# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9733 | 0 | 0.9876 | The 2018 Garrod Lecture: Preparing for the Black Swans of resistance. The need for governments to encourage antibiotic development is widely agreed, with 'market entry rewards' being suggested. Unless these are to be spread widely-which is unlikely given the $1 billion sums proposed-we should be wary, for this approach is likely to evolve into one of picking, or commissioning, a few 'winners' based on extrapolation of current resistance trends. The hazard to this is that whilst the evolution of resistance has predictable components, notably mutation, it also has completely unpredictable ones, contingent upon 'Black Swan' events. These include the escape of 'new' resistance genes from environmental bacteria and the recruitment of these genes by promiscuous mobile elements and epidemic strains. Such events can change the resistance landscape rapidly and unexpectedly, as with the rise of Escherichia coli ST131 with CTX-M ESBLs and the emergence of 'impossible' VRE. Given such unpredictability, we simply cannot say with any certainty, for example, which of the four current approaches to combating MBLs offers the best prospect of sustainable prizeworthy success. Only time will tell, though it is encouraging that multiple potential approaches to overcoming these problematic enzymes are being pursued. Rather than seeking to pick winners, governments should aim to reduce development barriers, as with recent relaxation of trial regulations. In particular, once β-lactamase inhibitors have been successfully trialled with one partner drug, there is scope to facilitate licensing them for partnering with other established β-lactams, thereby insuring against new emerging resistance. | 2018 | 30351434 |
| 3754 | 1 | 0.9865 | Cancer departments as a source of resistant bacteria and fungi? Antimicrobial resistance increases worldwide. Among many factors, such as clonal spread of genes of resistance among and intra species, local epidemiology, nosocomial transmission, also consumption of antimicrobials may be responsible. Cancer departments, mainly in centers treating hematologic malignancies and organizing bone marrow transplantation (BMT) are known to have extensive consumption of either prophylactically or therapeutically administered antibiotics and antifungals. It is worthy to remember, that first strains of quinolone resistant E. coli, vancomycin resistant enterococci and staphylococci and fluconazol-resistant Candida albicans appeared in the patients treated for cancer with antineoplastic chemotherapy, resulting in profound granulocytopenia. Therefore, assessment of risks of antibiotic prophylaxis with quinolones and azoles and extensive use of empiric therapy with glycopeptides and polyenes needs to be considered. Intensive prophylactic strategies should be limited to group of high risk, leukemic patients or BMT recipients. | 1999 | 10355526 |
| 8239 | 2 | 0.9864 | Surviving bacterial sibling rivalry: inducible and reversible phenotypic switching in Paenibacillus dendritiformis. Natural habitats vary in available nutrients and room for bacteria to grow, but successful colonization can lead to overcrowding and stress. Here we show that competing sibling colonies of Paenibacillus dendritiformis bacteria survive overcrowding by switching between two distinct vegetative phenotypes, motile rods and immotile cocci. Growing colonies of the rod-shaped bacteria produce a toxic protein, Slf, which kills cells of encroaching sibling colonies. However, sublethal concentrations of Slf induce some of the rods to switch to Slf-resistant cocci, which have distinct metabolic and resistance profiles, including resistance to cell wall antibiotics. Unlike dormant spores of P. dendritiformis, the cocci replicate. If cocci encounter conditions that favor rods, they secrete a signaling molecule that induces a switch to rods. Thus, in contrast to persister cells, P. dendritiformis bacteria adapt to changing environmental conditions by inducible and reversible phenotypic switching. IMPORTANCE: In favorable environments, species may face space and nutrient limits due to overcrowding. Bacteria provide an excellent model for analyzing principles underlying overcrowding and regulation of density in nature, since their population dynamics can be easily and accurately assessed under controlled conditions. We describe a newly discovered mechanism for survival of a bacterial population during overcrowding. When competing with sibling colonies, Paenibacillus dendritiformis produces a lethal protein (Slf) that kills cells at the interface of encroaching colonies. Slf also induces a small proportion of the cells to switch from motile, rod-shaped cells to nonmotile, Slf-resistant, vegetative cocci. When crowding is reduced and nutrients are no longer limiting, the bacteria produce a signal that induces cocci to switch back to motile rods, allowing the population to spread. Genes encoding components of this phenotypic switching pathway are widespread among bacterial species, suggesting that this survival mechanism is not unique to P. dendritiformis. | 2011 | 21628502 |
