Use Of Antimicrobials In Veterinary Medicine Research Articles

In Vitro Microevolution and Co-Selection Assessment of Florfenicol Impact on Escherichia coli Resistance Development.

The issue of antimicrobial resistance is becoming an increasingly serious challenge in both human and veterinary medicine. Prudent antimicrobial use in veterinary medicine is warranted and supported by international guidelines, with the Antimicrobial Advice Ad Hoc Expert Group (AMEG) placing particular emphasis on the critically important group B antimicrobials. These antimicrobials are commonly employed, especially in the poultry and swine industry. The impact of florfenicol, a veterinary antibiotic, was studied on the resistance development of Escherichia coli. The aim of the study was to investigate the effect of the use of florfenicol on the development of phenotypic and genomic resistances, not only to the drug itself but also to other drugs. The minimum inhibitory concentrations (MICs) of the antibiotics were investigated at 1×, 10×, 100× and 1000× concentrations using the adapted Microbial Evolution and Growth Arena (MEGA-plate) method. The results demonstrate that florfenicol can select for resistance to fluoroquinolone antibiotics (167× MIC value increase) and cephalosporins (67× MIC value increase). A total of 44 antimicrobial resistance genes were identified, the majority of which were consistent across the samples. Chromosomal point mutations, including alterations in resistance-associated and regulatory genes (acrB, acrR, emrR and robA), are thought to trigger multiple drug efflux pump activations, leading to phenotypically increased resistance. The study underscores the impact of florfenicol and its role in the development of antimicrobial resistance, particularly concerning fluoroquinolone antibiotics and cephalosporins. This study is the first to report florfenicol's dose-dependent enhancement of other antibiotics' MICs, linked to mutations in SOS-box genes (mdtABC-tolC, emrAB-tolC and acrAB-tolC) and increased multidrug efflux pump genes. Mutations in the regulatory genes acrR, emrR and rpbA support the possibility of increased gene expression. The results are crucial for understanding antimicrobial resistance and its development, highlighting the promising potential of in vitro evolutionary and coselection studies for future research.

The economics of antimicrobial resistance in veterinary medicine: Optimizing societal benefits through mesoeconomic approaches from public and private perspectives

Antimicrobial resistance (AMR) is a global public health threat driven by a combination of factors, including antimicrobial use (AMU) and interactions among microorganisms, people, animals and the environment. The emergence and spread of AMR in veterinary medicine (AMR-V) arising from AMU in veterinary medicine (AMU-V) can be linked to individuals' economic behaviour and institutional context. We highlight the limitations of current microeconomic approaches and propose a mesoeconomic conceptual model of AMR-V that integrates actors' strategic and routine behaviours in their context from a dynamic perspective using the concepts of externality, globality and futurity. The global solution to AMR-V management relies on a trade-off between i) the global externality assessment of AMU-V with respect to AMR-V (public perspective) and ii) farm- or value chain-level marginal abatement cost evaluation (private perspective). The improvements realized by the proposed mesoeconomic conceptual model include i) the simultaneous fight against the emergence and spread of AMR-V and ii) a local decrease in AMU-V without any loss of competitiveness for private actors due to the development of adequate production standards. A set of generic equations describing the stepwise change in the scale of analysis is finally proposed. This original contribution to the global challenge of AMR through a mesoeconomic approach bring substantial improvement for better AMU. This model can be considered a way to smoothly promote institutional change and a call for public policies that support public private partnership in the development of adequate incentives. The model requires further development prior to its application in a given value-chain or territory.

Urinary tract infection and subclinical bacteriuria in cats: A clinical update.

