Antibiotic Use in Veterinary

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotics Use and Antimicrobial Stewardship".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 20019

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Guest Editor
Veterinary Pharmacology & Toxicology Department, Universidad Complutense de Madrid, 28040 Madrid, Spain
Interests: antimicrobial resistance; pharmacokinetics; PK/PD modelling; dosage optimization
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Special Issue Information

Dear Colleagues,

The sustainable use of antibiotics in veterinary medicine is one of the greatest challenges for the scientific community, and is directly linked with the One Health concept. The use of antimicrobials in livestock is essential for animal welfare reasons and to achieve the productivity levels required to attend to the increasing demand for animal goods. However, the unwise use of antimicrobials has caused serious resistance problems in animals through the selection and amplification of resistance genes, as well as the presence of residues in food and the environment. The transmission of antimicrobial resistance genes between animals, humans, and the environment represents a public health concern requiring interdisciplinary approaches. Addressing this concern requires improvements in livestock production systems, i.e., better prevention of bacterial diseases and alternative infection control strategies, as well as scientific developments to improve our mechanistic understanding of the interaction of antimicrobials with bacterial microbiomes, i.e., through the application of "omic” technologies. While the use of antibiotics in livestock may be essential, it should account for the large interspecies pharmaco-/toxico-kinetic variability. Consequently, enhancing our knowledge on the pharmacokinetics and pharmacodynamics of antimicrobials in animal species is crucial. This Special Issue seeks to receive manuscripts that expand our understanding of antimicrobial resistance, as well as those that develop pharmacokinetic/pharmacodynamic models for optimising dosage regimens and minimizing antimicrobial resistance.

Submissions related to the following topics are particularly valued:

  • Antimicrobial resistance: resistance mechanisms, metagenomics, metabolomics, and epidemiology.
  • Pharmacokinetics and pharmacometrics: PK/PD population level approaches, pharmacokinetics, and metabolomics applied to pharmacokinetics.
  • Ecotoxicology.
  • Pharmacokinetic/pharmacodynamic modelling: pharmacodynamic modelling and dosage optimization.

Dr. Manuel San Andres
Guest Editor

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Keywords

  • pharmacokinetics
  • PK/PD modelling
  • pharmacodynamic modelling
  • antimicrobial resistance
  • metagenomics
  • metabolomics
  • resistome
  • pharmacometrics
  • antimicrobial residues

Published Papers (9 papers)

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Editorial

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3 pages, 195 KiB  
Editorial
Antibiotic Use in Veterinary
by Manuel San Andres
Antibiotics 2022, 11(11), 1539; https://doi.org/10.3390/antibiotics11111539 - 03 Nov 2022
Viewed by 1027
Abstract
Since the introduction of antibiotics in the 1930s, the form and philosophy of their use has changed considerably [...] Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)