| 1820 | 3 | 0.9862 | Intensive farming as a source of bacterial resistance to antimicrobial agents in sedentary and migratory vultures: Implications for local and transboundary spread. The role of wild birds in the carriage and transmission of human and food animal bacteria with resistant genotypes has repeatedly been highlighted. However, few studies have focussed on the specific exposure sources and places of acquisition and selection for antimicrobial-resistant bacteria in vultures relying on livestock carcasses across large areas and different continents. The occurrence of bacterial resistance to antimicrobial agents was assessed in the faecal microbiota of sedentary Griffon vultures (Gyps fulvus) and trans-Saharan migratory Egyptian vultures (Neophron percnopterus) in central Spain. High rates (generally >50%) of resistant Escherichia coli and other enterobacteria to amoxicillin, cotrimoxazole and tetracycline were found. About 25-30% of samples were colonised by extended-spectrum beta-lactamases (ESBL) producing bacteria, while 5-17% were positive for plasmid mediated quinolone resistance (PMQR) phenotypes, depending on vulture species and age. In total, nine ESBL types were recorded (7 in griffon vultures and 5 in Egyptian vultures), with CTX-M-1 the most prevalent in both species. The most prevalent PMQR was mediated by qnrS genes. We found no clear differences in the occurrence of antimicrobial resistance in adult vultures of each species, or between nestling and adult Egyptian vultures. This supports the hypothesis that antimicrobial resistance is acquired in the European breeding areas of both species. Bacterial resistance can directly be driven by the regular ingestion of multiple active antimicrobials found in medicated livestock carcasses from factory farms, which should be not neglected as a contributor to the emergence of novel resistance clones. The One Health framework should consider the potential transboundary carriage and spread of epidemic resistance from high-income European to low-income African countries via migratory birds. | 2020 | 32758969 |
| 4899 | 4 | 0.9862 | Chemiluminescent Carbapenem-Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria. Carbapenemase-producing organisms (CPOs) pose a severe threat to antibacterial treatment due to the acquisition of antibiotic resistance. This resistance can be largely attributed to the antibiotic-hydrolyzing enzymes that the bacteria produce. Current carbapenem "wonder drugs", such as doripenem, ertapenem, meropenem, imipenem, and so on, are resistant to regular β-lactamases, but susceptible to carbapenemases. Even worse, extended exposure of bacteria to these drugs accelerates the spread of resistance genes. In order to preserve the clinical efficacy of antibacterial treatment, carbapenem drugs should be carefully regulated and deployed only in cases of a CPO infection. Early diagnosis is therefore of paramount importance. Herein, we report the design, synthesis, and activity of the first carbapenemase-sensitive chemiluminescent probe, CPCL, which may be used to monitor CPO activity. The design of our probe enables enzymatic cleavage of the carbapenem core, which is followed by a facile 1,8-elimination process and the emission of green light through rapid chemical excitation. We have demonstrated the ability of the probe to detect a number of clinically relevant carbapenemases and the successful identification of CPO present in bacterial cultures, such as those used for clinical diagnosis. We believe that our use of "turn-on" chemiluminescence activation will find significant application in future diagnostic assays and improve antibacterial treatment. | 2020 | 31957167 |
| 5070 | 5 | 0.9862 | Sequence-specific DNA solid-phase extraction in an on-chip monolith: Towards detection of antibiotic resistance genes. Antibiotic resistance of bacteria is a growing problem and presents a challenge for prompt treatment in patients with sepsis. Currently used methods rely on culturing or amplification; however, these steps are either time consuming or suffer from interference issues. A microfluidic device was made from black polypropylene, with a monolithic column modified with a capture oligonucleotide for sequence selective solid-phase extraction of a complementary target from a lysate sample. Porous properties of the monolith allow flow and hybridization of a target complementary to the probe immobilized on the column surface. Good flow-through properties enable extraction of a 100μL sample and elution of target DNA in 12min total time. Using a fluorescently labeled target oligonucleotide related to Verona Integron-Mediated Metallo-β-lactamase it was possible to extract and detect a 1pM sample with 83% recovery. Temperature-mediated elution by heating above the duplex melting point provides a clean extract without any agents that interfere with base pairing, allowing various labeling methods or further downstream processing of the eluent. Further integration of this extraction module with a system for isolation and lysis of bacteria from blood, as well as combining with single-molecule detection should allow rapid determination of antibiotic resistance. | 2017 | 28734608 |
