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664900.9856 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.200232687288
376210.9853The epidemiology of antimicrobial resistance and transmission of cutaneous bacterial pathogens in domestic animals. As the primary agents of skin and soft tissue infections in animals, Staphylococcus spp and Pseudomonas aeruginosa are among the most formidable bacterial pathogens encountered by veterinarians. Staphylococci are commensal inhabitants of the surfaces of healthy skin and mucous membranes, which may gain access to deeper cutaneous tissues by circumventing the stratum corneum's barrier function. Compromised barrier function occurs in highly prevalent conditions such as atopic dermatitis, endocrinopathies, and skin trauma. P aeruginosa is an environmental saprophyte that constitutively expresses virulence and antimicrobial resistance genes that promote its success as an animal pathogen. For both organisms, infections of the urinary tract, respiratory tract, joints, central nervous system, and body cavities may occur through ascension along epithelial tracts, penetrating injuries, or hematogenous spread. When treating infections caused by these pathogens, veterinarians now face greater therapeutic challenges and more guarded outcomes for our animal patients because of high rates of predisposing factors for infection and the broad dissemination of antimicrobial resistance genes within these bacterial species. This review considers the history of the rise and expansion of multidrug resistance in staphylococci and P aeruginosa and the current state of knowledge regarding the epidemiologic factors that underly the dissemination of these pathogens across companion animal populations. Given the potential for cross-species and zoonotic transmission of pathogenic strains of these bacteria, and the clear role played by environmental reservoirs and fomites, a one-health perspective is emphasized.202336917615
226720.9852MOLECULAR CHARACTERIZATION AND DETECTION OF MULTIDRUGRESISTANT GENE IN BACTERIAL ISOLATES CAUSING LOWER RESPIRATORY TRACT INFECTIONS (LRTI) AMONG HIV/AIDS PATIENTS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY (HAART) IN UYO, SOUTH-SOUTH NIGERIA. BACKGROUND: Antibiotic-resistant genes (ARGs) pose a significant challenge in modern medicine, rendering infections increasingly difficult to treat as bacteria acquire mechanisms to resist antibiotics. Addressing ARGs necessitates a multifaceted approach, encompassing surveillance efforts to monitor their presence and the development of strategies aimed at managing and curbing the spread of antibiotic resistance. Hence, this study characterized the genetic determinants of antibiotic resistance among isolates responsible for Lower Respiratory Tract Infections (LRTIs) in People Living with HIV/AIDS (PLWHA) in Uyo. METHODS: Sputum samples were collected from 61 LRTI suspects, with bacterial isolates identified using VITEK-2 technology. Polymerase chain reaction assays were employed to detect resistance genes within the isolates. RESULTS: Results revealed a bacterial etiology in 39.3% of the samples, with a majority (79.2%) originating from St. Luke Hospital, Anua (SLHA), and the remainder (20.8%) from the University of Uyo Teaching Hospital (UUTH). Staphylococcus aureus emerged as the predominant isolate (46.6%), while resistance was notably high against Gentamicin and Sulphamethazole/Trimethoprim. Conversely, Azithromycin, imipenem, clindamycin, erythromycin, and ceftriaxone displayed relatively lower resistance levels across all isolates. Notably, four resistance genes CTX-M, Aac, KPC, and MecA were identified, with CTX-M detected in all multidrug-resistant isolates. This underscores the predominantly community-acquired nature of resistance as conferred by CTX-M. CONCLUSION: In conclusion, this study underscores the critical importance of continued vigilance and proactive measures in combating antibiotic resistance, particularly within vulnerable populations such as PLWHA. By elucidating the genetic mechanisms underlying antibiotic resistance, informed targeted interventions can be mitigated to curb threats posed by multidrug-resistant bacteria in clinical settings.202440385712
669130.9852The antimicrobial resistance monitoring and research (ARMoR) program: the US Department of Defense response to escalating antimicrobial resistance. Responding to escalating antimicrobial resistance (AMR), the US Department of Defense implemented an enterprise-wide collaboration, the Antimicrobial Resistance Monitoring and Research Program, to aid in infection prevention and control. It consists of a network of epidemiologists, bioinformaticists, microbiology researchers, policy makers, hospital-based infection preventionists, and healthcare providers who collaborate to collect relevant AMR data, conduct centralized molecular characterization, and use AMR characterization feedback to implement appropriate infection prevention and control measures and influence policy. A particularly concerning type of AMR, carbapenem-resistant Enterobacteriaceae, significantly declined after the program was launched. Similarly, there have been no further reports or outbreaks of another concerning type of AMR, colistin resistance in Acinetobacter, in the Department of Defense since the program was initiated. However, bacteria containing AMR-encoding genes are increasing. To update program stakeholders and other healthcare systems facing such challenges, we describe the processes and impact of the program.201424795331
