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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Anim. Sci.</journal-id>
<journal-title>Frontiers in Animal Science</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Anim. Sci.</abbrev-journal-title>
<issn pub-type="epub">2673-6225</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fanim.2025.1537853</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Animal Science</subject>
<subj-group>
<subject>Mini Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Use of soybean meal-based moxifloxacin pellets in equine nutrition and health</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Velazquez</surname>
<given-names>Desiderio Rodriguez</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Guerrero</surname>
<given-names>Jorge Antonio Varela</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
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<contrib contrib-type="author">
<name>
<surname>Alvarado</surname>
<given-names>Tonantzin D&#xed;az</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
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</contrib>
<contrib contrib-type="author">
<name>
<surname>Orozco</surname>
<given-names>Diego Gir&#xf3;n</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Salem</surname>
<given-names>Abdelfattah Zeidan Mohamed</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2119981/overview"/>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Kreuzer-Redmer</surname>
<given-names>Susanne</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1557017/overview"/>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Elghandour</surname>
<given-names>Mona Mohamed Yasseen</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
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</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Facultad de Medicina Veterinaria y Zootecnia. Universidad Aut&#xf3;noma del Estado de M&#xe9;xico</institution>, <addr-line>Toluca</addr-line>, <country>Mexico</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Facultad de Ciencias Agr&#xed;colas. Universidad Aut&#xf3;noma del Estado de M&#xe9;xico</institution>, <addr-line>Toluca</addr-line>, <country>Mexico</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Centre for Animal Nutrition and Welfare, University of Veterinary Medicine Vienna</institution>, <addr-line>Vienna</addr-line>, <country>Austria</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited by: James Levi Klotz, United States Department of Agriculture, United States</p>
</fn>
<fn fn-type="edited-by">
<p>Reviewed by: Jazmine Skinner, University of Southern Queensland, Australia</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Abdelfattah Zeidan Mohamed Salem, <email xlink:href="mailto:salem@uaemex.mx">salem@uaemex.mx</email>; Susanne Kreuzer-Redmer, <email xlink:href="mailto:susanne.kreuzer-redmer@vetmeduni.ac.at">susanne.kreuzer-redmer@vetmeduni.ac.at</email>; Mona Mohamed Yasseen Elghandour, <email xlink:href="mailto:mmohamede@uaemex.mx">mmohamede@uaemex.mx</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>22</day>
<month>04</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>6</volume>
<elocation-id>1537853</elocation-id>
<history>
<date date-type="received">
<day>01</day>
<month>12</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>31</day>
<month>03</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2025 Velazquez, Guerrero, Alvarado, Orozco, Salem, Kreuzer-Redmer and Elghandour</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Velazquez, Guerrero, Alvarado, Orozco, Salem, Kreuzer-Redmer and Elghandour</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<p>Pellets formulated from organic biomass, such as soybean meal, are increasingly used in animal nutrition and controlled drug delivery systems. This review aims to explore the advancements and challenges in developing and evaluating soybean meal-based moxifloxacin pellets specifically for equine applications. The focus includes production techniques, the role of soybean meal in equine diets, and the therapeutic potential of moxifloxacin. Soybean meal, known for its high protein and lysine content, is a valuable feed component for equines and offers advantages in pellet formulation. Moxifloxacin, a broad-spectrum antibiotic, has shown effectiveness in treating a range of bacterial infections in horses, with the added benefit of controlled release when delivered in pellet form. This combination presents a novel strategy for improving both nutrition and targeted medication in equines. However, further research is required to assess its safety and therapeutic efficacy.</p>
</abstract>
<kwd-group>
<kwd>moxifloxacin pellets</kwd>
<kwd>soybean meal</kwd>
<kwd>equine</kwd>
<kwd>bacterial infection</kwd>
<kwd>antibiotics</kwd>
</kwd-group>
<counts>
<fig-count count="4"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="66"/>
<page-count count="10"/>
<word-count count="4970"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Animal Nutrition</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1" sec-type="intro">
<label>1</label>
<title>Introduction</title>
<p>In the field of nutrition and veterinary medicine, the combination of technology and biotechnology has led to promising innovations. Among them, compacted biomass pellets emerge as an efficient and sustainable solution, with applications ranging from animal feed to drug delivery. Pellets, which are small cylinders of organic biomass, not only provide an economical and environmentally friendly way to feed animals of various species, but also facilitate the development of controlled-release formulations for drugs (<xref ref-type="bibr" rid="B24">Ghebre, 2022</xref>).</p>
<p>Dehydration of forage for pelleting offers additional benefits by allowing higher dry matter concentration and minimizing loss through microbial decomposition. Agricultural residues, such as soybean meal, have established themselves as a valuable protein source, especially in pig and poultry feed, due to their high protein content and their ability to be processed to eliminate potential toxic factors (<xref ref-type="bibr" rid="B5">Barrientos, 2010</xref>; <xref ref-type="bibr" rid="B29">Inyang et&#xa0;al., 2019</xref>). Soybean meal stands out not only for its nutritional value, but also for its absorptive properties, which make it suitable for applications in the removal of heavy metals and chemicals (<xref ref-type="bibr" rid="B17">Daneshvar et&#xa0;al., 2002</xref>). In the equine context, soybean meal is particularly useful due to its lysine content, an essential amino acid for tissue growth and repair (<xref ref-type="bibr" rid="B17">Daneshvar et&#xa0;al., 2002</xref>; <xref ref-type="bibr" rid="B10">Bockisch et&#xa0;al., 2023</xref>).</p>
