARGs in the clinic/hospitals, especially carbapenem-resistant gram negative bacteria, has raised the concern of public health officials. It is important to understand the current state of antibiotic use in China and its relationship to ARG prevalence and diversity in the environment. Here we review these relationships and their relevance to antimicrobial resistance (AMR) trends witnessed in the clinical setting. This review highlights the issues of enrichment and dissemination of ARGs in the environment, and also future needs in mitigating the spread of antibiotic resistance in the environment, particularly under the 'planetary health' perspective, i.e., the systems that sustain or threaten human health.
Topics: Animals; Anti-Bacterial Agents; Bacteria; China; Drug Resistance, Microbial; Genes, Bacterial; Humans; Soil Microbiology; Water Microbiology
PubMed: 29107352
DOI: 10.1016/j.envint.2017.10.016 -
Molecules (Basel, Switzerland) Dec 2020Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools... (Review)
Review
Fluoroquinolones (FQs) are arguably among the most successful antibiotics of recent times. They have enjoyed over 30 years of clinical usage and become essential tools in the armoury of clinical treatments. FQs target the bacterial enzymes DNA gyrase and DNA topoisomerase IV, where they stabilise a covalent enzyme-DNA complex in which the DNA is cleaved in both strands. This leads to cell death and turns out to be a very effective way of killing bacteria. However, resistance to FQs is increasingly problematic, and alternative compounds are urgently needed. Here, we review the mechanisms of action of FQs and discuss the potential pathways leading to cell death. We also discuss quinolone resistance and how quinolone treatment can lead to resistance to non-quinolone antibiotics.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Microbial; Humans; Quinolones
PubMed: 33271787
DOI: 10.3390/molecules25235662 -
The Yale Journal of Biology and Medicine Mar 2017Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of... (Review)
Review
Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s. Looking back at the history of penicillin might help us to relive this journey to find new treatments and antimicrobial agents. This is particularly relevant today as the emergence of multiple drug resistant bacteria poses a global threat, and joint efforts are needed to combat the rise and spread of resistance.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Humans; Penicillins
PubMed: 28356901
DOI: No ID Found -
Proceedings of the National Academy of... Apr 2018Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such...
Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1-34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3-15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth ( = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.
Topics: Anti-Bacterial Agents; Bacterial Infections; Drug Resistance, Microbial; Economics; Health Services Accessibility; Humans
PubMed: 29581252
DOI: 10.1073/pnas.1717295115 -
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 -
Environmental Pollution (Barking, Essex... Sep 2021The prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the microbiome is a major public health concern globally. Many habitats... (Review)
Review
The prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the microbiome is a major public health concern globally. Many habitats in the environment are under threat due to excessive use of antibiotics and evolutionary changes occurring in the resistome. ARB and ARGs from farms, cities and hospitals, wastewater treatment plants (WWTPs) or as water runoffs, may accumulate in water, soil, and air. We present a global picture of the resistome by examining ARG-related papers retrieved from PubMed and published in the last 30 years (1990-2020). Natural Language Processing (NLP) was used to retrieve 496,640 papers, out of which 9374 passed the filtering test and were further analyzed to determine the distribution and diversity of ARG subtypes. The papers revealed seven major antibiotic families together with their respective ARG subtypes in different habitats on six continents. Asia, especially China, had the highest number of ARGs related papers compared to other countries/regions/continents. ARGs belonging to multidrug, glycopeptide, and β-lactam families were the most common in reports from hospitals and sulfonamide and tetracycline families were common in reports from farms, WWTPs, water and soil. We also highlight the 'omics' tools used in resistome research, describe some factors that shape the development of resistome, and suggest future work needed to better understand the resistome. The goal was to show the global nature of ARB and ARGs in order to encourage collaborate research efforts aimed at reducing the negative impacts of antibiotic resistance on the One Health concept.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Drug Resistance, Microbial; Genes, Bacterial; Humans; Tetracycline