669040.9852Antimicrobial resistance situation in animal health of Bangladesh. Antimicrobial resistance (AMR) is a crucial multifactorial and complex global problem and Bangladesh poses a regional and global threat with a high degree of antibiotic resistance. Although the routine application of antimicrobials in the livestock industry has largely contributed to the health and productivity, it correspondingly plays a significant role in the evolution of different pathogenic bacterial strains having multidrug resistance (MDR) properties. Bangladesh is implementing the National Action Plan (NAP) for containing AMR in human, animal, and environment sectors through "One Health" approach where the Department of Livestock Services (DLS) is the mandated body to implement NAP strategies in the animal health sector of the country. This review presents a "snapshot" of the predisposing factors, and current situations of AMR along with the weakness and strength of DLS to contain the problem in animal farming practices in Bangladesh. In the present review, resistance monitoring data and risk assessment identified several direct and/or indirect predisposing factors to be potentially associated with AMR development in the animal health sector of Bangladesh. The predisposing factors are inadequate veterinary healthcare, monitoring and regulatory services, intervention of excessive informal animal health service providers, and farmers' knowledge gap on drugs, and AMR which have resulted in the misuse and overuse of antibiotics, ultimate in the evolution of antibiotic-resistant bacteria and genes in all types of animal farming settings of Bangladesh. MDR bacteria with extreme resistance against antibiotics recommended to use in both animals and humans have been reported and been being a potential public health hazard in Bangladesh. Execution of extensive AMR surveillance in veterinary practices and awareness-building programs for stakeholders along with the strengthening of the capacity of DLS are recommended for effective containment of AMR emergence and dissemination in the animal health sector of Bangladesh.202033487990
665050.9851 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.200932644325
980860.9850Understanding Recent Developments in Colistin Resistance: Mechanisms, Clinical Implications, and Future Perspectives. Colistin resistance, driven by chromosomal mutations and the spread of plasmid-mediated MCR genes, has emerged as a critical challenge in combating multidrug-resistant Gram-negative bacteria. This resistance compromises the efficacy of colistin, leading to higher treatment failure rates, prolonged hospitalizations, and increased mortality. Recent studies have highlighted key mechanisms, including lipid A modifications, that enable bacteria to evade colistin's effects. The global spread of MCR genes exacerbates the issue, underlining the need for improved diagnostics and rapid detection of resistant strains to prevent adverse patient outcomes. To combat this growing threat, a multifaceted approach is essential, involving enhanced antimicrobial stewardship, stricter infection control measures, and continued research into alternative therapies and diagnostic methods. Collaborative efforts from researchers, healthcare providers, policymakers, and the pharmaceutical industry are crucial to preserving colistin's effectiveness and mitigating the broader impact on public health.202541148650
250070.9848The crisis of carbapenemase-mediated carbapenem resistance across the human-animal-environmental interface in India. Carbapenems are the decision-making antimicrobials used to combat severe Gram-negative bacterial infections in humans. Carbapenem resistance poses a potential public health emergency, especially in developing countries such as India, accounting for high morbidity, mortality, and healthcare cost. Emergence and transmission of plasmid-mediated "big five" carbapenemase genes including KPC, NDM, IMP, VIM and OXA-48-type among Gram-negative bacteria is spiralling the issue. Carbapenemase-producing carbapenem-resistant organisms (CP-CRO) cause multi- or pan-drug resistance by co-harboring several antibiotic resistance determinants. In addition of human origin, animals and even environmental sites are also the reservoir of CROs. Spillage in food-chains compromises food safety and security and increases the chance of cross-border transmission of these superbugs. Metallo-β-lactamases, mainly NDM-1 producing CROs, are commonly shared between human, animal and environmental interfaces worldwide, including in India. Antimicrobial resistance (AMR) surveillance using the One Health