<p>In parallel, moxifloxacin, a potent antibiotic of the fluoroquinolone class, has been shown to be effective against a wide range of bacterial infections, including those affecting equines. Its advanced chemical structure gives it a broad spectrum of action and high efficacy in inhibiting bacterial replication (<xref ref-type="bibr" rid="B23">Gardner et&#xa0;al., 2004</xref>). However, the administration of moxifloxacin in equines presents challenges related to drug stability, controlled release and precise dosing (<xref ref-type="bibr" rid="B44">OMS, 2020</xref>).</p>
<p>The integration of moxifloxacin into soybean meal-based pellets represents an innovative strategy to improve drug delivery in equines, ensuring controlled and effective release of the antibiotic. However, this approach requires careful evaluation of its stability, acceptability by animals and compliance with safety regulations to avoid adverse effects and the development of bacterial resistance (<xref ref-type="bibr" rid="B28">Humma and Patel, 2024</xref>).</p>
<p>The combination of soybean meal pellets with moxifloxacin offers an opportunity to optimize treatment administration in equines, improving efficiency and sustainability in veterinary practice. Continued research in this field is essential to overcome the challenges and maximize the benefits of this innovative solution. Therefore, this review discusses the development and evaluation of soybean meal-based moxifloxacin pellets for equine applications, focusing on production techniques, the role of soybean meal in equine diets, the therapeutic potential of moxifloxacin, and the advantages of its controlled release in pellet form. By integrating nutrition and drug delivery, this approach presents a novel strategy for improving both equine health and treatment efficiency. However, further research is needed to ensure its safety, efficacy, and regulatory compliance.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Pellets</title>
<p>Pellets are tiny cylinders of compacted biomass, usually made from organic materials, and are used as animal feed. This product is both ecological, sustainable and economical, and offers a wide range&#xa0;of applications (<xref ref-type="bibr" rid="B24">Ghebre, 2022</xref>). Pellets are produced by extrusion-spheronization, with subsequent coating. This method offers significant advantages for the development of enteric formulations and the controlled release of active ingredients, making it suitable for both monogastric and ruminant animals (<xref ref-type="bibr" rid="B38">Medrano, 2005</xref>).</p>
<p>Forage dehydration for pelletization optimizes preservation by increasing dry matter content and reducing the proliferation of degradative microorganisms by limiting water availability. This&#xa0;process enhances stability, preserves nutritional value, and facilitates storage and processing in pellet form (<xref ref-type="bibr" rid="B5">Barrientos, 2010</xref>). Agricultural waste or excluded biomass is used as various bioabsorbents in the elimination of heavy metals and chemicals present in wastewater, such as soybean meal (<xref ref-type="bibr" rid="B35">Magesh et&#xa0;al., 2020</xref>).</p>
<sec id="s2_1">
<label>2.1</label>
<title>Use of pellets in equines</title>
<p>Through pelleting, it has been possible to mold a mixture of ingredients, which once compacted in a cylindrical or spherical form are called pellets (<xref ref-type="bibr" rid="B32">Loor, 2016</xref>). The use of pellets has become a key element in the commercial manufacture of equine feed since their granular form simplifies their handling (<xref ref-type="bibr" rid="B41">Muhammad, 2024</xref>). In addition, they can be produced using agricultural by-products, which represents an option for their use (<xref ref-type="bibr" rid="B33">L&#xf3;pez, 2017</xref>). Among the advantages of using pellets in equines are that they help improve the digestibility of nutrients, reduce energy during feed consumption, prevent nutrient selection, reduce waste in feeders and improve economic reward and productive parameters (<xref ref-type="bibr" rid="B32">Loor, 2016</xref>). <xref ref-type="bibr" rid="B57">Soto and Rojas (2016)</xref> evaluated the potential replacement of balanced feed with <italic>Stylosanthes multilinea</italic> pellets in equines, using incremental inclusion levels of 0, 15, 30, and 45%. The results indicated that replacing up to 45% of the balanced feed with pellets did not produce significant effects on apparent digestibility, dry matter content, or crude protein concentration of the total ration. In a study conducted by <xref ref-type="bibr" rid="B14">Christ et al. (2020)</xref>, the use of wood pellets as bedding material in individual horse stalls was evaluated and compared to wheat straw. The results indicated that, from an economic perspective, the use of wood pellets reduces costs. Additionally, it was observed that horses housed on this type of bedding spent less time searching for food. Pellets used in equine nutrition are highly palatable, which is one of&#xa0;their key advantages. <xref ref-type="bibr" rid="B54">Ryon et&#xa0;al. (2023)</xref> evaluated the palatability&#xa0;of&#xa0;pellets formulated with <italic>Cannabis sativa</italic>, soybean meal, beet pulp, and rice bran. Their findings indicated that all formulations were well accepted by horses, with those containing <italic>Cannabis sativa</italic> exhibiting the highest palatability compared to the other formulations. <xref ref-type="bibr" rid="B60">Symoens et&#xa0;al. (2024)</xref> recently compared the effectiveness of steamed hay and alfalfa pellets in enhancing pulmonary function and reducing inflammation in horses with severe asthma. Their findings showed that alfalfa&#xa0;pellets reduced the weighted clinical scores from 13 to 2, whereas steamed hay just lowered the scores from 10 to 6.</p>
</sec>
</sec>
<sec id="s3">
<label>3</label>
<title>Soybean meal</title>