| 2554 | 6 | 0.9862 | Development of an antibiotic resistance monitoring system in Hungary. Because of the rapid development and spread of antimicrobial resistance it is important that a system be established to monitor antimicrobial resistance in pathogenic zoonotic and commensal bacteria of animal origin. Susceptibility testing of bacteria from carcasses and different samples of animal origin has been carried out in veterinary institutes for a long time but by an inconsistent methodology. The disc diffusion method proposed by the National Committee for Clinical Laboratory Standards (NCCLS) was introduced in all institutes in 1997. In order to obtain a coherent view of the antimicrobial resistance of bacteria a computer system was consulted, consisting of a central computer to store all data and some local computers attached to it through the network. At these local measuring stations computers are connected to a video camera, which displays the picture of Petri dishes on the monitor, and inhibition zone diameters of bacteria can be drawn with the mouse by the inspector. The software measures the diameters, evaluates whether or not the bacteria are sensitive, and stores the data. The evaluation is based upon the data of the NCCLS. The central computer can be connected to as many local computers with measuring stations as we wish, so it is suitable for an integrated system for monitoring trends in antimicrobial resistance of bacteria from animals, food and humans, facilitating comparison of the occurrence of resistance for each circumstance in the chain. It depends on the examiners which antibiotics they want to examine. Thirty-two different antibiotic panels were compiled, taking into consideration the active ingredients of medicinal products permitted for veterinary use in Hungary, natural resistance and cross-resistance, the mechanism of resistance and the animal species, i.e. which drugs were recommended for treatment in the given animal species, and the recommendations of the OIE Expert Group on Antimicrobial Resistance. The members of the panels can be changed any time, even during the measuring process. In addition to the inhibition zone diameters of bacteria the database also includes information about bacterial and animal species, the age of animals and the sample or organ where the bacteria are from. Since January 2001 the antibiotic susceptibility of E. coli, Salmonella, Campylobacter and Enterococcus strains isolated from the colons of slaughter cows, pigs and broiler chickens has also been examined. Each of the 19 counties of Hungary submits to the laboratory three tied colon samples from a herd of the above-mentioned animals every month. | 2002 | 12113174 |
| 9734 | 7 | 0.9860 | Combination of genetically diverse Pseudomonas phages enhances the cocktail efficiency against bacteria. Phage treatment has been used as an alternative to antibiotics since the early 1900s. However, bacteria may acquire phage resistance quickly, limiting the use of phage treatment. The combination of genetically diverse phages displaying distinct replication machinery in phage cocktails has therefore become a novel strategy to improve therapeutic outcomes. Here, we isolated and studied lytic phages (SPA01 and SPA05) that infect a wide range of clinical Pseudomonas aeruginosa isolates. These relatively small myophages have around 93 kbp genomes with no undesirable genes, have a 30-min latent period, and reproduce a relatively high number of progenies, ranging from 218 to 240 PFU per infected cell. Even though both phages lyse their hosts within 4 h, phage-resistant bacteria emerge during the treatment. Considering SPA01-resistant bacteria cross-resist phage SPA05 and vice versa, combining SPA01 and SPA05 for a cocktail would be ineffective. According to the decreased adsorption rate of the phages in the resistant isolates, one of the anti-phage mechanisms may occur through modification of phage receptors on the target cells. All resistant isolates, however, are susceptible to nucleus-forming jumbophages (PhiKZ and PhiPA3), which are genetically distinct from phages SPA01 and SPA05, suggesting that the jumbophages recognize a different receptor during phage entry. The combination of these phages with the jumbophage PhiKZ outperforms other tested combinations in terms of bactericidal activity and effectively suppresses the emergence of phage resistance. This finding reveals the effectiveness of the diverse phage-composed cocktail for reducing bacterial growth and prolonging the evolution of phage resistance. | 2023 | 37264114 |
| 8203 | 8 | 0.9860 | Intercalated cell function, kidney innate immunity, and urinary tract infections. Intercalated cells (ICs) in the kidney collecting duct have a versatile role in acid-base and electrolyte regulation along with the host immune defense. Located in the terminal kidney tubule segment, ICs are among the first kidney cells to encounter bacteria when bacteria ascend from the bladder into the kidney. ICs have developed several mechanisms to combat bacterial infections of the kidneys. For example, ICs produce antimicrobial peptides (AMPs), which have direct bactericidal activity, and in many cases are upregulated in response to infections. Some AMP genes with IC-specific kidney expression are multiallelic, and having more copies of the gene confers increased resistance to bacterial infections of the kidney and urinary tract. Similarly, studies in human children demonstrate that those with history of UTIs are more likely to have single-nucleotide polymorphisms in IC-expressed AMP genes that impair the AMP's bactericidal activity. In murine models, depleted or impaired ICs result in decreased clearance of bacterial load following transurethral challenge with uropathogenic E. coli. A 2021 study demonstrated that ICs even act as phagocytes and acidify bacteria within phagolysosomes. Several immune signaling pathways have been identified in ICs which may represent future therapeutic targets in managing kidney infections or inflammation. This review's objective is to highlight IC structure and function with an emphasis on current knowledge of IC's diverse innate immune capabilities. | 2024 | 38227050 |