approach has been implemented in Europe, the United-Kingdom and the United-States to mitigate the crisis. This concept is still not implemented in most developing countries, including India, where the burden of antibiotic-resistant bacteria is high. Lack of AMR surveillance in animal and environmental sectors underestimates the cumulative burden of carbapenem resistance resulting in the silent spread of these superbugs. In-depth indiscriminate AMR surveillance focusing on carbapenem resistance is urgently required to develop and deploy effective national policies for preserving the efficacy of carbapenems as last-resort antibiotics in India. Tracking and mapping of international high-risk clones are pivotal for containing the global spread of CP-CRO.202336241158
816180.9848Integrative strategies against multidrug-resistant bacteria: Synthesizing novel antimicrobial frontiers for global health. Concerningly, multidrug-resistant bacteria have emerged as a prime worldwide trouble, obstructing the treatment of infectious diseases and causing doubts about the therapeutic accidentalness of presently existing drugs. Novel antimicrobial interventions deserve development as conventional antibiotics are incapable of keeping pace with bacteria evolution. Various promising approaches to combat MDR infections are discussed in this review. Antimicrobial peptides are examined for their broad-spectrum efficacy and reduced ability to develop resistance, while phage therapy may be used under extreme situations when antibiotics fail. In addition, the possibility of CRISPR-Cas systems for specifically targeting and eradicating resistance genes from bacterial populations will be explored. Nanotechnology has opened up the route to improve the delivery system of the drug itself, increasing the efficacy and specificity of antimicrobial action while protecting its host. Discovering potential antimicrobial agents is an exciting prospect through developments in synthetic biology and the rediscovery of natural product-based medicines. Moreover, host-directed therapies are now becoming popular as an adjunct to the main strategies of therapeutics without specifically targeting pathogens. Although these developments appear impressive, questions about production scaling, regulatory approvals, safety, and efficacy for clinical employment still loom large. Thus, tackling the MDR burden requires a multi-pronged plan, integrating newer treatment modalities with existing antibiotic regimens, enforcing robust stewardship initiatives, and effecting policy changes at the global level. The international health community can gird itself against the growing menace of antibiotic resistance if collaboration between interdisciplinary bodies and sustained research endeavours is encouraged. In this study, we evaluate the synergistic potential of combining various medicines in addition to summarizing recent advancements. To rethink antimicrobial stewardship in the future, we provide a multi-tiered paradigm that combines pathogen-focused and host-directed strategies.202540914328
485290.9848Recent 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.201121986462
2492100.9848Mobile Tigecycline Resistance: An Emerging Health Catastrophe Requiring Urgent One Health Global Intervention. Mobile tigecycline resistance (MTR) threatens the clinical efficacy of the salvage antibiotic, tigecycline (TIG) used in treating deadly infections in humans caused by superbugs (multidrug-, extensively drug-, and pandrug-resistant bacteria), including carbapenem- and colistin-resistant bacteria. Currently, non-mobile tet(X) and mobile plasmid-mediated transmissible tet(X) and resistance-nodulation-division (RND) efflux pump tmexCD-toprJ genes, conferring high-level TIG (HLT) resistance have been detected in humans, animals, and environmental ecosystems. Given the increasing rate of development and spread of plasmid-mediated resistance against the two last-resort antibiotics, colistin (COL) and TIG, there is a need to alert the global community on the emergence and spread of plasmid-mediated HLT resistance and the need for nations, especially developing countries, to increase their antimicrobial stewardship. Justifiably, MTR spread projects One Health ramifications and portends a monumental threat to global public and animal health, which could lead to outrageous health and economic impact due to limited options for therapy. To delve more into this very important subject matter, this current work will discuss why MTR is an emerging health catastrophe requiring urgent One Health global intervention, which has been constructed as follows: (a) antimicrobial activity of TIG; (b) mechanism of TIG resistance; (c) distribution, reservoirs, and traits of MTR gene-harboring isolates; (d) causes of MTR development; (e) possible MTR gene transfer mode and One Health implication; and (f) MTR spread and mitigating strategies.202235979498