<p>Soybean meal is currently considered the protein source of choice for feeding growing and finishing pigs and poultry due to its high protein content (37.5%), high digestibility (82%), good balance of amino acids, consistent quality, and low costs compared to other protein sources. Soybean meal is a by-product of soybean oil extraction, produced through a combination of pressure and solvent extraction, followed by thermal treatment of the seeds (<xref ref-type="bibr" rid="B45">Ovuchimeru, 2020</xref>) Raw soybean seeds contain various antinutritional factors, including trypsin inhibitors, hemagglutinins, saponins, and a vitamin A inhibitory factor. However, these compounds are temperature-sensitive and can be effectively eliminated through proper processing (<xref ref-type="bibr" rid="B29">Inyang et&#xa0;al., 2019</xref>).</p>
<sec id="s3_1">
<label>3.1</label>
<title>Absorptive properties</title>
<p>Soybean flour exhibits absorbent properties due to its chemical composition, which includes a variety of functional groups and components that facilitate the adsorption of various substances. Among its main absorbent properties, it stands out for its ability to adsorb liquids, particularly water, due to the presence of polysaccharides such as cellulose and hemicellulose, which form bonds with water molecules, thus enabling moisture absorption. Within this liquid adsorption property, its ability to absorb oils and fats is also notable, owing to its high concentration of proteins and fiber (<xref ref-type="bibr" rid="B27">Huang et&#xa0;al., 2024</xref>).</p>
<p>Additionally, soybean flour exhibits absorption properties mediated by functional groups such as amino (-NH2) and carboxyl (-COOH), which can interact with various substances through electrostatic interactions. These characteristics give soybean flour the ability to: (i) absorb and retain essential nutrients, such as amino acids, proteins, and minerals, along the digestive tract, and (ii) absorb toxic compounds or contaminants, such as certain heavy metals, through an ion-exchange mechanism (<xref ref-type="bibr" rid="B17">Daneshvar et&#xa0;al., 2002</xref>). These properties make soybean flour a promising material for antibiotic adsorption, particularly due to its low cost and widespread use in animal feed.</p>
</sec>
<sec id="s3_2">
<label>3.2</label>
<title>Soybean meal in equine feed</title>
<p>The equine is a monogastric herbivore with a relatively small stomach, however, it has a well-developed and functional cecum and colon. Its digestive process is fundamentally enzymatic from the mouth to the terminal part of the ileum and to a lesser degree in the cecum and colon where the fermentation of crude fiber and other nutrients takes place with 70% of the efficiency of ruminants (<xref ref-type="bibr" rid="B2">Arrieta et&#xa0;al., 2007</xref>). They have developed their cecum where a large number of microorganisms are housed, which break down the cellulose that cannot be digested in the upper digestive tract. Volatile fatty acids are produced in the cecum and absorbed as a source of energy (<xref ref-type="bibr" rid="B37">Mart&#xed;nez Mar&#xed;n, 2008</xref>).</p>
<p>Soybean meal is one of the primary protein sources due to its high lysine content. This essential amino acid plays a crucial role in foal growth, as horses cannot synthesize it on their own. Lysine is vital for tissue generation and repair, making it particularly important for growing foals, which require more protein than mature horses (<xref ref-type="bibr" rid="B10">Bockisch et&#xa0;al., 2023</xref>). When horses lack access to pasture and their diet primarily consists of cereals, lysine deficiency becomes more pronounced, reducing the overall quality of the ingested protein (<xref ref-type="bibr" rid="B26">Hoyos et&#xa0;al., 2022</xref>).</p>
</sec>
</sec>
<sec id="s4">
<label>4</label>
<title>Moxifloxacin</title>
<p>Moxifloxacin, a potent fluoroquinolone antibiotic developed by Bayer AG and approved by the FDA in 1999, is effective against a variety of bacterial infections, especially respiratory infections, and is a valuable addition to the antibiotic armamentarium because of its broad spectrum of action (<xref ref-type="bibr" rid="B39">Meena et&#xa0;al., 2019</xref>). Moxifloxacin is highly effective against a variety of bacterial infections. It is approved by the FDA to treat community-acquired pneumonia caused by susceptible strains of <italic>Streptococcus pneumoniae</italic> and <italic>Mycoplasma pneumoniae</italic>, acute bacterial sinusitis, bacterial exacerbations of chronic bronchitis, and complicated skin and cutaneous tissue infections (<xref ref-type="bibr" rid="B28">Humma and Patel, 2024</xref>) (<xref ref-type="fig" rid="f1">
<bold>Figure&#xa0;1</bold>
</xref>).</p>
<fig id="f1" position="float">
<label>Figure&#xa0;1</label>
<caption>
<p>Chemical structure of moxifloxacin, synthetic antimicrobial agent, fourth generation fluoroquinolone due to its methoxy group at position 8 (Made with <ext-link ext-link-type="uri" xlink:href="https://biomodel.uah.es/en/DIY/JSME/draw.es.htm">https://biomodel.uah.es/en/DIY/JSME/draw.es.htm</ext-link>).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fanim-06-1537853-g001.tif"/>
</fig>
<sec id="s4_1">
<label>4.1</label>
<title>Pharmacology and mechanisms of action of moxifloxacin</title>
<p>Clinically used quinolones have a two-ring structure, with nitrogen at the 1-position, a carbonyl group at the 4-position and a carboxyl group at the 3-position (<xref ref-type="bibr" rid="B40">Millanao et&#xa0;al., 2021</xref>). The potency and spectrum are significantly increased when a fluorine atom is attached at the 6-position, possibly because of improved tissue penetration and binding to bacterial topoisomerases (<xref ref-type="bibr" rid="B1">Al&#xf3;s, 2009</xref>), see <xref ref-type="fig" rid="f2">
<bold>Figure&#xa0;2</bold>
</xref>. Antibiotics of the fluoroquinolone class show excellent activity against Gram-negative aerobes including Enterobacteria, <italic>Pseudomonas aeruginosa</italic>, <italic>Mycoplasma</italic> spp., <italic>Rikettsia</italic> spp. and <italic>Escherichia</italic> spp. (<xref ref-type="bibr" rid="B18">de Jes&#xfa;s, 2007</xref>). It should be noted that Gram-negative bacteria possess an outer membrane that is often a permeability barrier to an antibiotic molecule as it surrounds the peptidoglycan layer of the cell wall and as a consequence, Gram-negative bacteria generally have reduced susceptibility to antibiotics compared to Gram-positive bacteria (<xref ref-type="bibr" rid="B31">Kuriyama et&#xa0;al., 2014</xref>). Compounds that carry a double ring derived from the pyrrolidone ring in position 7 increase their activity against Gram-positive bacteria; if they carry a methoxy group in position 8, their activity against anaerobes improves, which is the case of moxifloxacin and gatifloxacin, fourth-generation fluoroquinolones (<xref ref-type="bibr" rid="B1">Al&#xf3;s, 2009</xref>).</p>
<fig id="f2" position="float">