| 6650 | 9 | 0.9860 | Antibiotic resistance is never going to go away. No matter how many drugs we throw at it, no matter how much money and resources are sacrificed to wage a war on resistance, it will always prevail. Humans are forced to coexist with the fact of antibiotic resistance. Public health officials, clinicians, and scientists must find effective ways to cope with antibiotic resistant bacteria harmful to humans and animals and to control the development of new types of resistance. The American Academy of Microbiology convened a colloquium October 12–14, 2008, to discuss antibiotic resistance and the factors that influence the development and spread of resistance. Participants, whose areas of expertise included medicine, microbiology, and public health, made specific recommendations for needed research, policy development, a surveillance network, and treatment guidelines. Antibiotic resistance issues specific to the developing world were discussed and recommendations for improvements were made. Each antibiotic is injurious only to a certain segment of the microbial world, so for a given antibacterial there are some species of bacteria that are susceptible and others not. Bacterial species insusceptible to a particular drug are “naturally resistant.” Species that were once sensitive but eventually became resistant to it are said to have “acquired resistance.” It is important to note that “acquired resistance” affects a subset of strains in the entire species; that is why the prevalence of “acquired resistance” in a species is different according to location. Antibiotic resistance, the acquired ability of a pathogen to withstand an antibiotic that kills off its sensitive counterparts, originally arises from random mutations in existing genes or from intact genes that already serve a similar purpose. Exposure to antibiotics and other antimicrobial products, whether in the human body, in animals, or the environment, applies selective pressure that encourages resistance to emerge favoring both “naturally resistant” strains and strains which have “acquired resistance.” Horizontal gene transfer, in which genetic information is passed between microbes, allows resistance determinants to spread within harmless environmental or commensal microorganisms and pathogens, thus creating a reservoir of resistance. Resistance is also spread by the replication of microbes that carry resistance genes, a process that produces genetically identical (or clonal) progeny. Rapid diagnostic methods and surveillance are some of the most valuable tools in preventing the spread of resistance. Access to more rapid diagnostic tests that could determine the causative agent and antibiotic susceptibility of infections would inform better decision making with respect to antibiotic use, help slow the selection of resistant strains in clinical settings, and enable better disease surveillance. A rigorous surveillance network to track the evolution and spread of resistance is also needed and would probably result in significant savings in healthcare. Developing countries face unique challenges when it comes to antibiotic resistance; chief among them may be the wide availability of antibiotics without a prescription and also counterfeit products of dubious quality. Lack of adequate hygiene, poor water quality, and failure to manage human waste also top the list. Recommendations for addressing the problems of widespread resistance in the developing world include: proposals for training and infrastructure capacity building; surveillance programs; greater access to susceptibility testing; government controls on import, manufacture and use; development and use of vaccines; and incentives for pharmaceutical companies to supply drugs to these countries. Controlling antibiotic resistant bacteria and subsequent infections more efficiently necessitates the prudent and responsible use of antibiotics. It is mandatory to prevent the needless use of antibiotics (e.g., viral infections; unnecessary prolonged treatment) and to improve the rapid prescription of appropriate antibiotics to a patient. Delayed or inadequate prescriptions reduce the efficacy of treatment and favor the spread of the infection. Prudent use also applies to veterinary medicine. For example, antibiotics used as “growth promoters” have been banned in Europe and are subject to review in some other countries. There are proven techniques for limiting the spread of resistance, including hand hygiene, but more rapid screening techniques are needed in order to effectively track and prevent spread in clinical settings. The spread of antibiotic resistance on farms and in veterinary hospitals may also be significant and should not be neglected. Research is needed to pursue alternative approaches, including vaccines, antisense therapy, public health initiatives, and others. The important messages about antibiotic resistance are not getting across from scientists and infectious diseases specialists to prescribers, stakeholders, including the public, healthcare providers, and public officials. Innovative and effective communication initiatives are needed, as are carefully tailored messages for each of the stakeholder groups. | 2009 | 32644325 |