2515110.9847High-risk Pseudomonas aeruginosa clones harboring β-lactamases: 2024 update. Carbapenem-resistant Pseudomonas aeruginosa is defined by the World Health Organization as a "high priority" in developing new antimicrobials. Indeed, the emergence and spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacteria increase the morbidity and mortality risk of infected patients. Genomic variants of P. aeruginosa that display phenotypes of MDR/XDR have been defined as high-risk global clones. In this mini-review, we describe some international high-risk clones that carry β-lactamase genes that can produce chronic colonization and increase infected patients' morbidity and mortality rates.202539850428
4887120.9847Mechanisms of Bacterial Drug Resistance with Special Emphasis on Phenotypic and Molecular Characterization of Extended Spectrum Beta-lactamase. Antibiotics are designed to effectively treat bacterial infections while minimizing harm to the human body. They work by targeting specific components of bacteria or by disrupting essential processes such as cell wall synthesis, membrane function, protein production, and metabolic pathways. However, the misuse and overuse of antibiotics have led to the emergence of drug resistance in humans, animals, and agriculture, contributing to the global spread of this problem. Drug resistance can be either innate or acquired, with acquired resistance involving changes in the bacterial chromosomes or transferable elements. Bacterial species employ various mechanisms of drug resistance, including modifying the antibiotic targets, inactivating the drug, reducing uptake or increasing efflux, overexpressing the target, utilizing alternative pathways, and forming biofilms. One significant concern in the realm of drug resistance revolves around the emergence and proliferation of extended-spectrum beta-lactamases (ESBLs), a gene that is found in most gram-negative bacteria, primarily carried by Escherichia coli and Klebsiella pneumoniae in healthcare settings. ESBL-mediated resistance poses challenges for diagnosis, treatment, infection control, and antibiotic stewardship. Accurate detection of ESBL genes is crucial, and phenotypic methods are commonly used for initial screening. However, these methods have limitations, and confirmatory molecular techniques such as PCR and DNA sequencing are employed to accurately identify ESBL genes. Despite the significant global concerns surrounding ESBLs, they have spread worldwide, mainly facilitated by healthcare settings, inappropriate antimicrobial use, and host susceptibility. Addressing this issue requires implementing comprehensive measures, including enhanced surveillance, strict infection control practices, antibiotic stewardship programs, rapid diagnostic methods, alternative therapies, public education initiatives, and research focused on developing new drugs. Furthermore, collaboration among the healthcare, public health, and research sectors is pivotal in effectively combating the escalating threat posed by ESBL-mediated resistance. Antibiotics have revolutionized medical care by effectively treating bacterial infections. However, the emergence of ESBL gene resistance poses a global challenge that requires an integrated approach to prevent a threatening future.202438700878
5012130.9847Extended-spectrum beta-lactamases-producing gram-negative bacteria in companion animals: action is clearly warranted! Extended-spectrum beta-lactamases (ESBL)-producing Gram-negative bacteria pose a serious threat to Public Health in human medicine as well as increasingly in the veterinary context worldwide. Several studies reported the transmission of zoonotic multidrug resistant bacteria between food-producing animals and humans, whilst the contribution of companion animals to this scenario is rather unknown. Within the last decades a change in the social role of companion animals has taken place, resulting in a very close contact between owners and their pets. As a consequence, humans may obtain antimicrobial resistant bacteria or the corresponding resistance genes not only from food-producing animals but also via close contact to their pets.This may give rise to bacterial infections with limited therapeutic options and an increased risk of treatment failure. As beta-lactams constitute one of the most important groups of antimicrobial agents in veterinary medicine, retaliatory actions in small animal and equine practices are urgently needed. This review addresses the increasing burden of extended-spectrum beta-lactam resistance among Enterobacteriaceae isolated from companion animals. It should emphasize the urgent need for the implementation of antibiotic stewardship as well as surveillance and monitoring programs of multi resistant bacteria in particular in view of new putative infection cycles between humans and their pets.201121462862
2505140.9847Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting.200616813979