<label>Figure&#xa0;2</label>
<caption>
<p>When DNA gyrase is exposed to moxifloxacin, the drug interacts on the surface of the alpha-helical domain of the enzyme forming an irreversible complex of quinolone, gyrase, and DNA, preventing the progression of the replication fork and transcription complexes, leading to cell death (Own elaboration using Microsoft Office Power Point <uri xlink:href="https://biomodel.uah.es/en/DIY/JSME/draw.es.htm">https://biomodel.uah.es/en/DIY/JSME/draw.es.htm</uri> for the elaboration of the chemical structure of moxifloxacin and <uri xlink:href="https://smart.servier.com/">https://smart.servier.com/</uri> for the images).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fanim-06-1537853-g002.tif"/>
</fig>
<p>Moxifloxacin, like other quinolones, inhibits the bacterial enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for the replication, transcription, repair, and recombination of DNA and RNA in bacterial cells (<xref ref-type="bibr" rid="B12">Carrillo et&#xa0;al., 2018</xref>). When DNA gyrase is exposed to a quinolone, the drug interacts with the surface of the alpha-helical domain of the enzyme, compromising DNA anchoring and repair. Toxic effects occur through the formation of an irreversible complex formed by quinolone, gyrase, and DNA. This complex prevents replication fork progression and transcription complexes, leading to chromosome fragmentation and cell death (<xref ref-type="bibr" rid="B58">Stroman et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B36">Mar&#xed;n, 2008</xref>) (see <xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>).</p>
<fig id="f3" position="float">
<label>Figure&#xa0;3</label>
<caption>
<p>Effect of soybean meal pellet with moxifloxacin on digestive and metabolic levels in horses (Made with images from <ext-link ext-link-type="uri" xlink:href="https://www.biorender.com/">https://www.biorender.com/</ext-link>).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fanim-06-1537853-g003.tif"/>
</fig>
<p>Moxifloxacin has a slightly different chemical structure from older veterinary fluoroquinolones by the 8-methoxy substitution. As a result of this modification, this new generation of drugs has broad-spectrum antimicrobial activity against Gram-positive bacteria and anaerobes (<xref ref-type="bibr" rid="B47">Papich, 2020</xref>). The fourth-generation quinolones (moxifloxacin, trovafloxacin), retain activity against microorganisms especially <italic>A. aureus</italic> and Enterococcus, <italic>S. pneumoniae</italic>, <italic>Klebsiella pneumoniae</italic>, <italic>Haemophilus influenzae</italic>, <italic>Legionella pneumophila</italic>, <italic>Moraxella catarrhalis</italic> and to a lesser extent <italic>Chlamydia pneumoniae</italic> and <italic>Mycoplasma</italic> pneumoniae (<xref ref-type="bibr" rid="B3">Balfour and Wiseman, 1999</xref>; <xref ref-type="bibr" rid="B16">Constantinou et&#xa0;al., 2007</xref>) being at least 2 to 8 times more potent than the first-generation quinolones (ofloxacin and ciprofloxacin) in their <italic>in vitro</italic> activity (<xref ref-type="bibr" rid="B52">Rolston et&#xa0;al., 2006</xref>). As stated by <xref ref-type="bibr" rid="B18">de Jes&#xfa;s (2007)</xref> and <xref ref-type="bibr" rid="B63">Valde&#x301;z-Cruz et al. (2013)</xref>, <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref> lists the majority of bacteria responsible for common diseases in equines, highlighting the <italic>in vitro</italic> activity of Moxifloxacin against them.</p>
<table-wrap id="T1" position="float">
<label>Table&#xa0;1</label>
<caption>
<p>
<italic>In vitro</italic> activity of Moxifloxacin in different strains bacterial.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="center">Moxifloxacin <break/>Concentration (MIC)</th>
<th valign="top" align="center">Bacterium</th>
<th valign="top" align="left">Gram <break/>positive/negative</th>
<th valign="top" align="left">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">0.25&#x2013;2 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Streptococcus pneumoniae</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B8">Blondeau and Hansen, 2001</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">.03&#x2013;8 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Staphilococcus aureus</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B49">Pong et&#xa0;al., 1999</xref>; <xref ref-type="bibr" rid="B25">Hoogkamp and Roelofs, 2000</xref>; <xref ref-type="bibr" rid="B8">Blondeau and Hansen, 2001</xref>; <xref ref-type="bibr" rid="B30">Kim et&#xa0;al., 2006</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.047&#x2013;32 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Pseudomonas aeruginosa</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B8">Blondeau and Hansen, 2001</xref>; <xref ref-type="bibr" rid="B30">Kim et&#xa0;al., 2006</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.125 &#xb5;g/mL</td>
<td valign="top" align="left">Coagulase negative Staphylococcus spp.</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">Kim et&#xa0;al., 2006</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.03&#x2013;0.12 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Rhodococcus equi</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.03&#x2013;4.0 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Enterococcus faecalis</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">1.0&#x2013;32.0 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Enterococcus faecium</italic>
</td>
<td valign="top" align="left">Positive</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B25">Hoogkamp and Roelofs, 2000</xref>; <xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.25 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Serratia marcescens</italic>
</td>
<td valign="top" align="left">Negative</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B30">Kim et&#xa0;al., 2006</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.0625 mg/L, 0.03&#x2013;128 mg/L</td>
<td valign="top" align="left">
<italic>Escherichia coli</italic>
</td>
<td valign="top" align="left">Negative</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B56">Singh et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B14">Christ et&#xa0;al., 2020</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.03&#x2013;1.0 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Klebsiella pneumoniae</italic>
</td>
<td valign="top" align="left">Negative</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>; <xref ref-type="bibr" rid="B22">Gao et&#xa0;al., 2019</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">&lt;0.25 mg/L</td>
