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Advances in the Knowledge of Efficacy and Prudent Use of...
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Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Animal Physiology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 24674

Special Issue Editors

Dr. Ana M. Sahagun

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Institute of Biomedicine (IBIOMED), Veterinary Faculty, University of Leon, 24071 Leon, Spain
Interests: veterinary pharmacology; pharmacokinetics; antimicrobials and anthelmintic of veterinary use; drug–drug interactions
Dr. Raquel Diez

E-Mail Website
Guest Editor
Department of Biomedical Sciences, Institute of Biomedicine (IBIOMED), Veterinary Faculty, University of Leon, 24071 Leon, Spain
Interests: pharmacology; pharmacokinetics

Special Issue Information

Dear Colleagues,

Antimicrobials and anthelmintics are the most common veterinary medicines used to treat or prevent animal diseases. Indiscriminate and inappropriate use of these drugs can lead to the selection of resistant strains, which may imply a risk to animal or human health, also impacting the environment. This problem becomes even more important in farm animals, in which there is the possibility that small amounts of drugs or their metabolites remain in those animal products that enter the food chain. In the last decade, increasing efforts have been made to promote the prudent use of antimicrobial and anthelmintic drugs in veterinary medicine.

Original research papers on Pharmacokinetics and Pharmacodynamics that contribute to ensuring and improving the knowledge on the efficacy of these drugs in veterinary clinical practice, as well as those related to the design of appropriate dosage regimes, drug consumption, rational use of medicines, or others related to this topic are needed. Review articles are also welcome for this Special Issue.

Dr. Ana M. Sahagun
Dr. Raquel Diez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Animals is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antimicrobial drugs
  • anthelmintic drugs
  • efficacy
  • rational use
  • veterinary medicines

Published Papers (7 papers)