2504150.9847Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum. Nonfermenting gram-negative bacteria pose a particular difficulty for the healthcare community because they represent the problem of multidrug resistance to the maximum. Important members of the group in the United States include Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Burkholderia cepacia. These organisms are niche pathogens that primarily cause opportunistic healthcare-associated infections in patients who are critically ill or immunocompromised. Multidrug resistance is common and increasing among gram-negative nonfermenters, and a number of strains have now been identified that exhibit resistance to essentially all commonly used antibiotics, including antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, trimethoprim-sulfamethoxazole, and carbapenems. Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P aeruginosa, Acinetobacter spp, and S maltophilia. However, most multidrug-resistant B cepacia are not susceptible to polymyxins, and systemic polymyxins carry the risk of nephrotoxicity for all patients treated with these agents, the elderly in particular. A variety of resistance mechanisms have been identified in P aeruginosa and other gram-negative nonfermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target-site alterations. Multiple resistance genes frequently coexist in the same organism. Multidrug resistance in gram-negative nonfermenters makes treatment of infections caused by these pathogens both difficult and expensive. Improved methods for susceptibility testing are needed when dealing with these organisms, including emerging strains expressing metallo-beta-lactamases. Improved antibiotic stewardship and infection-control measures will be needed to prevent or slow the emergence and spread of multidrug-resistant, nonfermenting gram-negative bacilli in the healthcare setting.200616735148
6617160.9846Mechanisms in colistin-resistant superbugs transmissible from veterinary, livestock and animal food products to humans. In the era of antibiotic resistance, where multidrug-resistant (MDR), extensively drug resistant (XDR), and pan-drug resistant (PDR) Gram-negative infections are prevalent, it is crucial to identify the primary sources of antibiotic resistance, understand resistant mechanisms, and develop strategies to combat these mechanisms. The emergence of resistance to last-resort antibiotics like colistin has sparked a war between humanity and resistant bacteria, leaving humanity struggling to find effective countermeasures. Although colistin is used as a highly toxic antibiotic in infections that are not treated with routine antibiotics, its widespread use in animal breeding and veterinary medicine has contributed to the spread of colistin-resistant bacteria, plasmid-borne colistin resistance genes (mcr), and antibiotic residues in livestock and animal-derived foods. These sources can potentially transmit colistin resistance to humans through various routes. Therefore, managing the use of colistin in livestock and animal foods, implementing strict monitoring, and establishing guidelines for its proper use are essential to prevent the escalation of colistin resistance. This review article discusses the latest mechanisms of colistin antibiotic resistance, particularly biofilm production as a public health threat, the livestock and animal food sources of this resistance, and the routes of transmission to humans.202540386099
6045170.9846Lacticaseicin 30 and Colistin as a Promising Antibiotic Formulation against Gram-Negative β-Lactamase-Producing Strains and Colistin-Resistant Strains. Antimicrobial resistance is a global health concern across the world and it is foreseen to swell if no actions are taken now. To help curbing this well announced crisis different strategies are announced, and these include the use of antimicrobial peptides (AMP), which are remarkable molecules known for their killing activities towards pathogenic bacteria. Bacteriocins are ribosomally synthesized AMP produced by almost all prokaryotic lineages. Bacteriocins, unlike antibiotics, offer a set of advantages in terms of cytotoxicity towards eukaryotic cells, their mode of action, cross-resistance and impact of microbiota content. Most known bacteriocins are produced by Gram-positive bacteria, and specifically by lactic acid bacteria (LAB). LAB-bacteriocins were steadily reported and characterized for their activity against genetically related Gram-positive bacteria, and seldom against Gram-negative bacteria. The aim of this study is to show that lacticaseicin 30, which is one of the bacteriocins produced by Lacticaseibacillus paracasei CNCM I-5369, is active against Gram-negative clinical strains (Salmonella enterica Enteritidis H10, S. enterica Typhimurium H97, Enterobacter cloacae H51, Escherichia coli H45, E. coli H51, E. coli H66, Klebsiella oxytoca H40, K. pneumoniae H71, K. variicola H77, K. pneumoniae H79, K. pneumoniae H79), whereas antibiotics failed. In addition, lacticaseicin 30 and colistin enabled synergistic interactions towards the aforementioned target Gram-negative clinical strains. Further, the combinations of lacticaseicin 30 and colistin prompted a drastic downregulation of mcr-1 and mcr-9 genes, which are associated with the colistin resistance phenotypes of these clinical strains. This report shows that lacticaseicin 30 is active against Gram-negative clinical strains carrying a rainbow of mcr genes, and the combination of these antimicrobials constitutes a promising therapeutic option that needs to be further exploited.202135052897