<td valign="top" align="left">
<italic>Pasteurella</italic>spp.</td>
<td valign="top" align="left">Negative</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B43">Odenholt and Cars, 2006</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">0.03&#x2013;0.5 &#xb5;g/mL</td>
<td valign="top" align="left">
<italic>Salmonella</italic>spp.</td>
<td valign="top" align="left">Negative</td>
<td valign="top" align="left">(<xref ref-type="bibr" rid="B9">Blondeau et&#xa0;al., 2000</xref>; <xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Survival curves show that when the concentration of fluoroquinolones is close to the minimum inhibitory concentration (MIC) of the bacteria, the drug stops bacterial growth, however, when the concentration is increased in relation to the bacterial MICs, cell death increases up to a certain concentration of the drug (optimal bactericidal concentration), but an increase above this optimum can lead to a decrease in the bactericidal effect (<xref ref-type="bibr" rid="B36">Mar&#xed;n, 2008</xref>).</p>
<p>In respect to <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>, it is shown that moxifloxacin presented improved activity against penicillin-sensitive and -resistant pneumococci, a comparatively high activity against Gram-positive cocci and bacilli; likewise, better activity compared to ciprofloxacin and levofloxacin, reaching inhibition of more than 70% at concentrations of 1.0 &#x3bc;g/mL; it had similar activity against gram-negative organisms compared to the second and third generation of fluoroquinolones; it had a rapid elimination rate of fluoroquinolone-resistant organisms. On the other hand, although MICs give information about a specific antibiotic concentration that inhibits the growth of a bacterial strain, it does not distinguish between bactericidal or bacteriostatic effects, nor does <italic>in vitro</italic> activity imply <italic>in vivo</italic> efficacy, so the mutant prevention concentration (MPC) will be 8 to 10 times higher than the MIC, where the range of concentrations between MIC and MPC is defined as the mutant selection window. The MPC is an important concept to prevent the growth of organisms that have some level of drug resistance prior to therapy (<xref ref-type="bibr" rid="B49">Pong et&#xa0;al., 1999</xref>; <xref ref-type="bibr" rid="B55">Schedletzky et&#xa0;al., 1999</xref>; <xref ref-type="bibr" rid="B9">Blondeau et&#xa0;al., 2000</xref>; <xref ref-type="bibr" rid="B25">Hoogkamp and Roelofs, 2000</xref>; <xref ref-type="bibr" rid="B8">Blondeau and Hansen, 2001</xref>; <xref ref-type="bibr" rid="B51">Rolston et&#xa0;al., 2003</xref>; <xref ref-type="bibr" rid="B58">Stroman et&#xa0;al., 2005</xref>; <xref ref-type="bibr" rid="B30">Kim et&#xa0;al., 2006</xref>; <xref ref-type="bibr" rid="B43">Odenholt and Cars, 2006</xref>; <xref ref-type="bibr" rid="B52">Rolston et&#xa0;al., 2006</xref>; <xref ref-type="bibr" rid="B16">Constantinou et&#xa0;al., 2007</xref>; <xref ref-type="bibr" rid="B56">Singh et&#xa0;al., 2009</xref>; <xref ref-type="bibr" rid="B22">Gao et&#xa0;al., 2019</xref>).</p>
</sec>
<sec id="s4_2">
<label>4.2</label>
<title>Adverse effects of moxifloxacin in horses</title>
<p>There are few studies addressing the adverse effects of moxifloxacin use in horses. In a study by <xref ref-type="bibr" rid="B23">Gardner et al. (2004)</xref>, the efficacy of this antibiotic was evaluated against bacterial infections in horses, with an emphasis on its application in the treatment of pneumonia. The results showed that moxifloxacin has potent activity against key respiratory pathogens in horses. Despite its favorable characteristics, such as high systemic availability and a prolonged half-life, its use is not recommended for the treatment of equine bacterial pneumonia due to associated gastrointestinal side effects. In this study, four mares developed mild intermittent diarrhea, which began approximately 8 hours after the administration of the first dose of moxifloxacin. Additionally, one of the mares experienced a brief episode of colic 12 hours after the third dose. Toxins A and/or B from Clostridium difficile were isolated from the feces of the mare that exhibited the most severe diarrhea. These gastrointestinal side effects highlight the concerns associated with the use of moxifloxacin in the treatment of bacterial infections in horse.</p>
<p>In a study conducted by <xref ref-type="bibr" rid="B59">Sumano L&#xf3;pez et&#xa0;al. (2020)</xref> on adverse drug reactions in horses, it is noted that fluoroquinolones can induce joint damage in developing or immature animals. This finding suggests that these drugs should not be administered to young animals still in critical stages of bone development, such as growing horses and pregnant mares. These results highlight the importance of considering the age and developmental stage of the animal when evaluating the use of these medications to prevent significant adverse effects.</p>
</sec>
</sec>
<sec id="s5">
<label>5</label>
<title>The importance of formulating antibiotic pellets with soybean meal</title>
<p>Pelletizing costs vary depending on the physical characteristics of the ingredients. If the raw material includes fibrous elements such as bagasse, bran, or ground alfalfa, the pelleting machine requires more energy to compress these materials (<xref ref-type="bibr" rid="B41">Muhammad, 2024</xref>). On the other hand, if denser ingredients are used, such as grains and soybean meal, the compression process consumes less energy (<xref ref-type="bibr" rid="B32">Loor, 2016</xref>; <xref ref-type="bibr" rid="B41">Muhammad, 2024</xref>). Therefore, soybean meal pellets have already been developed for use in horse diets. <xref ref-type="table" rid="T2">
<bold>Table&#xa0;2</bold>
</xref> details the chemical composition of these soybean meal pellets (<xref ref-type="bibr" rid="B42">Nahashon and Kilonzo, 2011</xref>; <xref ref-type="bibr" rid="B46">Pacheco et&#xa0;al., 2013</xref>; <xref ref-type="bibr" rid="B48">Pettersson and Pontoppi, 2013</xref>; <xref ref-type="bibr" rid="B33">L&#xf3;pez, 2017</xref>; <xref ref-type="bibr" rid="B21">Frempong et&#xa0;al., 2019</xref>; <xref ref-type="bibr" rid="B34">Lyu et&#xa0;al., 2021</xref>; <xref ref-type="bibr" rid="B54">Ryon et&#xa0;al., 2023</xref>).</p>
<table-wrap id="T2" position="float">
<label>Table&#xa0;2</label>
<caption>
<p>Chemical composition of soybean meals.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="center">Reported unit/ Nutrient</th>