Practical relevance:Urinary tract infection (UTI) is an important cause of feline lower urinary tract disease (FLUTD), particularly in female cats older than 10 years of age. In addition to cats with typical clinical signs of FLUTD or upper UTI, many cats have subclinical bacteriuria, but the clinical relevance of this is currently uncertain. UTIs are one of the most important indications for antimicrobial use in veterinary medicine and contribute to the development of antimicrobial resistance. Adherence to treatment guidelines and confinement to a few first-line antimicrobial agents is imperative to avoid further deterioration of the antimicrobial resistance situation. The decision to treat with antimicrobials should be based on the presence of clinical signs, and/or concurrent diseases, and the results of urine culture and susceptibility testing.Clinical challenges:Distinguishing between cats with bacterial cystitis, and those with idiopathic cystitis and concurrent clinical or subclinical bacteriuria, is challenging, as clinical signs and urinalysis results may be identical. Optimal treatment of subclinical bacteriuria requires clarification as there is currently no evidence that demonstrates a beneficial effect of routine treatment. Management of recurrent UTIs remains a challenge as evidence for most alternatives used for prevention in cats is mainly anecdotal, and no preventive treatment modality is currently recommended.Evidence base:This review draws on an extensive literature base in veterinary and human medicine, including the recently updated guidelines of the International Society for Companion Animal Infectious Diseases for the diagnosis and management of bacterial urinary tract infections in dogs and cats. Where published evidence is lacking, the authors describe their own approach; notably, for the bacteriuric cat with chronic kidney disease.

Serotype Diversity and Antimicrobial Resistance among Salmonella enterica Isolates from Patients at an Equine Referral Hospital.

Although Salmonella enterica can produce life-threatening colitis in horses, certain serotypes are more commonly associated with clinical disease. Our aim was to evaluate the proportional morbidity attributed to different serotypes, as well as the phenotypic and genotypic antimicrobial resistance (AMR) of Salmonella isolates from patients at an equine referral hospital in the southern United States. A total of 255 Salmonella isolates was obtained from clinical samples of patients admitted to the hospital between 2007 and 2015. Phenotypic resistance to 14 antibiotics surveilled by the U.S. National Antimicrobial Resistance Monitoring System was determined using a commercially available panel. Whole-genome sequencing was used to identify serotypes and genotypic AMR. The most common serotypes were Salmonella enterica serotype Newport (18%), Salmonella enterica serotype Anatum (15.2%), and Salmonella enterica serotype Braenderup (11.8%). Most (n = 219) of the isolates were pansusceptible, while 25 were multidrug resistant (≥3 antimicrobial classes). Genes encoding beta-lactam resistance, such as blaCMY-2, blaSHV-12, blaCTX-M-27, and blaTEM-1B, were detected. The qnrB2 and aac(6')-Ib-cr genes were present in isolates with reduced susceptibility to ciprofloxacin. Genes encoding resistance to gentamicin (aph(3')-Ia, aac(6')-IIc), streptomycin (strA and strB), sulfonamides (sul1), trimethoprim (dfrA), phenicols (catA), tetracyclines [tet(A) and tet(E)], and macrolides [ere(A)] were also identified. The main predicted incompatibility plasmid type was I1 (10%). Core genome-based analyses revealed phylogenetic associations between isolates of common serotypes. The presence of AMR Salmonella in equine patients increases the risk of unsuccessful treatment and causes concern for potential zoonotic transmission to attending veterinary personnel, animal caretakers, and horse owners. Understanding the epidemiology of Salmonella in horses admitted to referral hospitals is important for the prevention, control, and treatment of salmonellosis.IMPORTANCE In horses, salmonellosis is a leading cause of life-threatening colitis. At veterinary teaching hospitals, nosocomial outbreaks can increase the risk of zoonotic transmission, lead to restrictions on admissions, impact hospital reputation, and interrupt educational activities. The antimicrobials most often used in horses are included in the 5th revision of the World Health Organization's list of critically important antimicrobials for human medicine. Recent studies have demonstrated a trend of increasing bacterial resistance to drugs commonly used to treat Salmonella infections. In this study, we identify temporal trends in the distribution of Salmonella serotypes and their mechanisms of antimicrobial resistance; furthermore, we are able to determine the likely origin of several temporal clusters of infection by using whole-genome sequencing. These data can be used to focus strategies to better contain the dissemination and enhance the mitigation of Salmonella infections and to provide evidence-based policies and guidelines to steward antimicrobial use in veterinary medicine.

Impact of Low and High Doses of Marbofloxacin on the Selection of Resistant Enterobacteriaceae in the Commensal Gut Flora of Young Cattle: Discussion of Data from 2 Study Populations.