| 6651 | 10 | 0.9860 | A complex cyclical One Health pathway drives the emergence and dissemination of antimicrobial resistance. Since their commercialization, scientists have known that antimicrobial use kills or inhibits susceptible bacteria while allowing resistant bacteria to survive and expand. Today there is widespread antimicrobial resistance (AMR), even to antimicrobials of last resort such as the carbapenems, which are reserved for use in life-threatening infections. It is often convenient to assign responsibility for this global health crisis to the users and prescribers of antimicrobials. However, we know that animals never treated with antimicrobials carry clinically relevant AMR bacteria and genes. The causal pathway from bacterial susceptibility to resistance is not simple, and dissemination is cyclical rather than linear. Amplification of AMR occurs in healthcare environments and on farms where frequent exposure to antimicrobials selects for resistant bacterial populations. The recipients of antimicrobial therapy release antimicrobial residues, resistant bacteria, and resistance genes in waste products. These are reduced but not removed during wastewater and manure treatment and enter surface waters, soils, recreational parks, wildlife, and fields where animals graze and crops are grown for human and animal consumption. The cycle is complete when a patient carrying AMR bacteria is treated with antimicrobials that amplify the resistant bacterial populations. Reducing the development and spread of AMR requires a One Health approach with the combined commitment of governments, medical and veterinary professionals, agricultural industries, food and feed processors, and environmental scientists. In this review and in the companion Currents in One Health by Ballash et al, JAVMA, April 2024, we highlight just a few of the steps of the complex cyclical causal pathway that leads to the amplification, dissemination, and maintenance of AMR. | 2024 | 38467112 |
| 9748 | 11 | 0.9859 | Resistance in antimicrobial photodynamic inactivation of bacteria. Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can "escape" more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria. | 2015 | 26098395 |
| 9930 | 12 | 0.9859 | Extended-spectrum beta-lactamases and other enzymes providing resistance to oxyimino-beta-lactams. Bacteria have once again demonstrated their remarkably versatility in meeting the introduction of new classes of beta-lactam antibiotics by modifying available plasmid mediated beta-lactamases to expand their spectrum of action and by incorporating chromosomal beta-lactamase genes onto plasmids that permit their spread to new hosts. Such resistance is more common than presently is appreciated because current NCCLS breakpoints for resistance underestimate its prevalence. A number of risk factors for acquisition of ESBL-producing K. pneumoniae have been defined, but most will be no easier to control than those for infection by MRSA or VRE. More clinical and animal model studies are needed to evaluate options for treatment. Most strains remain susceptible to imipenem and other carbapenems, but carbapenem resistance has appeared either by spread of metallo-beta-lactamase or by production of an AmpC enzyme combined with loss of an outer membrane porin channel. Attack on our adversaries' latest biological weapons is likely to require enhanced versatility on our part as well. | 1997 | 9421705 |
| 4762 | 13 | 0.9859 | The Impact of Harsh Stratospheric Conditions on Survival and Antibiotic Resistance Profile of Non-Spore Forming Multidrug Resistant Human Pathogenic Bacteria Causing Hospital-Associated Infections. Bacteria are constantly being lifted to the stratosphere due to air movements caused by weather phenomena, volcanic eruptions, or human activity. In the upper parts of the atmosphere, they are exposed to extremely harsh and mutagenic conditions such as UV and space radiation or ozone. Most bacteria cannot withstand that stress, but for a fraction of them, it can act as a trigger for selective pressure and rapid evolution. We assessed the impact of stratospheric conditions on the survival and antibiotic resistance profile of common non-spore-forming human pathogenic bacteria, both sensitive and extremely dangerous multidrug-resistant variants, with plasmid-mediated mechanisms of resistance. Pseudomonas aeruginosa did not survive the exposure. In the case of strains that were recovered alive, the survival was extremely low: From 0.00001% of Klebsiella pneumoniae carrying the ndm-1 gene and methicillin-resistant Staphylococcus aureus mecA-positive with reduced susceptibility to vancomycin (MRSA/VISA), to a maximum of 0.001% of K. pneumoniae sensitive to all common antibiotics and S. aureus sensitive to vancomycin (MRSA/VSSA). We noticed a tendency towards increased antibiotic susceptibility after the stratospheric flight. Antimicrobial resistance is a current real, global, and increasing problem, and our results can inform current understandings of antibiotic resistance mechanisms and development in bacteria. | 2023 | 36833485 |