<th valign="top" align="center">DM</th>
<th valign="top" align="center">ME</th>
<th valign="top" align="center">CF</th>
<th valign="top" align="center">CF</th>
<th valign="top" align="center">CP</th>
<th valign="top" align="center">NFE</th>
<th valign="top" align="center">ADF</th>
<th valign="top" align="center">Ash</th>
<th valign="top" align="center">NDF</th>
<th valign="top" align="center">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="center">%</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">2.23 kcal/kg</td>
<td valign="top" align="center">7.0</td>
<td valign="top" align="center">0.8</td>
<td valign="top" align="center">44.0</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B42">Nahashon and Kilonzo, 2011</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">%</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">3.05 kcal/kg</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">5.79</td>
<td valign="top" align="center">21.0</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B46">Pacheco et&#xa0;al., 2013</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">g/kg dry matter</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">17&#x2013;21</td>
<td valign="top" align="center">490&#x2013;540</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B48">Pettersson and Pontoppi, 2013</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">%</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">48.8</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B33">L&#xf3;pez, 2017</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">%</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">12.61 (MJ/kg)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">8.34</td>
<td valign="top" align="center">21.24</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B21">Frempong et&#xa0;al., 2019</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">g/kg dry matter</td>
<td valign="top" align="center">884.3</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">49.9</td>
<td valign="top" align="center">11.9</td>
<td valign="top" align="center">549.7</td>
<td valign="top" align="center">203.4</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">6.94</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B34">Lyu et&#xa0;al., 2021</xref>)</td>
</tr>
<tr>
<td valign="top" align="center">%</td>
<td valign="top" align="center">89.8</td>
<td valign="top" align="center">2.85 (kcal/kg)</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">2.0</td>
<td valign="top" align="center">52.1</td>
<td valign="top" align="center">&#x2013;</td>
<td valign="top" align="center">7.7</td>
<td valign="top" align="center">7.4</td>
<td valign="top" align="center">12.0</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B54">Ryon et&#xa0;al., 2023</xref>)</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>DM, dry matter; CF, crude fibre; CF, crude fat; CP, crude protein; NFE, nitrogen-free extract; ADF, acid detergent fiber; NDF, neutral detergent fiber; -, not determined.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>In addition, pellets have been shown to improve animal nutrition by increasing nutrient and fat digestibility, reducing energy consumption during feeding, preventing ingredient selection by horses, having good acceptance, improving economic performance and optimizing production parameters (<xref ref-type="bibr" rid="B32">Loor, 2016</xref>; <xref ref-type="bibr" rid="B54">Ryon et&#xa0;al., 2023</xref>). <italic>In vitro</italic> studies of the antibacterial activity of moxifloxane have been performed on Gram-positive bacterial strains such as <italic>Streptococcus pneumoniae</italic>, <italic>Staphilococcus aureus</italic>, <italic>Pseudomonas. aeruginosa</italic>, <italic>S. equi</italic> sub spp. Zooepidemicus, Coagulase-negative <italic>Staphylococcus</italic> spp., <italic>Rhodococcus equi</italic>, <italic>Enterococcus faecalis</italic>, <italic>Enterococcus faecium</italic>; and Gram-negative strains <italic>Serratia marcescens</italic>, <italic>Escherichia coli</italic>, <italic>Klebsiella pneumoniae</italic>, <italic>Pasteurella</italic> spp., <italic>Salmonella</italic> spp. and <italic>Brucella</italic> spp. where the minimum inhibitory concentration to disable bacterial strains has been demonstrated. In addition, the FDA has approved this antibiotic for the treatment of pneumonia caused by <italic>Streptococcus pneumoniae</italic> and <italic>Mycoplasma pneumoniae</italic> (<xref ref-type="bibr" rid="B28">Humma and Patel, 2024</xref>). The use of moxifloxacin has been reported to inhibit the bacteria <italic>Streptococcus equinus</italic> (<xref ref-type="bibr" rid="B66">Zheng et&#xa0;al., 2024</xref>), which causes equine adenitis, this disease is an infection&#xa0;whose most common symptoms include fever (between 40 and 41&#xb0;C) and signs associated with fever such as loss of appetite, weakness, and muscle pain. Initially, inflammation of the regional&#xa0;lymph nodes, purulent nasal discharge, and severe pharyngitis are observed which can make swallowing difficult. Possible complications of this disease include sinusitis, mucopurulent infection in the guttural pouches (empyema), immune-mediated inflammation of blood vessels due to the high antigen load (hemorrhagic purpura), and abscesses in the thoracic and abdominal cavities, which are transmitted directly and indirectly through contact with mucopurulent secretions from infected horses, which represents a problem in the equine population (<xref ref-type="bibr" rid="B8">Blondeau and Hansen, 2001</xref>; <xref ref-type="bibr" rid="B33">L&#xf3;pez, 2017</xref>).</p>
<p>Therefore, soybean meal is a profitable and efficient option for the production of moxifloxacin pellets, which would have a dual purpose, which would be to improve animal nutrition and the administration of medication.</p>
</sec>
<sec id="s6">
<label>6</label>
<title>Indications and clinical uses of moxifloxacin in equines</title>
<p>Moxifloxacin is an advanced fluoroquinolone antibiotic (<xref ref-type="bibr" rid="B36">Mar&#xed;n, 2008</xref>) and potent activity against key respiratory pathogens of the horse (<xref ref-type="bibr" rid="B23">Gardner et&#xa0;al., 2004</xref>). Although it is a human drug, it has been used in animals for the treatment of infections refractory to other drugs, including ocular, cutaneous, and tissue infections (<xref ref-type="bibr" rid="B19">De&#xa0;Linde et&#xa0;al., 2014</xref>; <xref ref-type="bibr" rid="B39">Meena et&#xa0;al., 2019</xref>). The spectrum of activity includes Gram-positive cocci and anaerobic bacteria that may be resistant to other quinolones (<xref ref-type="bibr" rid="B47">Papich, 2020</xref>).</p>
