Antibiotic Use in Veterinary

Abstract

Since the introduction of antibiotics in the 1930s, the form and philosophy of their use has changed considerably [...]

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Citation: Andres, M.S. Antibiotic Use
in Veterinary. Antibiotics 2022,11,
1539. https://doi.org/10.3390/
antibiotics11111539
Received: 19 October 2022
Accepted: 28 October 2022
Published: 3 November 2022
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antibiotics
Editorial
Antibiotic Use in Veterinary
Manuel San Andres
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine,
Universidad Complutense de Madrid, 28040 Madrid, Spain; misanand@vet.ucm.es
Since the introduction of antibiotics in the 1930s, the form and philosophy of their use
has changed considerably. After an initial phase of great hope, a new front for the control
and even the eradication of infectious diseases was opening up. In fact, one of the most
infamous quotes in the history of biomedicine is: “It is time to close the book on infectious
diseases, and declare the war against pestilence won.” This was long attributed to the United
States Surgeon General, Dr. William H. Stewart (1965–1969); however, the primary source
for the quote has never been identified. In recent years, that euphoria has been met with
a harsh reality: a "gap" in the discovery of new antibiotics since 1990 and the exponential
growth of resistance.
At this time, there are many agencies and public and private organizations that alert
and offer recommendations for dealing with the problem of antibiotic resistance. Specifi-
cally, the European Union, through the REGULATION (EU) 2019/6 OF THE EUROPEAN
PARLIAMENT AND OF THE COUNCIL, states that Antimicrobial resistance to medicinal
products for human use and veterinary medicinal products is a growing health problem in the Union
and worldwide. Due to the complexity of the problem, its cross-border dimension and the high
economic burden, its impact goes beyond its severe consequences for human and animal health and
has become a global public health concern that affects the whole of society and requires urgent and
coordinated intersectoral action in accordance with the ‘One Health’ approach
Nowadays, there is a high degree of awareness about the appropriate use of antibiotics
in livestock farming, but not so much about the non-appropriate use of antibiotics in pets
and the risk this poses to public health.
This Special Issue invited papers by experts working on antibiotic resistance, in very
diverse fields, showing different aspects with involvement in the One Health concept.
The studies by Grakh et al. and Sani Ismaila et al. evaluated the causes of the inappro-
priate use of antibiotics in small animal clinics in areas as disparate as India, Trinidad, and
Jamaica [
1
,
2
]. They show how the indiscriminate usage and overuse of antimicrobials in
pets or companion animals are underlying causes of antimicrobial resistance; the reasons
are incomplete courses of antibiotics, inappropriate follow-ups, the improper care of sick
animals, the self-prescription of antimicrobials by owners, unavailability of antibiogram
facilities, and the statement of an empirical treatment based on their experience as the main
criteria for antimicrobial choice in the absence of timely results from the laboratory or the
lack of use of standard antimicrobial protocols, which could be due, in some cases, to the
limited availability of resources.
In the paper by Melgarejo et al., the AMR-gene presence in microorganisms recovered
from urine from clinically healthy dogs is reported to highlight public health considerations
in the context of a species-spanning framework [
3
]. From the 30 AMR genes detected, the
most common AMR genes were aph(3
0
)Ia, and ermB, which confer resistance to aminogly-
cosides and MLS (macrolides, lincosamides, and streptogramins) antibiotics, respectively.
These AMR genes are mainly expressed in bacterial species such as Streptococcus,Staphy-
lococcus, and Corynebacterium genera. The presence of AMR genes that confer resistance
to clinical important antibiotics suggests that dogs may serve as reservoirs of clinically
relevant resistomes.
Antibiotics 2022,11, 1539. https://doi.org/10.3390/antibiotics11111539 https://www.mdpi.com/journal/antibiotics