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Research

Jump to: Review

10 pages, 635 KiB  
Article
Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep
by Raquel Diez, M. Jose Diez, Juan J. Garcia, Jose M. Rodríguez, Cristina Lopez, Nelida Fernandez, Matilde Sierra and Ana M. Sahagun
Animals 2022, 12(4), 463; https://doi.org/10.3390/ani12040463 - 14 Feb 2022
Cited by 2 | Viewed by 3072
Abstract
The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole [...] Read more.
The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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20 pages, 3293 KiB  
Article
PK/PD Analysis by Nonlinear Mixed-Effects Modeling of a Marbofloxacin Dose Regimen for Treatment of Goat Mastitis Produced by Coagulase-Negative Staphylococci
by Augusto Matías Lorenzutti, Juan Pablo Vico, Juan Manuel Serrano-Rodríguez, Martín Alejandro Himelfarb, Manuel Ignacio San Andrés-Larrea, José Julio de Lucas-Burneo and Nicolás Javier Litterio
Animals 2021, 11(11), 3098; https://doi.org/10.3390/ani11113098 - 29 Oct 2021
Cited by 1 | Viewed by 1659
Abstract
Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for [...] Read more.
Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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12 pages, 984 KiB  
Article
Comparison of Short- versus Long-Course Antimicrobial Therapy of Uncomplicated Bacterial Pneumonia in Dogs: A Double-Blinded, Placebo-Controlled Pilot Study
by Aida I. Vientós-Plotts, Isabelle Masseau and Carol R. Reinero
Animals 2021, 11(11), 3096; https://doi.org/10.3390/ani11113096 - 29 Oct 2021
Cited by 4 | Viewed by 6193
Abstract
Current treatment for canine bacterial pneumonia relies on protracted courses of antimicrobials (3–6 weeks or more) with recommendations to continue for 1–2 weeks past resolution of all clinical and thoracic radiographic abnormalities. However, in humans, bacterial pneumonia is often treated with 5–10-day courses [...] Read more.
Current treatment for canine bacterial pneumonia relies on protracted courses of antimicrobials (3–6 weeks or more) with recommendations to continue for 1–2 weeks past resolution of all clinical and thoracic radiographic abnormalities. However, in humans, bacterial pneumonia is often treated with 5–10-day courses of antimicrobials, and thoracic radiographs are not considered useful to guide therapeutic duration. The primary study objective was to determine whether a short course of antimicrobials would be sufficient to treat canine bacterial pneumonia. Eight dogs with uncomplicated bacterial pneumonia were enrolled in this randomized, double-blinded, placebo-controlled study comparing clinical and radiographic resolution with differing durations of antimicrobial therapy. Dogs received a course of antimicrobials lasting 10 (A10) or 21 (A21) days. Dogs randomized to the A10 group received placebo for 11 days following antimicrobial therapy. Patients were evaluated at presentation and 10, 30 and 60 days after the initiation of antimicrobials. At 10 days, 6/8 dogs had resolution of both clinical signs and inflammatory leukogram, and 5/8 dogs had improved global radiographic scores. After 60 days, clinical and hematologic resolution of pneumonia was noted in all dogs regardless of antimicrobial therapy duration; however, 3/8 dogs had persistent radiographic lesions. Thoracic radiographs do not appear to be a reliable marker to guide antimicrobial therapy in canine bacterial pneumonia as radiographic lesions may lag or persist despite clinical cure. This pilot study suggests a 10-day course of antimicrobials may be sufficient to treat uncomplicated canine bacterial pneumonia. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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20 pages, 4221 KiB  
Article
Effect of Drinking Water Distribution System Design on Antimicrobial Delivery to Pigs
by Stephen Little, Andrew Woodward, Glenn Browning and Helen Billman-Jacobe
Animals 2021, 11(8), 2362; https://doi.org/10.3390/ani11082362 - 10 Aug 2021
Cited by 5 | Viewed by 2885
Abstract
On many pig farms, growing pigs are mass-medicated for short periods with antimicrobial drugs through their drinking water for metaphylaxis and to treat clinical disease. We conducted a series of four prospective observational cohort studies of routine metaphylactic in-water antibiotic dosing events on [...] Read more.
On many pig farms, growing pigs are mass-medicated for short periods with antimicrobial drugs through their drinking water for metaphylaxis and to treat clinical disease. We conducted a series of four prospective observational cohort studies of routine metaphylactic in-water antibiotic dosing events on a commercial pig farm, to assess the concentration of antimicrobial available to pigs throughout a building over time. Each dosing event was conducted by the farm manager with a differently designed looped water distribution system (WDS). We found that the antimicrobial concentration in water delivered to pigs at drinkers in each pen by a building’s WDS over time was profoundly influenced by the design of the WDS and the pigs’ water usage and drinking pattern, and that differences in the antimicrobial concentration in water over time at drinkers throughout a building could be eliminated through use of a circulator pump in a looped WDS. We also used a hydraulic WDS modelling tool to predict the antimicrobial concentration at drinkers over time during and after a dosing event. Our approach could be used to evaluate alternative in-water dosing regimens for pigs in a specific building in terms of their clinical efficacy and ability to suppress the emergence of antimicrobial resistance, and to determine the optimal regimen. The approach is applicable to all additives administered through drinking water for which the degree of efficacy is dependent on the dose administered. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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Review