| 6649 | 14 | 0.9858 | The development of antibiotics has provided much success against infectious diseases in animals and humans. But the intensive and extensive use of antibiotics over the years has resulted in the emergence of drug-resistant bacterial pathogens. The existence of a reservoir(s) of antibiotic resistant bacteria and antibiotic resistance genes in an interactive environment of animals, plants, and humans provides the opportunity for further transfer and dissemination of antibiotic resistance. The emergence of antibiotic resistant bacteria has created growing concern about its impact on animal and human health. To specifically address the impact of antibiotic resistance resulting from the use of antibiotics in agriculture, the American Academy of Microbiology convened a colloquium, “Antibiotic Resistance and the Role of Antimicrobials in Agriculture: A Critical Scientific Assessment,” in Santa Fe, New Mexico, November 2–4, 2001. Colloquium participants included academic, industrial, and government researchers with a wide range of expertise, including veterinary medicine, microbiology, food science, pharmacology, and ecology. These scientists were asked to provide their expert opinions on the current status of antibiotic usage and antibiotic resistance, current research information, and provide recommendations for future research needs. The research areas to be addressed were roughly categorized under the following areas: ▪ Origins and reservoirs of resistance; ▪ Transfer of resistance; ▪ Overcoming/modulating resistance by altering usage; and ▪ Interrupting transfer of resistance. The consensus of colloquium participants was that the evaluation of antibiotic usage and its impact were complex and subject to much speculation and polarization. Part of the complexity stems from the diverse array of animals and production practices for food animal production. The overwhelming consensus was that any use of antibiotics creates the possibility for the development of antibiotic resistance, and that there already exist pools of antibiotic resistance genes and antibiotic resistant bacteria. Much discussion revolved around the measurement of antibiotic usage, the measurement of antibiotic resistance, and the ability to evaluate the impact of various types of usage (animal, human) on overall antibiotic resistance. Additionally, many participants identified commensal bacteria as having a possible role in the continuance of antibiotic resistance as reservoirs. Participants agreed that many of the research questions could not be answered completely because of their complexity and the need for better technologies. The concept of the “smoking gun” to indicate that a specific animal source was important in the emergence of certain antibiotic resistant pathogens was discussed, and it was agreed that ascribing ultimate responsibility is likely to be impossible. There was agreement that expanded and more improved surveillance would add to current knowledge. Science-based risk assessments would provide better direction in the future. As far as preventive or intervention activities, colloquium participants reiterated the need for judicious/prudent use guidelines. Yet they also emphasized the need for better dissemination and incorporation by end-users. It is essential that there are studies to measure the impact of educational efforts on antibiotic usage. Other recommendations included alternatives to antibiotics, such as commonly mentioned vaccines and probiotics. There also was an emphasis on management or production practices that might decrease the need for antibiotics. Participants also stressed the need to train new researchers and to interest students in postdoctoral work, through training grants, periodic workshops, and comprehensive conferences. This would provide the expertise needed to address these difficult issues in the future. Finally, the participants noted that scientific societies and professional organizations should play a pivotal role in providing technical advice, distilling and disseminating information to scientists, media, and consumers, and in increasing the visibility and funding for these important issues. The overall conclusion is that antibiotic resistance remains a complex issue with no simple answers. This reinforces the messages from other meetings. The recommendations from this colloquium provide some insightful directions for future research and action. | 2002 | 32687288 |