Research

Jump to: Editorial

14 pages, 495 KiB  
Article
Attitude, Opinions, and Working Preferences Survey among Pet Practitioners Relating to Antimicrobials in India
by Kushal Grakh, Dinesh Mittal, Tarun Kumar, Swati Thakur, Diksha Panwar, Lokender Singh, Manesh Kumar and Naresh Jindal
Antibiotics 2022, 11(10), 1289; https://doi.org/10.3390/antibiotics11101289 - 22 Sep 2022
Cited by 2 | Viewed by 1857
Abstract
The indiscriminate usage and overuse of antimicrobials in pets or companion animals are underlying causes of antimicrobial resistance (AMR). Despite the multi-faceted global challenge presented by antimicrobial resistance, very few studies have appraised pet practitioners’ factors, such as written policy on antimicrobials, dose [...] Read more.
The indiscriminate usage and overuse of antimicrobials in pets or companion animals are underlying causes of antimicrobial resistance (AMR). Despite the multi-faceted global challenge presented by antimicrobial resistance, very few studies have appraised pet practitioners’ factors, such as written policy on antimicrobials, dose rate prescribed, use of critically important antimicrobials, and antimicrobial prescription in clean surgical procedures, which can contribute to AMR. In the present study, an online cross-sectional survey among randomly selected pet practitioners (n = 104) of various Indian provinces and union territories was conducted using a questionnaire comprising 33 closed-ended questions on different parameters, viz., the dosage regimen and level of compliance towards guidelines of the World Health Organization (WHO), other relevant veterinary associations, and their opinion while prescribing antimicrobials. Almost every practitioner of the 104 respondents had revealed the difficulties with owner compliance; i.e., incomplete course of the antibiotics, inappropriate follow-ups, and improper care of the sick animals. The majority of practitioners (95%) reported self-prescription of antimicrobials by the owner before presenting the pet(s) to the veterinary clinic, whereas more than half of the respondents (64%) revealed unavailability of antibiogram facilities. Furthermore, a large number (76%) of practitioners stated empirical treatment based on their experience as the main criteria for antimicrobial choice in the absence of timely results from the laboratory. Although non-necessitated use of antimicrobials in clean surgical procedures has been claimed, surprisingly, the majority of pet practitioners (97%) reported their use to reduce the post-operative complications. The use of the highest priority, critically important antimicrobials (HPCIA) listed by the WHO for humans, particularly quinolones and third-generation cephalosporin, also has been reported for different infections. The treatment durations were nearly as per the recommended guidelines issued by the Danish Small Animal Veterinary Association (DSAVA) for different ailments. Analysis using chi-square tests exhibited a significant correlation between less experienced veterinarians (less than 5 years) and prescription of antimicrobials restricted for critically important infections in human medicine. However, there seems to be no association between the experience of the practitioner and the further studied parameters, namely, antimicrobial regimen prescription, weighing the animals before prescription, dose rate calculation, and antimicrobial selection and use after clean surgical operations. The findings suggest periodic awareness campaigns among practitioners regarding the implementation of the official guidelines, the need for systematic surveillance of AMR, awareness among pet owners about antimicrobial resistance, and the importance of rational use of antimicrobials on their pets. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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13 pages, 1206 KiB  
Article
A Survey on the Rationale Usage of Antimicrobial Agents in Small Animal Clinics and Farms in Trinidad and Jamaica
by Muhammad Sani Ismaila, Alexandra Thomas-Rhoden, Angel Neptune, Kezia Sookram, Samantha Gopaul, Travis Padarath, Anil Persad, Karla Georges and Venkatesan Sundaram
Antibiotics 2022, 11(7), 885; https://doi.org/10.3390/antibiotics11070885 - 01 Jul 2022
Cited by 4 | Viewed by 1765
Abstract
The extensive and indiscriminate use of antibiotics is known to contribute to antimicrobial resistance. Unfortunately, there are no public records of antimicrobial use (frequency or dosage) administered to animals in two major CARICOM (Caribbean Community) countries: Trinidad and Tobago, and Jamaica. Surveillance would [...] Read more.