<p>According to <xref ref-type="table" rid="T3">
<bold>Table&#xa0;3</bold>
</xref>, the proposed approach proved to be effective for the treatment of indolent ulcers in horses treated with moxifloxacin, in addition to the fact that corneal ulceration or ulcerative keratitis is a frequent reason for veterinary consultation in the equine clinic, since it involves ocular pain and vision defects (<xref ref-type="bibr" rid="B7">Blanco et&#xa0;al., 2016</xref>). There are few documented and published cases of the administration of moxifloxacin in horses, but as for other common diseases in equines, they are:</p>
<table-wrap id="T3" position="float">
<label>Table&#xa0;3</label>
<caption>
<p>Equine diseases treated with moxifloxacin.</p>
</caption>
<table frame="hsides">
<thead>
<tr>
<th valign="top" align="center">Clinical diagnosis</th>
<th valign="top" align="center">Age</th>
<th valign="top" align="center">Moxifloxacin dosage</th>
<th valign="top" align="center">Reference</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Corneal ulcer</td>
<td valign="top" align="left">2 geldings<break/>1 stallion<break/>3 mares, average age 9.3</td>
<td valign="top" align="left">Moxifloxacin 0.5% every 4 hours for 7 doses</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B15">Clode et&#xa0;al., 2010</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Kerachitis</td>
<td valign="top" align="left">9 adult mixed breed horses</td>
<td valign="top" align="left">Moxifloxacin 0.5%</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B65">Westermeyer et&#xa0;al., 2011</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Indolent ulcer.<break/>Severe blepharospasm and severe pain in the left eye</td>
<td valign="top" align="left">2 year old Quarter Horse</td>
<td valign="top" align="left">VIGAMOX 5 mg/ml eye drops based on moxifloxacin in solution and hyaluronic acid (Hyabak), both every 4/4 hours for 14 days</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B20">de Melo et&#xa0;al., 2018</xref>)</td>
</tr>
<tr>
<td valign="top" align="left">Stromal corneal abscess</td>
<td valign="top" align="left">16 year old male equine</td>
<td valign="top" align="left">Moxifloxacin (Vigamox) 3 drops every 2 hours</td>
<td valign="top" align="center">(<xref ref-type="bibr" rid="B13">Castellanos, 2019</xref>)</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>Brucellosis is a highly contagious zoonotic disease that affects a wide variety of domestic and wild animal species, including mainly cattle, pigs, horses, sheep, goats, and dogs, and is present worldwide. In the equine species, the occurrence of this disease is important, because these animals are potential hosts and contribute to the introduction of the disease in unaffected areas, as well as the maintenance where it is endemic (<xref ref-type="bibr" rid="B53">Rosero and Jim&#xe9;nez, 2016</xref>; <xref ref-type="bibr" rid="B62">Tique et&#xa0;al., 2016</xref>). Fluoroquinolones, whether first-generation or newer 8-methoxy derivatives, could be useful in the treatment of brucellosis (<xref ref-type="bibr" rid="B4">Barkai et&#xa0;al., 2004</xref>). Something that is also supported by the data in <xref ref-type="table" rid="T1">
<bold>Table&#xa0;1</bold>
</xref>.</p>
<p>Mumps are a highly contagious and serious infection of horses and other equines caused by the bacteria <italic>Streptococcus equi</italic>, however, there is debate among veterinarians as to whether to treat an animal with mumps with antibiotics. Gardner et&#xa0;al (<xref ref-type="bibr" rid="B23">Gardner et&#xa0;al., 2004</xref>),mentioned that according to the calculations in their study of pharmacokinetics/pharmacodynamic relationships, AUC/MIC and Cmax/MIC, predict clinical success for the treatment of most pathogenic respiratory diseases of the horse. On the other hand, Gao et&#xa0;al (<xref ref-type="bibr" rid="B22">Gao et&#xa0;al., 2019</xref>), propose moxifloxacin hybrids that decrease toxicity in cells and have greater bactericidal activity against antibiotic-resistant strains, as an alternative to solve the toxicity caused.</p>
<p>Although new fluoroquinolones are available, these should&#xa0;be reserved for resistant infections in order to avoid the development of multi-resistant microorganisms and, as with most antibiotic treatments, these should follow a precise analysis and diagnosis in order to avoid unnecessary treatment, considering the increase in antibiotic resistance rates (<xref ref-type="bibr" rid="B12">Carrillo et&#xa0;al., 2018</xref>) so complete care must be taken when medicating any animal, not just equines.</p>
<sec id="s6_1">
<label>6.1</label>
<title>Effect of the drug on digestive and metabolic levels in equines</title>
<p>Some factors that can influence digestion in equines are animal individuality, chemical composition of the feed, feeding capacity, type of work, physical form of the feed, physiological stage, water content of the feed, speed of transit of the feed in the digestive tract (48&#x2013;72 hours) and amount of fiber in the ration (<xref ref-type="bibr" rid="B64">Van Weyenberg et&#xa0;al., 2006</xref>). Equines present digestive physiology with determining characteristics such as efficient mastication, rapid gastric passage rate, intense enzymatic digestion in the small intestine, and prolonged microbial action in the large intestine (<xref ref-type="bibr" rid="B2">Arrieta et&#xa0;al., 2007</xref>). The digestive system of horses has adapted to be able to ingest large quantities of grass very evenly distributed throughout the day and to obtain energy efficiently from it. The enzymatic digestion of the feed releases glucose, amino acids and fatty acids for absorption. Additionally, the well-developed large intestine enables the acquisition of supplementary energy in the form of volatile fatty acids through the microbial fermentation of fiber and the fraction of the feed that is not enzymatically digested (<xref ref-type="bibr" rid="B37">Mart&#xed;nez Mar&#xed;n, 2008</xref>).</p>