| 9735 | 15 | 0.9858 | Arms race and fluctuating selection dynamics in Pseudomonas aeruginosa bacteria coevolving with phage OMKO1. Experimental evolution studies have examined coevolutionary dynamics between bacteria and lytic phages, where two models for antagonistic coevolution dominate: arms-race dynamics (ARD) and fluctuating-selection dynamics (FSD). Here, we tested the ability for Pseudomonas aeruginosa to coevolve with phage OMKO1 during 10 passages in the laboratory, whether ARD versus FSD coevolution occurred, and how coevolution affected a predicted phenotypic trade-off between phage resistance and antibiotic sensitivity. We used a unique "deep" sampling design, where 96 bacterial clones per passage were obtained from the three replicate coevolving communities. Next, we examined phenotypic changes in growth ability, susceptibility to phage infection and resistance to antibiotics. Results confirmed that the bacteria and phages coexisted throughout the study with one community undergoing ARD, whereas the other two showed evidence for FSD. Surprisingly, only the ARD bacteria demonstrated the anticipated trade-off. Whole genome sequencing revealed that treatment populations of bacteria accrued more de novo mutations, relative to a control bacterial population. Additionally, coevolved bacteria presented mutations in genes for biosynthesis of flagella, type-IV pilus and lipopolysaccharide, with three mutations fixing contemporaneously with the occurrence of the phenotypic trade-off in the ARD-coevolved bacteria. Our study demonstrates that both ARD and FSD coevolution outcomes are possible in a single interacting bacteria-phage system and that occurrence of predicted phage-driven evolutionary trade-offs may depend on the genetics underlying evolution of phage resistance in bacteria. These results are relevant for the ongoing development of lytic phages, such as OMKO1, in personalized treatment of human patients, as an alternative to antibiotics. | 2022 | 36168737 |
| 6560 | 16 | 0.9858 | Translating antibiotic prescribing into antibiotic resistance in the environment: A hazard characterisation case study. The environment receives antibiotics through a combination of direct application (e.g., aquaculture and fruit production), as well as indirect release through pharmaceutical manufacturing, sewage and animal manure. Antibiotic concentrations in many sewage-impacted rivers are thought to be sufficient to select for antibiotic resistance genes. Yet, because antibiotics are nearly always found associated with antibiotic-resistant faecal bacteria in wastewater, it is difficult to distinguish the selective role of effluent antibiotics within a 'sea' of gut-derived resistance genes. Here we examine the potential for macrolide and fluoroquinolone prescribing in England to select for resistance in the River Thames catchment, England. We show that 64% and 74% of the length of the modelled catchment is chronically exposed to putative resistance-selecting concentrations (PNEC) of macrolides and fluoroquinolones, respectively. Under current macrolide usage, 115 km of the modelled River Thames catchment (8% of total length) exceeds the PNEC by 5-fold. Similarly, under current fluoroquinolone usage, 223 km of the modelled River Thames catchment (16% of total length) exceeds the PNEC by 5-fold. Our results reveal that if reduced prescribing was the sole mitigating measure, that macrolide and fluoroquinolone prescribing would need to decline by 77% and 85%, respectively, to limit resistance selection in the catchment. Significant reductions in antibiotic prescribing are feasible, but innovation in sewage-treatment will be necessary for achieving substantially-reduced antibiotic loads and inactivation of DNA-pollution from resistant bacteria. Greater confidence is needed in current risk-based targets for antibiotics, particularly in mixtures, to better inform environmental risk assessments and mitigation. | 2019 | 31483803 |
| 4761 | 17 | 0.9858 | Antimicrobial resistance and biofilm formation of penile prosthesis isolates: insights from in-vitro analysis. BACKGROUND: Inflatable penile prostheses (IPPs) have been shown to harbor biofilms in the presence and absence of infection despite exposure to various antimicrobials. Microbes persisting on IPPs following antibiotic exposure have not been adequately studied to assess biofilm formation capacity and antibiotic resistance. AIM: In this study, we aimed to assess these properties of microbes obtained from explanted infected and non-infected IPPS using an in vitro model. METHODS: 35 bacterial isolates were grown and tested against various single-agent or multiple agent antibiotic regimens including: bacitracin, cefaclor, cefazolin, gentamicin, levofloxacin, trimethoprim-sulfamethoxazole, tobramycin, vancomycin, piperacillin/tazobactam, gentamicin + piperacillin/tazobactam, gentamicin + cefazolin, and gentamicin + vancomycin. Zones of inhibition were averaged for each sample site and species. Statistics were analyzed with Holm's corrected, one-sample t-tests against a null hypothesis of 0. Isolates were also allowed to form biofilms in a 96-well polyvinyl plate and absorbance was tested at 570 nm using a microplate reader. OUTCOMES: Resistance was determined via clinical guidelines or previously established literature, and the mean and standard deviation of biofilm absorbance values were calculated and normalized to the optical density600 of the bacterial inoculum. RESULTS: Every species tested was able to form robust biofilms with the exception of Staphylococcus warneri. As expected, most bacteria were resistant to common perioperative antimicrobial prophylaxis. Gentamicin dual therapy demonstrated somewhat greater efficacy. STRENGTHS AND LIMITATIONS: This study examines a broad range of antimicrobials against clinically obtained bacterial isolates. However, not all species and antibiotics tested had standardized