scholarly journals Mechanisms of quinolone resistance and implications for human and animal health

2010 ◽  
Vol 64 (3-4) ◽  
pp. 277-285
Author(s):  
Maja Velhner ◽  
Gordana Kozoderovic ◽  
Zora Jelesic ◽  
Igor Stojanov ◽  
Radomir Ratajac ◽  
...  

Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC) to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance). The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .

2018 ◽  
Vol 20 (87) ◽  
pp. 19-26 ◽  
Author(s):  
T.I. Stetsko ◽  
V.P. Muzyka ◽  
V.M. Hunchak

The resistance of microorganisms, bacterial pathogens, to antimicrobials is a global problem in both healthcare and veterinary medicine. It is believed that the main reason for the emergence and spread of antimicrobial resistance in humans is the transfer of antibiotic resistant strains of microorganisms or genes, determinants of resistance, through products of animal origin from productive animals to humans. Thus, the main way of antimicrobial resistance containment is to restrain and minimize it through the prudent use of antibiotics in veterinary medicine, especially those that are critically important for productive animals. In addition, some classes of antibacterial substances and antibiotics, that are widely used in humane medicine, are used in veterinary medicine. The need to use and preserve these important therapeutic agents is relevant from the point of view of the concept «One Health». The article provides a list of all antibacterial substances used by productive animals for their importance in veterinary medicine, developed by a special group of experts of the World Organisation for Animal Health (OIE). Any antimicrobial agent authorized for use in veterinary medicine for productive animals, in accordance with the criteria for quality, safety and efficacy as defined in Section 6.9 of the Terrestrial Animal Health Code, is considered to be important for veterinary medicine. All the antimicrobial substances used for productive animals are divided in this list on critical, very important and important for veterinary medicine. Attention was also drawn to the peculiarities of the use of critical antimicrobial agents in veterinary medicine, especially those recognized as critical in humane medicine. These include aminoglycosides, cephalosporins of the 3rd and 4th generation, fluoroquinolones, glycopeptides, macrolides, some penicillins and polymyxins. The article also describes the classification of critical antimicrobials by the European Medicines Agency (EMA) and the Panel of Experts on Antimicrobials (AMEG) of the WHO based on the risk profile for humans through the development of antimicrobial resistance after application to productive animals. Such an assessment will give veterinary practitioners an important justification when they make decisions about the clinical treatment of bacterial infections and the responsible appointment of antimicrobial therapy. This will help to reach the balance among the achievement of the effectiveness of antimicrobial therapy of productive animals, reducing of the selective pressure on the development of antibiotic resistance and ensuring of a high level of human health.


Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 691
Author(s):  
Sarah Moser ◽  
Helena Seth-Smith ◽  
Adrian Egli ◽  
Sonja Kittl ◽  
Gudrun Overesch

Campylobacter (C.) spp. from poultry is the main source of foodborne human campylobacteriosis, but diseased pets and cattle shedding Campylobacter spp. may contribute sporadically as a source of human infection. As fluoroquinolones are one of the drugs of choice for the treatment of severe human campylobacteriosis, the resistance rates of C. jejuni and C. coli from poultry against antibiotics, including fluoroquinolones, are monitored within the European program on antimicrobial resistance (AMR) in livestock. However, much less is published on the AMR rates of C.jejuni and C. coli from pets and cattle. Therefore, C. jejuni and C. coli isolated from diseased animals were tested phenotypically for AMR, and associated AMR genes or mutations were identified by whole genome sequencing. High rates of resistance to (fluoro)quinolones (41%) and tetracyclines (61.1%) were found in C. jejuni (n = 29/66). (Fluoro)quinolone resistance was associated with the known point mutation in the quinolone resistance-determining region (QRDR) of gyrA, and tetracycline resistance was mostly caused by the tet(O) gene. These high rates of resistance, especially to critically important antibiotics in C. jejuni and C. coli, are worrisome not only in veterinary medicine. Efforts to preserve the efficacy of important antimicrobial treatment options in human and veterinary medicine have to be strengthened in the future.


mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Roderick M. Card ◽  
Shaun A. Cawthraw ◽  
Javier Nunez-Garcia ◽  
Richard J. Ellis ◽  
Gemma Kay ◽  
...  