The extensive and indiscriminate use of antibiotics is known to contribute to antimicrobial resistance. Unfortunately, there are no public records of antimicrobial use (frequency or dosage) administered to animals in two major CARICOM (Caribbean Community) countries: Trinidad and Tobago, and Jamaica. Surveillance would promote amendments and discussion on a Caribbean antimicrobial-use protocol. In this study, an online survey was conducted using cross-sectional qualitative interviews via email, targeting veterinary clinicians working in clinics and farms in Trinidad and Jamaica, to identify how antimicrobials are used in the two countries. Out of the thirty-two (32) clinicians interviewed in Trinidad, 22 (68.75%) were small animal practitioners, and 10 (45.45%) were mixed practitioners. While in Jamaica, a total of Twenty six (26) clinicians responded, of which 17 of them (65.38%) were small animal practitioners and nine (34.62%) were mixed practitioners. A total of 95.2% of clinics and farms in Jamaica and 87.1% in Trinidad did not use standard antimicrobial protocols, which could be due to the limited availability of resources. The broad-spectrum antibiotic, amoxicillin, and amoxicillin/clavulanic acid were the most commonly used drugs in small animal practices in both countries (71.9% and 53.8% in dogs), (78.1% and 65.9% in cats); amoxicillin is also used frequently in mixed animal practice in Jamaica (44.4% in goats, 33.3% in cattle and 22.2% in sheep and pigs), while procaine penicillin and streptomycin was the most frequently used in mixed practice in Trinidad (60% in cattle and goats, 50% in sheep), which could explain the potentially increased risk of antimicrobial resistance. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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11 pages, 1182 KiB  
Article
The Urinary Resistome of Clinically Healthy Companion Dogs: Potential One Health Implications
by Tonatiuh Melgarejo, Nathan Sharp, Janina A. Krumbeck, Guangxi Wu, Young J. Kim and Annika Linde
Antibiotics 2022, 11(6), 780; https://doi.org/10.3390/antibiotics11060780 - 08 Jun 2022
Cited by 2 | Viewed by 2589
Abstract
An interdisciplinary approach to antimicrobial resistance (AMR) is essential to effectively address what is projected to soon become a public health disaster. Veterinary medicine accounts for a majority of antimicrobial use, and mainly in support of industrial food animal production (IFAP), which has [...] Read more.
An interdisciplinary approach to antimicrobial resistance (AMR) is essential to effectively address what is projected to soon become a public health disaster. Veterinary medicine accounts for a majority of antimicrobial use, and mainly in support of industrial food animal production (IFAP), which has significant exposure implications for human and nonhuman animals. Companion dogs live in close proximity to humans and share environmental exposures, including food sources. This study aimed to elucidate the AMR-gene presence in microorganisms recovered from urine from clinically healthy dogs to highlight public health considerations in the context of a species-spanning framework. Urine was collected through cystocentesis from 50 companion dogs in Southern California, and microbial DNA was analyzed using next-generation sequencing. Thirteen AMR genes in urine from 48% of the dogs {n=24} were detected. The most common AMR genes were aph(3′)Ia, and ermB, which confer resistance to aminoglycosides and MLS (macrolides, lincosamides, streptogramins) antibiotics, respectively. Antibiotic-resistance profiles based on the AMR genes detected, and the intrinsic resistance profiles of bacterial species, were inferred in 24% of the samples {n=12} for 57 species, with most belonging to Streptococcus, Staphylococcus, and Corynebacterium genera. The presence of AMR genes that confer resistance to medically important antibiotics suggests that dogs may serve as reservoirs of clinically relevant resistomes, which is likely rooted in excessive IFAP antimicrobial use. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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18 pages, 1784 KiB  
Article
Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against Staphylococcus aureus Isolated from Caprine Clinical Mastitis
by Augusto Matías Lorenzutti, Manuel Ignacio San Andrés-Larrea, Emilio Fernández-Varón, María del Pilar Zarazaga, Ana María Molina-López and Juan Manuel Serrano-Rodríguez
Antibiotics 2021, 10(11), 1290; https://doi.org/10.3390/antibiotics10111290 - 22 Oct 2021
Cited by 3 | Viewed by 1974
Abstract
Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction [...] Read more.
Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on S. aureus isolated from mastitis goats’ milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller–Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 105 and 108 CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC50 values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC24/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60–180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating S. aureus in lactating goats. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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17 pages, 1278 KiB  