9790180.9846Emerging antibiotic resistance: carbapenemase-producing enterobacteria. Bad new bugs, still no new drugs. Antimicrobial resistance (AMR) is a global health security threat requiring actions across government sectors and society. Many factors are involved in this phenomenon, being overuse of antibiotics, incorrect antibiotic prophylaxis, and use of antibiotics for zootechnic reasons the main causes of the increasing rate of multi-drug resistant (MDR) bacteria. The impact of resistance to antimicrobials is an important threat due also to the emergence of MDR Gram-negative bacteria resistant to carbapenems, and the lack of the research for new active molecules. The production of extended spectrum beta-lactamase enzymes has been the first threatening mechanism for Gram-negative resistance to antibiotics, which prompted the development of new classes of antibiotics such as carbapenems. Unfortunately, resistance to carbapenems developed because of multiple mechanisms including efflux pumps, porin mutations and enzyme production, being the latter particularly relevant in terms of diffusion due to the genes located within plasmids that drive their horizontal diffusion. In this scenario, antimicrobial stewardship programs (ASP) are a mandatory resource in fighting the resistance spread. The reduction of total amount of antibiotics administration in the hospital setting and guiding prescribers in the correct administration of antibiotics for the smallest period possible, at the correct dosage, can be defined as the first goals of an ASP. Anyway, in an efficacious ASP, apart from antibiotic administration, efforts must been made in ensuring the lowest probability of spreading of MDR by efficacious measures of isolation of carriers, and by offering tools for a rapid diagnosis of viral infections avoiding the administration of unnecessary antibiotics. A continuous audit of the ASP programs and a correct assessment of the allergy to drugs such as penicillin have to complete the program. Currently, only a few options are available for patients with an infection sustained by Gram-negative MDR bacteria. All the options actually available are based on the administration of colystin, an old drug whose real efficacy is reduced due to its relevant toxicity, or on the administration of recently proposed drugs such as ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. All these new drugs do not have a novel mechanism of action and have limited spectrum in term of activity against MDR bacteria. In conclusion, antimicrobial resistance is a global emergence and AMP is the most powerful tool actually available. Few limited options are available to treat infections due to Carbapenem Resistant Enterobacteria. Antimicrobial molecules with true novel mechanism of action are needed to win the fight against antimicrobial resistance.201931846984
2495190.9846Transmission of Mobile Colistin Resistance (mcr-1) by Duodenoscope. BACKGROUND: Clinicians increasingly utilize polymyxins for treatment of serious infections caused by multidrug-resistant gram-negative bacteria. Emergence of plasmid-mediated, mobile colistin resistance genes creates potential for rapid spread of polymyxin resistance. We investigated the possible transmission of Klebsiella pneumoniae carrying mcr-1 via duodenoscope and report the first documented healthcare transmission of mcr-1-harboring bacteria in the United States. METHODS: A field investigation, including screening targeted high-risk groups, evaluation of the duodenoscope, and genome sequencing of isolated organisms, was conducted. The study site included a tertiary care academic health center in Boston, Massachusetts, and extended to community locations in New England. RESULTS: Two patients had highly related mcr-1-positive K. pneumoniae isolated from clinical cultures; a duodenoscope was the only identified epidemiological link. Screening tests for mcr-1 in 20 healthcare contacts and 2 household contacts were negative. Klebsiella pneumoniae and Escherichia coli were recovered from the duodenoscope; neither carried mcr-1. Evaluation of the duodenoscope identified intrusion of biomaterial under the sealed distal cap; devices were recalled to repair this defect. CONCLUSIONS: We identified transmission of mcr-1 in a United States acute care hospital that likely occurred via duodenoscope despite no identifiable breaches in reprocessing or infection control practices. Duodenoscope design flaws leading to transmission of multidrug-resistant organsisms persist despite recent initiatives to improve device safety. Reliable detection of colistin resistance is currently challenging for clinical laboratories, particularly given the absence of a US Food and Drug Administration-cleared test; improved clinical laboratory capacity for colistin susceptibility testing is needed to prevent the spread of mcr-carrying bacteria in healthcare settings.201930204838