ABSTRACT The chicken gastrointestinal tract is richly populated by commensal bacteria that fulfill various beneficial roles for the host, including helping to resist colonization by pathogens. It can also facilitate the conjugative transfer of multidrug resistance (MDR) plasmids between commensal and pathogenic bacteria which is a significant public and animal health concern as it may affect our ability to treat bacterial infections. We used an in vitro chemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase bla CTX-M1. We also evaluated the impact of cefotaxime administration on plasmid transfer and microbial diversity. Bacterial community profiles obtained by culture-independent methods showed that Salmonella inoculation resulted in no significant changes to bacterial community alpha diversity and beta diversity, whereas administration of cefotaxime caused significant alterations to both measures of diversity, which largely recovered. MDR plasmid transfer from Salmonella to commensal Escherichia coli was demonstrated by PCR and whole-genome sequencing of isolates purified from agar plates containing cefotaxime. Transfer occurred to seven E. coli sequence types at high rates, even in the absence of cefotaxime, with resistant strains isolated within 3 days. Our chemostat system provides a good representation of bacterial interactions, including antibiotic resistance transfer in vivo. It can be used as an ethical and relatively inexpensive approach to model dissemination of antibiotic resistance within the gut of any animal or human and refine interventions that mitigate its spread before employing in vivo studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies. IMPORTANCE The spread of antimicrobial resistance presents a grave threat to public health and animal health and is affecting our ability to respond to bacterial infections. Transfer of antimicrobial resistance via plasmid exchange is of particular concern as it enables unrelated bacteria to acquire resistance. The gastrointestinal tract is replete with bacteria and provides an environment for plasmid transfer between commensals and pathogens. Here we use the chicken gut microbiota as an exemplar to model the effects of bacterial infection, antibiotic administration, and plasmid transfer. We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies.


2021 ◽  
Vol 26 (4) ◽  
Author(s):  
Rodolphe Mader ◽  
Peter Damborg ◽  
Jean-Philippe Amat ◽  
Björn Bengtsson ◽  
Clémence Bourély ◽  
...  

Antimicrobial resistance (AMR) should be tackled through a One Health approach, as stated in the World Health Organization Global Action Plan on AMR. We describe the landscape of AMR surveillance in the European Union/European Economic Area (EU/EEA) and underline a gap regarding veterinary medicine. Current AMR surveillance efforts are of limited help to veterinary practitioners and policymakers seeking to improve antimicrobial stewardship in animal health. We propose to establish the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) to report on the AMR situation, follow AMR trends and detect emerging AMR in selected bacterial pathogens of animals. This information could be useful to advise policymakers, explore efficacy of interventions, support antimicrobial stewardship initiatives, (re-)evaluate marketing authorisations of antimicrobials, generate epidemiological cut-off values, assess risk of zoonotic AMR transmission and evaluate the burden of AMR in animal health. EARS-Vet could be integrated with other AMR monitoring systems in the animal and medical sectors to ensure a One Health approach. Herein, we present a strategy to establish EARS-Vet as a network of national surveillance systems and highlight challenges of data harmonisation and bias. Strong political commitment at national and EU/EEA levels is required for the success of EARS-Vet.


2020 ◽  
Vol 21 (6) ◽  
pp. 1914 ◽  
Author(s):  
Ernesto Palma ◽  
Bruno Tilocca ◽  
Paola Roncada

Antimicrobial resistance (AMR) represents one of the most important human- and animal health-threatening issues worldwide. Bacterial capability to face antimicrobial compounds is an ancient feature, enabling bacterial survival over time and the dynamic surrounding. Moreover, bacteria make use of their evolutionary machinery to adapt to the selective pressure exerted by antibiotic treatments, resulting in reduced efficacy of the therapeutic intervention against human and animal infections. The mechanisms responsible for both innate and acquired AMR are thoroughly investigated. Commonly, AMR traits are included in mobilizable genetic elements enabling the homogeneous diffusion of the AMR traits pool between the ecosystems of diverse sectors, such as human medicine, veterinary medicine, and the environment. Thus, a coordinated multisectoral approach, such as One-Health, provides a detailed comprehensive picture of the AMR onset and diffusion. Following a general revision of the molecular mechanisms responsible for both innate and acquired AMR, the present manuscript focuses on reviewing the contribution of veterinary medicine to the overall issue of AMR. The main sources of AMR amenable to veterinary medicine are described, driving the attention towards the indissoluble cross-talk existing between the diverse ecosystems and sectors and their cumulative cooperation to this warning phenomenon.


2009 ◽  
Vol 22 (4) ◽  
pp. 664-689 ◽  
Author(s):  
Jacob Strahilevitz ◽  
George A. Jacoby ◽  
David C. Hooper ◽  
Ari Robicsek

SUMMARY Although plasmid-mediated quinolone resistance (PMQR) was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. The best-described form of PMQR is determined by the qnr group of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described. aac(6′)-Ib-cr encodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent. oqxAB and qepA encode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 979
Author(s):  
Juan Carlos Hernández-González ◽  
Abigail Martínez-Tapia ◽  
Gebim Lazcano-Hernández ◽  
Blanca Estela García-Pérez ◽  
Nayeli Shantal Castrejón-Jiménez

In the search for an alternative treatment to reduce antimicrobial resistance, bacteriocins shine a light on reducing this problem in public and animal health. Bacteriocins are peptides synthesized by bacteria that can inhibit the growth of other bacteria and fungi, parasites, and viruses. Lactic acid bacteria (LAB) are a group of bacteria that produce bacteriocins; their mechanism of action can replace antibiotics and prevent bacterial resistance. In veterinary medicine, LAB and bacteriocins have been used as antimicrobials and probiotics. However, another critical role of bacteriocins is their immunomodulatory effect. This review shows the advances in applying bacteriocins in animal production and veterinary medicine, highlighting their biological roles.