Article
Pharmacokinetic Behavior and Pharmacokinetic/Pharmacodynamic Integration of Danofloxacin Following Single or Co-Administration with Meloxicam in Healthy Lambs and Lambs with Respiratory Infections
by Mehmet Nihat Ural and Kamil Uney
Antibiotics 2021, 10(10), 1190; https://doi.org/10.3390/antibiotics10101190 - 30 Sep 2021
Cited by 3 | Viewed by 2393
Abstract
The aim of this study was to determine the pharmacokinetics and pharmacodynamics of danofloxacin (DAN; 6 mg/kg) following subcutaneous administration alone or co-administration with meloxicam (MLX; 1 mg/kg) in healthy lambs and lambs with respiratory infections. The study was carried out using a [...] Read more.
The aim of this study was to determine the pharmacokinetics and pharmacodynamics of danofloxacin (DAN; 6 mg/kg) following subcutaneous administration alone or co-administration with meloxicam (MLX; 1 mg/kg) in healthy lambs and lambs with respiratory infections. The study was carried out using a total of four groups: HD (healthy; n = 6) and ID (infected; n = 7) groups who were administered DAN only, and HDM (healthy; n = 6) and IDM (infected; n = 7) groups who were administered DAN and MLX simultaneously. The plasma concentrations of DAN were determined using high-performance liquid chromatography–UV and analyzed by the non-compartmental method. DAN exhibited a similar elimination half-life in all groups, including both the healthy and infected lambs. The total clearance in the HDM, ID and IDM groups and volume of distribution in the HDM and IDM groups were significantly reduced. MLX in the IDM group significantly increased the area under the curve (AUC) and peak concentration (Cmax) of DAN compared to the HD group. The Mannheimia haemolytica, Escherichia coli, and Streptococcus spp. strains were isolated from bronchoalveolar lavage fluid samples of the infected lambs. When co-administration with meloxicam, DAN at a 6 mg/kg dose can provide optimum values of ƒAUC0–24/MIC (>56 h) and ƒCmax/MIC (>8) for susceptible M. haemolytica isolates with an MIC90 value of 0.25 µg/mL and susceptible E. coli isolates with an MIC value of ≤0.125 µg/mL. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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12 pages, 295 KiB  
Article
Supplementation of Live Yeast, Mannan Oligosaccharide, and Organic Selenium during the Adaptation Phase of Newly Arrived Beef Cattle: Effects on Health Status, Immune Functionality, and Growth Performance
by Silvia Grossi, Matteo Dell’Anno, Luciana Rossi, Riccardo Compiani and Carlo Angelo Sgoifo Rossi
Antibiotics 2021, 10(9), 1114; https://doi.org/10.3390/antibiotics10091114 - 15 Sep 2021
Cited by 15 | Viewed by 2081
Abstract
The effect of a nutraceutical mixture, based on live yeast (LY), mannan oligosaccharides (MOS) and organic selenium (Se) on health status, as well as immune functionality and growth performance in the fattening of newly received beef cattle, was evaluated. A total of 1036 [...] Read more.
The effect of a nutraceutical mixture, based on live yeast (LY), mannan oligosaccharides (MOS) and organic selenium (Se) on health status, as well as immune functionality and growth performance in the fattening of newly received beef cattle, was evaluated. A total of 1036 Charolaise heifers were allocated into two experimental groups: (i) control group, without any nutraceutical support (n = 487; initial weight = 325 ± 21 kg); and (ii) treatment group, supplementation during the first 30 days, with LY (5 g/head/day), organic Se (3 mg/head/day), and MOS (10 g/head/day) (n = 549; initial weight = 323 ± 23 kg). The incidence of bovine respiratory disease (BRD) and other health issues was monitored, as well as the mortality rate. Blood samples were taken at d0 and d30 to evaluate the immune functionality and the inflammatory status. Growth performances, feces chemical composition, and carcass characteristics were recorded. The BRD occurrence tended to be reduced (p = 0.06) in the Treatment group. The BHV-1 antibody production after vaccination was significantly improved (p = 0.031), as well as the bactericidal activity (p = 0.0012) in the Treatment group. No differences were found in the inflammatory status parameters. The final weight (p = 0.006) and the average daily gain at d30 (p < 0.0001) were significantly improved by the treatment. No differences were found in terms of carcass characteristics, while the fecal content of NDF (p < 0.0001), ADF (p = 0.0003), and starch (p < 0.0001) were significantly reduced by the treatment. The result of the present study suggests that the nutraceutical mixture used can support the animal’s immune systems, improving its ability to react against pathogens, as well as feed efficiency and growth performances during the whole fattening period. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