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15 pages, 1531 KiB  
Review
Invited Review: Antimicrobial Use and Antimicrobial Resistance in Pathogens Associated with Diarrhea and Pneumonia in Dairy Calves
by Xin Zhang, Xia Yi, Haohua Zhuang, Zhaoju Deng and Chong Ma
Animals 2022, 12(6), 771; https://doi.org/10.3390/ani12060771 - 18 Mar 2022
Cited by 6 | Viewed by 2595
Abstract
Antimicrobial use (AMU) is the major driver of antimicrobial resistance (AMR) among bacteria in dairy herds. There have been numerous studies on AMU and AMR in dairy cows; however, studies on AMU and AMR in dairy calves are limited. A comprehensive overview of [...] Read more.
Antimicrobial use (AMU) is the major driver of antimicrobial resistance (AMR) among bacteria in dairy herds. There have been numerous studies on AMU and AMR in dairy cows; however, studies on AMU and AMR in dairy calves are limited. A comprehensive overview of the current state of knowledge of AMU and AMR among pathogens in dairy calves is important for the development of scientifically supported and applicable measures to curb antimicrobial use and the increasing risk of AMR. Therefore, we performed a systematic review of research on AMU and AMR in dairy calves. A total of 75 publications were included, of which 19 studies reported AMU data for dairy calves and 68 described AMR profiles of the four most prevalent bacteria that are associated with calf diarrhea and calf pneumonia. Large variation in AMU was found among herds across different regions. There seems to be a positive association between exposure to antimicrobials and occurrence of resistance. Most AMU was accounted for by treatment of diseases, while a small proportion of AMU was prophylactic. AMU was more common in treating calf diarrhea than in treating pneumonia, and the resistance rates in bacteria associated with diarrhea were higher than those in pathogens related to pneumonia. Organic farms used significantly fewer antimicrobials to treat calf disease; however, the antimicrobial resistance rates of bacteria associated with calf diarrhea and pneumonia on both types of farms were comparable. Feeding waste or pasteurized milk was associated with a higher risk of AMR in pathogens. Altogether, this review summarizes AMU and AMR data for dairy calves and suggests areas for future research, providing evidence for the design of antimicrobial use stewardship programs in dairy calf farming. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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32 pages, 2223 KiB  
Review
Rational Pharmacotherapy in Infectious Diseases: Issues Related to Drug Residues in Edible Animal Tissues
by Lucila Canton, Carlos Lanusse and Laura Moreno
Animals 2021, 11(10), 2878; https://doi.org/10.3390/ani11102878 - 01 Oct 2021
Cited by 14 | Viewed by 3929
Abstract
Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs [...] Read more.
Drugs are used in veterinary medicine to prevent or treat animal diseases. When rationally administered to livestock following Good Veterinary Practices (GVP), they greatly contribute to improving the production of food of animal origin. Since humans can be exposed chronically to veterinary drugs through the diet, residues in food are evaluated for effects following chronic exposures. Parameters such as an acceptable daily intake (ADI), the no-observed-adverse-effect level (NOAEL), maximum residue limits (MRLs), and the withdrawal periods (WPs) are determined for each drug used in livestock. Drug residues in food exceeding the MRLs usually appear when failing the GVP application. Different factors related either to the treated animal or to the type of drug administration, and even the type of cooking can affect the level of residues in edible tissues. Residues above the MRLs can have a diverse negative impact, mainly on the consumer’s health, and favor antimicrobial resistance (AMR). Drug residue monitoring programmes are crucial to ensure that prohibited or authorized substances do not exceed MRLs. This comprehensive review article addresses different aspects of drug residues in edible tissues produced as food for human consumption and provides relevant information contributing to rational pharmacotherapy in food-producing animals. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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21 pages, 3901 KiB  
Review
The Pattern of Blood–Milk Exchange for Antiparasitic Drugs in Dairy Ruminants
by Fernanda Imperiale and Carlos Lanusse
Animals 2021, 11(10), 2758; https://doi.org/10.3390/ani11102758 - 22 Sep 2021
Cited by 5 | Viewed by 2646
Abstract
The prolonged persistence of milk residual concentration of different antiparasitic drugs in lactating dairy animals should be considered before recommending their use (label or extra-label) for parasite control in dairy animals. The partition blood-to-milk ratio for different antiparasitic compounds depends on their ability [...] Read more.
The prolonged persistence of milk residual concentration of different antiparasitic drugs in lactating dairy animals should be considered before recommending their use (label or extra-label) for parasite control in dairy animals. The partition blood-to-milk ratio for different antiparasitic compounds depends on their ability to diffuse across the mammary gland epithelium. The high lipophilicity of some of the most widely used antiparasitic drugs explains their high partition into milk and the extended persistence of high residual concentrations in milk after treatment. Most of the antiparasitic drug compounds studied were shown to be stable in various milk-related industrial processes. Thus, the levels of residues detected in raw milk can be directly applicable to estimating consumer exposure and dietary intake calculations when consuming heat-processed fluid milk. However, after milk is processed to obtain milk products such as cheese, yogurt, ricotta, and butter, the residues of lipophilic antiparasitic drugs are higher than those measured in the milk used for their elaboration. This review article contributes pharmacokinetics-based information, which is useful to understand the relevance of rational drug-based parasite control in lactating dairy ruminants to avoid undesirable consequences of residual drug concentrations in milk and derived products intended for human consumption. Full article
(This article belongs to the Special Issue Advances in the Knowledge of Efficacy and Prudent Use of Antimicrobials and Anthelmintics)
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