2016 ◽  
Vol 82 (24) ◽  
pp. 7197-7204 ◽  
Author(s):  
Getahun E. Agga ◽  
John W. Schmidt ◽  
Terrance M. Arthur

ABSTRACTConcerns have been raised that in-feed chlortetracycline (CTC) may increase antimicrobial resistance (AMR), specifically tetracycline-resistant (TETr)Escherichia coliand third-generation cephalosporin-resistant (3GCr)E. coli. We evaluated the impact of a 5-day in-feed CTC prophylaxis on animal health, TETrE. coli, and 3GCrE. coli. A control group of cattle (n= 150) received no CTC, while a CTC group (n= 150) received in-feed CTC (10 mg/lb of body weight/day) from the 5th to the 9th day after feedlot arrival. Over 25% (38/150) of the animals in the control group developed illnesses requiring therapeutic treatment with antimicrobials critically important to human medicine. Only two animals (1.3%) in the CTC group required such treatments. Fecal swab and pen surface occurrences of genericE. coli(isolated on media that did not contain antimicrobials of interest and were not isolated based on any specific resistance), TETrE. coli, and 3GCrE. coliwere determined on five sampling occasions: arrival at the feedlot, 5 days posttreatment (5 dpt), 27 dpt, 75 dpt, and 117 dpt. On 5 dpt, TETrE. coliconcentrations were higher for the CTC group than the control group (P< 0.01). On 27 dpt, 75 dpt, and 117 dpt, TETrE. coliconcentrations did not differ between groups. 3GCrE. colioccurrences did not differ between control and CTC groups on any sampling occasion. For both groups, generic, TETr, and 3GCrE. colioccurrences were highest on 75 dpt and 117 dpt, suggesting that factors other than in-feed CTC contributed more significantly to antimicrobial-resistantE. colioccurrence.IMPORTANCEThe occurrence of human bacterial infections resistant to antimicrobial therapy has been increasing. It has been postulated that antimicrobial resistance was inevitable, but the life span of the antimicrobial era has been prematurely compromised due to the misuse of antimicrobials in clinical and agricultural practices. Direct evidence relating the use of antimicrobials in livestock production to diminished human health outcomes due to antimicrobial resistance is lacking, and the U.S. Food and Drug Administration has taken an approach to maximize therapeutic efficacy and minimize the selection of resistant microorganisms through judicious use of antimicrobials. This study demonstrated that prophylactic in-feed treatment of chlortetracycline administered for 5 days to calves entering feedlots is judicious, as this therapy reduced animal morbidity, reduced the use of antimicrobials more critical to human health, and had no long-term impact on the occurrence of antimicrobial-resistantE. coli.


Author(s):  
Tingrui Zhang ◽  
Linli Tao ◽  
Sukolrat Boonyayatra ◽  
Guoyi Niu

Bovine mastitis is one of the common diseases resulting in high economic losses in the dairy industry. Streptococcus uberis, the environmental or contagious pathogen, is one of the most frequently identified bacteria causing clinical and subclinical mastitis. Antimicrobials are commonly used to control bacterial infections in dairy cattle. The emergence of antimicrobial resistance (AMR) bacteria made the treatment of this disease by antimicrobials a challenge. Currently, AMR is a global threat to both human and animal health. This review summarizes the AMR profiles of S. uberis collected worldwide between the years 2000-2020. Most of the studies included in this review were from Europe, Estonia, Canada, Danish, Switzerland and Czech. In general, S. uberis is highly susceptible to β-lactam antimicrobials, whereas resistance to tetracyclines, macrolides, aminoglycosides antimicrobials occurred in most countries. The isolates against most antimicrobials presented an increasing pattern over time. It highlights that monitoring the AMR of S. uberis is crucial to reduce the public health crisis.


2021 ◽  
Author(s):  
Rodolphe Mader ◽  
Clémence Bourély ◽  
Jean-Philippe Amat ◽  
Els M. Broens ◽  
Luca Busani ◽  
...  

AbstractBackgroundBuilding the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach.ObjectivesThe objectives were to (i) define the combinations of animal species, production types, age categories, bacterial species, specimens and antimicrobials to be monitored in EARS-Vet and to (ii) determine antimicrobial test panels able to cover most combinations.MethodsThe EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the European Centre for Disease Prevention and Control (ECDC) and the European Food Safety Authority (EFSA).ResultsEARS-Vet would monitor AMR in six animal species (cattle, swine, chicken (broiler and laying hen), turkey, cat and dog), for 11 bacterial species (Escherichia coli, Klebsiella pneumoniae, Mannheimia haemolytica, Pasteurella multocida, Actinobacillus pleuropneumoniae, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus hyicus, Streptococcus uberis, Streptococcus dysgalactiae and Streptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Three test panels of antimicrobials were proposed covering most EARS-Vet combinations of relevance for veterinary antimicrobial stewardship.ConclusionsWith this scope, EARS-Vet would enable to better address animal health in the strategy to mitigate AMR and better understand the multi-sectoral AMR epidemiology in Europe.


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