PubMed: 34051569
DOI: 10.1016/j.envpol.2021.117402 -
Clinical & Experimental Optometry Mar 2018Treatment of Pseudomonas aeruginosa eye infections often becomes a challenge due to the ability of this bacterium to be resistant to antibiotics via intrinsic and... (Review)
Review
Treatment of Pseudomonas aeruginosa eye infections often becomes a challenge due to the ability of this bacterium to be resistant to antibiotics via intrinsic and acquired mechanisms. Transfer of resistance due to interchangeable genetic elements is an important mechanism for the rapid transfer of antibiotic resistance in this pathogen. As a result, drug-resistant strains are becoming increasingly prevalent worldwide. This review systematically analyses data from recent publications to describe the global prevalence and antibiotic sensitivity of ocular P. aeruginosa. Thirty-seven studies were selected for review from PubMed-based searches using the criteria 'microbial keratitis OR eye infection AND Pseudomonas aeruginosa AND antibiotic resistance' and limiting to papers from 2011 onward, to demonstrate the antibiotic resistance from isolates from around the world. Subsequently, we reviewed the ways in which P. aeruginosa can become resistant to antibiotics. Both the rate of isolation of bacteria in general (79 per cent of cases), and prevalence of P. aeruginosa (68 per cent of all isolates) were highest in contact lens-related microbial keratitis. The average resistance rate to common ocular antibiotics such as ciprofloxacin (9 per cent), gentamicin (22 per cent) and ceftazidime (13 per cent) remained relatively low. However, there were large variations in resistance rates reported in studies from different countries, for example resistance to ciprofloxacin reached up to 33 per cent. We next reviewed the types of mobile genetic elements (MGEs) such as plasmids, integrons and transposons that are frequently associated with drug resistance in P. aeruginosa. MGEs are important for the transmission of resistance to beta-lactams and aminoglycosides and recently have been shown to be potential factors for the transmission of fluoroquinolone resistance. Studies on the molecular mechanisms of resistance transfer in ocular P. aeruginosa have begun to be reported and will provide valuable information on the emergence of new antibiotic resistance and potential to treat resistant strains.
Topics: Corneal Ulcer; Drug Resistance, Microbial; Eye Infections, Bacterial; Humans; Pseudomonas Infections; Pseudomonas aeruginosa
PubMed: 29044738
DOI: 10.1111/cxo.12621 -
ELife Mar 2023The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
The global spread of antibiotic resistance could be due to a number of factors, and not just the overuse of antibiotics in agriculture and medicine as previously thought.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Agriculture
PubMed: 36884273
DOI: 10.7554/eLife.86697 -
British Medical Bulletin Mar 2022Antibiotic resistance raises ethical issues due to the severe and inequitably distributed consequences caused by individual actions and policies.
INTRODUCTION OR BACKGROUND
Antibiotic resistance raises ethical issues due to the severe and inequitably distributed consequences caused by individual actions and policies.
SOURCES OF DATA
Synthesis of ethical, scientific and clinical literature.
AREAS OF AGREEMENT
Ethical analyses have focused on the moral responsibilities of patients to complete antibiotic courses, resistance as a tragedy of the commons and attempts to limit use through antibiotic stewardship.
AREAS OF CONTROVERSY
Each of these analyses has significant limitations and can result in self-defeating or overly narrow implications for policy.
GROWING POINTS
More complex analyses focus on ethical implications of ubiquitous asymptomatic carriage of resistant bacteria, non-linear outcomes within and between patients over time and global variation in resistant disease burdens.
AREAS TIMELY FOR DEVELOPING RESEARCH
Neglected topics include the harms of antibiotic use, including off-target effects on the human microbiome, and the lack of evidence guiding most antibiotic prescription decisions.
Topics: Anti-Bacterial Agents; Drug Resistance, Microbial; Humans; Morals
PubMed: 35136968
DOI: 10.1093/bmb/ldab030