In the context of requested decrease of antimicrobial use in veterinary medicine, our objective was to assess the impact of two doses of marbofloxacin administered on young bulls (YBs) and veal calves (VCs) treated for bovine respiratory disease, on the total population of Enterobacteriaceae in gut flora and on the emergence of resistant Enterobacteriaceae. In two independent experiments, 48 YBs from 6 commercial farms and 33 VCs previously colostrum deprived and exposed to cefquinome were randomly assigned to one of the three groups LOW, HIGH, and Control. In LOW and HIGH groups, animals received a single injection of, respectively, 2 and 10 mg/kg marbofloxacin. Feces were sampled before treatment, and at several times after treatment. Total and resistant Enterobacteriaceae enumerating were performed by plating dilutions of fecal samples on MacConkey agar plates that were supplemented or not with quinolone. In YBs, marbofloxacin treatment was associated with a transient decrease in total Enterobacteriaceae count between day (D)1 and D3 after treatment. Total Enterobacteriaceae count returned to baseline between D5 and D7 in all groups. None of the 48 YBs harbored marbofloxacin-resistant Enterobacteriaceae before treatment. After treatment, 1 out of 20 YBs from the Control group and 1 out of 14 YBs from the HIGH group exhibited marbofloxacin-resistant Enterobacteriaceae. In VCs, the rate of fluoroquinolone-resistant Enterobacteriaceae significantly increased after low and high doses of marbofloxacin treatment. However, the effect was similar for the two doses, which was probably related to the high level of resistant Enterobacteriaceae exhibited before treatment. Our results suggest that a single treatment with 2 or 10 mg/kg marbofloxacin exerts a moderate selective pressure on commensal Enterobacteriaceae in YBs and in VCs. A fivefold decrease of marbofloxacin regimen did not affect the selection of resistances among commensal bacteria.

Pharmacokinetic–pharmacodynamic (PK–PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs

One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic–pharmacodynamic (PK–PD) principles to dosing regimens. If antimicrobials are used appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK–PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK–PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration.

Influences on antimicrobial prescribing behaviour of veterinary practitioners in cattle practice in Ireland

Guidelines on prudent antimicrobial use in veterinary medicine have been developed to reduce inappropriate prescribing of antimicrobials. Such guidelines focus mainly on the clinical and pharmacological indications for prescribing. A...

Factors associated with methicillin-resistant versus methicillin-susceptible Staphylococcus pseudintermedius infection in dogs

To compare methicillin-resistant Staphylococcus pseudintermedius (MRSP) and methicillin-susceptible S pseudintermedius (MSSP) infections in dogs. Multicenter case-control study. Dogs with MRSP infections were matched, by hospital, with 2 MSSP controls, with the infections occurring immediately before and after the case infection. Signalment, historical, clinical, treatment, and outcome data were documented. Conditional logistic regression was performed. A manual stepwise backward elimination procedure was used to build the multivariable model. 56 case and 112 control dogs were enrolled. Pyoderma was the most common infection type in both groups. In the final multivariable model, systemic administration of antimicrobials within 30 days prior to infection was significantly associated with an MRSP versus an MSSP infection (OR, 9.9; 95% confidence interval, 3.59 to 27.53). The association of prior antimicrobial administration and MRSP infection indicated the potential impact of routine antimicrobial use in veterinary medicine on antimicrobial resistance and the need for prudent use of these important drugs. Mortality rate was not significantly different between MRSP and MSSP infections; the lack of a significant difference suggested that MRSP was inherently no more virulent than MSSP, provided the infection was properly diagnosed and appropriate treatment was started. Basic concepts such as prudent antimicrobial use and early diagnosis through timely submission of appropriate culture specimens therefore can be important measures to try to reduce the impact of this pathogen.

Résistance aux antibiotiques chez les bactéries d’origine animale

In the European Union, antimicrobials are administered to animals as veterinary drugs. Monitoring of antimicrobial resistance of zoonotic and indicator bacteria were implemented at the European level during the last decade. This methodology can be applied for emerging bacteria observed at a national level to provide data for a risk characterization towards a risk analysis. Tools for monitoring antimicrobial use in veterinary medicine are developed and need to be harmonized at the European level. Development of antimicrobial resistance for veterinary pathogens must be managed to maintain their efficacy in animal health. Engagement of veterinarians and professionals of animal production is on going to preserve efficacy of antimicrobials in human and animal medicine.