Antibiotics 2022,11, 1539 2 of 3
In a similar field, the contribution from Ahn et al. determines the effects of tetracycline
at chronic subinhibitory exposure levels on human intestinal microbiota using an
in vitro
continuous flow bioreactor [
4
]. With this technique, they show that dose-dependent effects
of tetracycline were observed as perturbations of tetB and tetD gene expression and changes
in acetate and propionate concentrations. This contributes to knowledge on the impact of
the chronic exposure of tetracycline on human intestinal microbiota.
The following articles deal with different factors that can affect the more rational and
appropriate use of antibiotics and the causes that can influence their management.
Lorenzutti et al. describe the effect of a fluoroquinolone (marbofloxacin) on S. aureus
isolated from mastitis goat milk by different approaches as the minimum inhibitory and
bactericidal concentrations (MICs and MBCs) in cation-adjusted Mueller–Hinton broth
(CAMHB) and the serum and milk of goats at two inoculum sizes of 10
5
and 10
8
CFU/mL,
respectively [
5
]. The authors analyzed the time kill curves (TKC) using non-linear mixed
effect models in each growth medium and inoculum size, as well as the estimation of their
pharmacokinetic/pharmacodynamic (PK/PD) cut-off values. The results obtained indicate
that MIC values and PK/PD cut-off values to achieve clinical efficacy were highly depen-
dent on the inoculum and growth media, suggesting that further studies are necessary to
evaluate and optimize the best therapeutic strategies for treating S. aureus in lactating goats.
On the other hand, Nihat Ural and K. Uney studied the influence of the co-administration
of fluoroquinolone (danofloxacin) with meloxicam in healthy lambs and lambs with res-
piratory infections [
6
]. The results show that co-administration with meloxicam reduces
the clearance and volume of distribution, whereas AUC and Cmax are increased in in-
fected lambs. Additionally, this co-administration can provide optimum values of
ƒ
AUC0–
24/MIC (>56 h) and
ƒ
Cmax/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.
The study by Waxman et al. provides information about the intramuscular phar-
macokinetics of enrofloxacin in black vultures (Coragyps atratus) to dispose the necessary
knowledge to avoid extrapolation from other species and the derived risks [
7
]. Using previ-
ously published MIC values, the authors performed a PK/PD analysis, with cumulative
fraction responses obtained after Monte Carlo simulation for AUC/MIC > 30, 50, and 125,
and Cmax/MIC for E. coli and Mycoplasma synoviae. The results indicate that the doses
used could be appropriate to treat infectious diseases caused by Gram-positive bacteria
with MIC values lower than 1
µ
g/mL; however, plasma concentrations were insufficient to
reach the established Gram-negative breakpoints.
Finally, in an additional line of alternative methods to improve the state of health and
immunity, and therefore, the ability to respond to infections in cattle, Grossi et al. studied
the effect of a nutraceutical mixture, based on live yeast, mannan-oligosaccharides, and
organic selenium [
8
]. To this end, they carried out studies monitoring the incidence of
bovine respiratory disease and other health issues, as well as the mortality rate.
In the treatment group, the occurrence of bovine respiratory disease tended to be
reduced and the BHV-1 antibody production after vaccination was significantly improved,
as was the bactericidal activity. Additionally, the average daily gain and final weight were
significantly improved. Therefore, these results suggest that the nutraceutical mixture can
support the animal’s immune systems, improving its ability to react against pathogens, as
well as the feed efficiency and growth performance during the whole fattening period.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.

Antibiotics 2022,11, 1539 3 of 3
References
1.
Grakh, K.; Mittal, D.; Kumar, T.; Thakur, S.; Panwar, D.; Singh, L.; Kumar, M.; Jindal, N. Attitude, Opinions, and Working
Preferences Survey among Pet Practitioners Relating to Antimicrobials in India. Antibiotics
2022
,11, 1289. [CrossRef] [PubMed]
2.
Ismaila, M.S.; Thomas-Rhoden, A.; Neptune, A.; Sookram, K.; Gopaul, S.; Padarath, T.; Persad, A.; Georges, K.; Sundaram, V.
A Survey on the Rationale Usage of Antimicrobial Agents in Small Animal Clinics and Farms in Trinidad and Jamaica. Antibiotics
2022,11, 885. [CrossRef] [PubMed]
3.
Melgarejo, T.; Sharp, N.; Krumbeck, J.A.; Wu, G.; Kim, Y.J.; Linde, A. The Urinary Resistome of Clinically Healthy Companion
Dogs: Potential One Health Implications. Antibiotics 2022,11, 780. [CrossRef] [PubMed]
4.
Ahn, Y.; Jung, J.; Kweon, O.; Veach, B.; Khare, S.; Gokulan, K.; Piñeiro, S.; Cerniglia, C. Impact of Chronic Tetracycline Exposure
on Human Intestinal Microbiota in a Continuous Flow Bioreactor Model. Antibiotics 2021,10, 886. [CrossRef] [PubMed]
5.
Lorenzutti, A.M.; Andrés-Larrea, M.I.S.; Fernández-Varón, E.; Zarazaga, M.D.P.; Molina-López, A.M.; Serrano-Rodríguez, J.M.
Effects of Growth Medium and Inoculum Size on Pharmacodynamics Activity of Marbofloxacin against Staphylococcus aureus
Isolated from Caprine Clinical Mastitis. Antibiotics 2021,10, 1290. [CrossRef]
6.
Ural, M.N.; Uney, K. Pharmacokinetic Behavior and Pharmacokinetic/Pharmacodynamic Integration of Danofloxacin Following
Single or Co-Administration with Meloxicam in Healthy Lambs and Lambs with Respiratory Infections. Antibiotics
2021
,10, 1190.
[CrossRef] [PubMed]
7.
Waxman, S.; de Lucas, J.; Wiemeyer, G.; Bianchini, L.T.; Andrés, M.S.; Rodríguez, C. Pharmacokinetic Behaviour of Enrofloxacin
after Single Intramuscular Dosage in American Black Vultures (Coragyps atratus). Antibiotics 2021,10, 957. [CrossRef] [PubMed]
8.
Grossi, S.; Dell’Anno, M.; Rossi, L.; Compiani, R.; Rossi, C.A.S. 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. Antibiotics 2021,10, 1114. [CrossRef]