breakpoints, requiring the use of surrogate values from the literature. The microbes included in this study and their resistance genes are expectedly biased towards those that survived antibiotic exposure, and thus reflect the types of microbes which might "survive" in vivo exposure following revisional surgery. CLINICAL TRANSLATION: Despite exposure to antimicrobials, bacteria isolated during penile prosthesis revision for both infected and non-infected cases exhibit biofilm forming capacity and extensive antibiotic resistance patterns in vitro. These microbes merit further investigation to understand when simple colonization vs re-infection might occur. CONCLUSIONS: Although increasing evidence supports the concept that all IPPs harbor biofilms, even in the absence of infection, a deeper understanding of the characteristics of bacteria that survive revisional surgery is warranted. This study demonstrated extensive biofilm forming capabilities, and resistance patterns among bacteria isolated from both non-infected and infected IPP revision surgeries. Further investigation is warranted to determine why some devices become infected while others remain colonized but non-infected. | 2025 | 40062463 |
| 4852 | 18 | 0.9858 | Recent trends in antibiotic resistance in European ICUs. PURPOSE OF REVIEW: Antimicrobial resistance is an emerging problem in ICUs worldwide. As numbers of published results from national/international surveillance studies rise rapidly, the amount of new information may be overwhelming. Therefore, we reviewed recent trends in antibiotic resistance in ICUs across Europe in the past 18 months. RECENT FINDINGS: In this period, infections caused by methicillin-resistant Staphylococcus aureus appeared to stabilize (and even decrease) in some countries, and infection rates due to Gram-positive bacteria resistant to vancomycin, linezolid or daptomycin have remained low. In contrast, we are witnessing a continent-wide emergence of infections caused by multiresistant Gram-negative bacteria, especially Escherichia coli and Klebsiella pneumoniae, with easily exchangeable resistance genes located on plasmids, producing enzymes such as extended spectrum β-lactamases and carbapenamases. In the absence of new antibiotics, prevention of infections, reducing unnecessary antibiotic use, optimizing adherence to universal hygienic and infection control measures, and improving implementation of diagnostic tests are our only tools to combat this threat. SUMMARY: As the epidemiology of antibiotic resistance in ICUs is rapidly changing toward more frequently occurring epidemics and endemicity of multi and panresistant Gram-negative pathogens, better infection control and improved diagnostics will become even more important than before. | 2011 | 21986462 |
| 4791 | 19 | 0.9858 | Detection of tetracycline resistance genes by PCR methods. Rapid, accurate, and sensitive determination of antibiotic resistance profiles of various human and animal pathogens becomes a vital prerequisite for successful therapeutic intervention in the face of the increased occurrences of drug-resistant bacterial infections. The current methods, which are dependent on cultivation of pathogens and phenotypic expression of antibiotic resistance, usually require excessive time, special microbiological equipment, and qualified personnel. However, even with all these requisites, for example, no bacteria can be grown from more than 80% of all clinical samples sent to clinical microbiology laboratories. Besides the cultivation limitations, the cultivation-based determination of an antibiotic resistance profile lacks the genotypic information, which is essential for understanding the epidemiology and routes of transmission of antibiotic resistance genes. These genes often reside on mobile genetic elements and can move freely between commensal and pathogenic microbiota, occurring even between taxonomically distant clinical and environmental microbiota. Therefore, development of genotyping methods for detection of antibiotic resistance genes is highly desirable for fast, accurate, and sensitive detection of antibiotic resistance genes in a broad range of pathogenic and commensal bacteria in both clinical and environmental samples. As a model for our studies we have chosen the genes conferring resistance to tetracyclines. Tetracyclines belong to a family of broad-spectrum antibiotics that include tetracycline, chlortetracycline, oxytetracycline, demeclocycline, methacycline, doxycycline, minocycline, and a number of other semisynthetic derivatives. These antibiotics inhibit protein synthesis in Gram-positive and Gram-negative bacteria by preventing the binding of aminoacyl-tRNA molecules to the 30S ribosomal subunit. The antibiotics of this group were introduced in the late 1950s and since then have been widely used in clinical and veterinary medicine, as well as for prophylaxis and growth promotion in food animals. Because of the possible misuse and overuse of these drugs, resistance to this class of antibiotics is widespread among many clinical isolates, thus limiting the utility of tetracyclines in treating infections. Despite this shortcoming, antibiotics of this class still remain in the active arsenal for dermatologists to treat skin infections such as acne and rosacea. | 2004 | 15156014 |