7 pages, 413 KiB  
Article
Pharmacokinetic Behaviour of Enrofloxacin after Single Intramuscular Dosage in American Black Vultures (Coragyps atratus)
by Samanta Waxman, José Julio de Lucas, Guillermo Wiemeyer, Laura Torres Bianchini, Manuel Ignacio San Andrés and Casilda Rodríguez
Antibiotics 2021, 10(8), 957; https://doi.org/10.3390/antibiotics10080957 - 09 Aug 2021
Cited by 3 | Viewed by 1761
Abstract
The aim of the study was to investigate the intramuscular pharmacokinetics of enrofloxacin in black vultures (Coragyps atratus). The pharmacokinetics of a single intramuscular dose (10 mg/kg) of enrofloxacin was studied in six vultures. Plasma concentrations of enrofloxacin and its active [...] Read more.
The aim of the study was to investigate the intramuscular pharmacokinetics of enrofloxacin in black vultures (Coragyps atratus). The pharmacokinetics of a single intramuscular dose (10 mg/kg) of enrofloxacin was studied in six vultures. Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined by high-performance liquid chromatography (HPLCuv). Pharmacokinetic parameters were estimated using non-compartmental and compartmental analysis. After intramuscular administration, enrofloxacin showed a rapid and complete absorption, reaching a Cmax value of 3.26 ± 0.23 μg/mL at 1.75 ± 0.53 h. A long terminal half-life of 19.58 h has been observed. Using previously published MIC values to perform a PK/PD analysis, cumulative fraction responses obtained after Monte Carlo simulation for AUC/MIC > 30, 50 and 125 were 72.93%, 72.34% and 30.86% for E. coli and 89.29%, 88.89% and 58.57% for Mycoplasma synoviae, respectively. Cumulative fraction responses obtained for Cmax/MIC index were 33.93% and 40.18% for E. coli and M. synoviae, respectively. The intramuscular administration of 10 mg/kg could be appropriate to treat infectious diseases caused by gram-positive bacteria with MIC value lower than 1 µg/mL; however, although enrofloxacin showed a slow elimination in black vultures, plasma concentrations were insufficient to reach the gram-negative stablished breakpoints. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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20 pages, 2540 KiB  
Article
Impact of Chronic Tetracycline Exposure on Human Intestinal Microbiota in a Continuous Flow Bioreactor Model
by Youngbeom Ahn, Ji Young Jung, Ohgew Kweon, Brian T. Veach, Sangeeta Khare, Kuppan Gokulan, Silvia A. Piñeiro and Carl E. Cerniglia
Antibiotics 2021, 10(8), 886; https://doi.org/10.3390/antibiotics10080886 - 21 Jul 2021
Cited by 11 | Viewed by 2976
Abstract
Studying potential dietary exposure to antimicrobial drug residues via meat and dairy products is essential to ensure human health and consumer safety. When studying how antimicrobial residues in food impact the development of antimicrobial drug resistance and disrupt normal bacteria community structure in [...] Read more.
Studying potential dietary exposure to antimicrobial drug residues via meat and dairy products is essential to ensure human health and consumer safety. When studying how antimicrobial residues in food impact the development of antimicrobial drug resistance and disrupt normal bacteria community structure in the intestine, there are diverse methodological challenges to overcome. In this study, traditional cultures and molecular analysis techniques were used to determine the effects of tetracycline at chronic subinhibitory exposure levels on human intestinal microbiota using an in vitro continuous flow bioreactor. Six bioreactor culture vessels containing human fecal suspensions were maintained at 37 °C for 7 days. After a steady state was achieved, the suspensions were dosed with 0, 0.015, 0.15, 1.5, 15, or 150 µg/mL tetracycline, respectively. Exposure to 150 µg/mL tetracycline resulted in a decrease of total anaerobic bacteria from 1.9 × 107 ± 0.3 × 107 down to 2 × 106 ± 0.8 × 106 CFU/mL. Dose-dependent effects of tetracycline were noted for perturbations of tetB and tetD gene expression and changes in acetate and propionate concentrations. Although no-observed-adverse-effect concentrations differed, depending on the traditional cultures and the molecular analysis techniques used, this in vitro continuous flow bioreactor study contributes to the knowledge base regarding the impact of chronic exposure of tetracycline on human intestinal microbiota. Full article
(This article belongs to the Special Issue Antibiotic Use in Veterinary)
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