Antimicrobial resistance in equine faecal Escherichia coli isolates from North West England

BackgroundEscherichia coli isolates of equine faecal origin were investigated for antibiotic resistance, resistance genes and their ability to perform horizontal transfer.MethodsIn total, 264 faecal samples were collected from 138 horses in hospital and community livery premises in northwest England, yielding 296 resistant E. coli isolates. Isolates were tested for susceptibility to antimicrobial drugs by disc diffusion and agar dilution methods in order to determine minimum inhibitory concentrations (MIC). PCR amplification was used to detect genes conferring resistance to: ampicillin (TEM and SHV beta-lactamase), chloramphenicol (catI, catII, catIII and cml), tetracycline (tetA, tetB, tetC, tetD, tet E and tetG), and trimethoprim (dfrA1, dfrA9, dfrA12, dfrA13, dfr7, and dfr17).ResultsThe proportion of antibiotic resistant isolates, and multidrug resistant isolates (MDR) was significantly higher in hospital samples compared to livery samples (MDR: 48% of hospital isolates; 12% of livery isolates, p < 0.001). Resistance to ciprofloxacin and florfenicol were identified mostly within the MDR phenotypes. Resistance genes included dfr, TEM beta-lactamase, tet and cat, conferring resistance to trimethoprim, ampicillin, tetracycline and chloramphenicol, respectively. Within each antimicrobial resistance group, these genes occurred at frequencies of 93% (260/279), 91%, 86.8% and 73.5%, respectively; with 115/296 (38.8%) found to be MDR isolates. Conjugation experiments were performed on selected isolates and MDR phenotypes were readily transferred.ConclusionsOur findings demonstrate that E. coli of equine faecal origin are commonly resistant to antibiotics used in human and veterinary medicine. Furthermore, our results suggest that most antibiotic resistance observed in equine E. coli is encoded by well-known and well-characterized resistant genes common to E. coli from man and domestic animals. These data support the ongoing concern about antimicrobial resistance, MDR, antimicrobial use in veterinary medicine and the zoonotic risk that horses could potentially pose to public health.

Prevalence of antimicrobial resistance among bacterial pathogens isolated from cattle in different European countries: 2002–2004

BackgroundThe project "Antibiotic resistance in bacteria of animal origin – II" (ARBAO-II) was funded by the European Union (FAIR5-QLK2-2002-01146) for the period 2003–2005, with the aim to establish a continuous monitoring of antimicrobial susceptibility among veterinary laboratories in European countries based on validated and harmonised methodologies. Available summary data of the susceptibility testing of the bacterial pathogens from the different laboratories were collected.MethodAntimicrobial susceptibility data for several bovine pathogens were obtained over a three year period (2002–2004). Each year the participating laboratories were requested to fill in excel-file templates with national summary data on the occurrence of antimicrobial resistance from different bacterial species.A proficiency test (EQAS – external quality assurance system) for antimicrobial susceptibility testing was conducted each year to test the accuracy of antimicrobial susceptibility testing in the participating laboratories. The data from this testing demonstrated that for the species included in the EQAS the results are comparable between countries.ResultsData from 25,241 isolates were collected from 13 European countries. For Staphylococcus aureus from bovine mastitis major differences were apparent in the occurrence of resistance between countries and between the different antimicrobial agents tested. The highest frequency of resistance was observed for penicillin. For Mannheimia haemolytica resistance to ampicillin, tetracycline and trimethoprim/sulphonamide were observed in France, the Netherlands and Portugal. All isolates of Pasteurella multocida isolated in Finland and most of those from Denmark, England (and Wales), Italy and Sweden were susceptible to the majority of the antimicrobials. Streptococcus dysgalactiae and Streptococcus uberis isolates from Sweden were fully susceptible. For the other countries some resistance was observed to tetracycline, gentamicin and erythromycin. More resistance and variation of the resistance levels between countries were observed for Escherichia coli compared to the other bacterial species investigated.ConclusionIn general, isolates from Denmark, England (and Wales), the Netherlands, Norway, Sweden and Switzerland showed low frequencies of resistance, whereas many isolates from Belgium, France, Italy, Latvia and Spain were resistant to most antimicrobials tested. In the future, data on the prevalence of resistance should be used to develop guidelines for appropriate antimicrobial use in veterinary medicine.