<p>Fluoroquinolones are well absorbed after oral administration in animals with a single-chamber stomach and the newer ones tend to have a longer half-life. Most fluoroquinolones are metabolized in the liver; they are eliminated mainly through the kidneys, although some are excreted in bile (<xref ref-type="bibr" rid="B36">Mar&#xed;n, 2008</xref>; <xref ref-type="bibr" rid="B12">Carrillo et&#xa0;al., 2018</xref>) and the elimination pathways of moxifloxacin are balanced, not depending exclusively on renal or hepatic function. Moxifloxacin has a low plasma protein binding, approximately 40&#x2013;42%, which is important since only the free drug is active against the bacteria and can penetrate the target tissues. The plasma protein to which it mainly binds is albumin (<xref ref-type="bibr" rid="B11">Carretero Colomer, 2001</xref>). Its bioavailability is excellent and allows oral administration in most situations; this bioavailability is approximately 100%, it does not decrease with concomitant food intake, but gastrointestinal undesirable effects are the most frequent. They occur in 2&#x2013;20% of cases, depending on the molecules and situations, and constitute 50% of the side effects of fluoroquinolones (<xref ref-type="bibr" rid="B50">Revest and Tattevin, 2014</xref>) (<xref ref-type="fig" rid="f3">
<bold>Figure&#xa0;3</bold>
</xref>).</p>
</sec>
</sec>
<sec id="s7">
<label>7</label>
<title>Formation of pellets based on soy flour and moxifloxacin</title>
<p>
<xref ref-type="fig" rid="f4">
<bold>Figure&#xa0;4</bold>
</xref> presents a proposal for the formation of moxifloxacin pellets with soy flour for administration in horses, from the obtaining of soy flour and the antibiotic. For this, the methodology of <xref ref-type="bibr" rid="B41">Muhammad (2024)</xref> and <xref ref-type="bibr" rid="B32">Loor (2016)</xref> was taken as a reference. The process begins with the precise weighing and homogenization of the ingredients in the recommended proportions of 95% soybean flour and 5% moxifloxacin. During the steam conditioning phase, the combined application of heat, moisture, and pressure facilitates the gelatinization and homogenization of the mixture, optimizing its physicochemical properties for further processing. The ideal temperature for this stage ranges between 60 and 70&#xb0;C to ensure proper conditioning. The pelletization stage, a critical step in the process, involves mechanical manipulation to compact and bind the ingredients, ensuring the structural integrity of the final product. This stage represents the highest energy consumption within the entire production process. During the cooling process, both the temperature and humidity of the pellets are reduced, with subtle changes occurring that can affect their quality. Finally, the pellets are sifted before packaging and storage. It is anticipated that this product could have a minimum 2-month shelf life after production, although further tests are needed to accurately determine the extent of shelf stability.</p>
<fig id="f4" position="float">
<label>Figure&#xa0;4</label>
<caption>
<p>Proposal for forming moxifloxacin pellets with soy flour for administration in equines, starting with obtaining soy flour and the antibiotic. (Own elaboration using Microsoft Office PowerPoint).</p>
</caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fanim-06-1537853-g004.tif"/>
</fig>
<sec id="s7_1">
<label>7.1</label>
<title>Challenges for the inclusion of soybean meal-based moxifloxacin pellets</title>
<p>It is suggested to perform <italic>in vitro</italic> and <italic>in vivo</italic> tests to test the efficacy of this product to know its antibiotic stability, controlled release, precise dosage, and animal acceptance.</p>
<p>
<italic>Antibiotic stability</italic>: Ensuring that the antibiotic maintains its potency over the shelf life of the pellet is a crucial challenge (<xref ref-type="bibr" rid="B6">Barrueco et&#xa0;al., 2013</xref>).</p>
<p>
<italic>Controlled release</italic>: Designing pellets that release the antibiotic in a controlled and effective manner in the body can be complex. It is important that the drug is released at the right time and place to maximize its effectiveness and minimize side effects (<xref ref-type="bibr" rid="B61">Thapa et&#xa0;al., 2018</xref>).</p>
<p>
<italic>Precise dosage</italic>: Ensuring that each pellet contains a precise and consistent dose of the antibiotic is essential to ensure the effectiveness of the treatment and avoid problems of bacterial resistance (<xref ref-type="bibr" rid="B59">Sumano L&#xf3;pez et&#xa0;al., 2020</xref>).</p>
<p>
<italic>Acceptance by the animal</italic>: Pellets must be palatable to the animals that will consume them. If the antibiotic or ingredients in the pellet alter the taste or texture, the animals may reject it, which could compromise the treatment (<xref ref-type="bibr" rid="B54">Ryon et&#xa0;al., 2023</xref>).</p>
<p>
<italic>Regulation and security</italic>: Complying with safety standards and&#xa0;regulations for the use of antibiotics in animals is essential. This includes ensuring that the antibiotic levels in the pellet are safe and do not cause adverse effects (<xref ref-type="bibr" rid="B32">Loor, 2016</xref>; <xref ref-type="bibr" rid="B59">Sumano L&#xf3;pez et&#xa0;al., 2020</xref>).</p>
</sec>
</sec>
<sec id="s8" sec-type="conclusions">
<label>8</label>
<title>Conclusions</title>
<p>The development of soybean meal-based moxifloxacin pellets for equine use holds great promise, offering sustainability and the potential for more efficient drug delivery. These pellets are designed to facilitate controlled antibiotic release, which is crucial for effectively treating bacterial infections in horses. However, ensuring consistent controlled release, maintaining antibiotic stability, achieving accurate dosing, and securing animal acceptance remain significant challenges. Additionally, adhering to safety regulations is critical to prevent adverse effects and reduce the risk of bacterial resistance. Further <italic>in vitro</italic> and <italic>in vivo</italic> research is essential to overcome the obstacles and validate the viability of these granules as a safe and effective therapeutic option in veterinary medicine.</p>
</sec>
</body>
<back>
<sec id="s9" sec-type="author-contributions">
<title>Author contributions</title>
<p>DRV: Conceptualization, Writing &#x2013; original draft. JVG: Investigation, Writing &#x2013; original draft. TDA: Visualization, Writing &#x2013; original draft. DGO: Investigation, Writing &#x2013; original draft. AZMS:&#xa0;Validation, Writing &#x2013; original draft. SKR: Conceptualization, Funding acquisition, Writing &#x2013; original draft. MMMYE: Methodology, Resources, Writing &#x2013; original draft.</p>
</sec>
<sec id="s10" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research and/or publication of this article.</p>
</sec>
<sec id="s11" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s12" sec-type="ai-statement">
<title>Generative AI statement</title>
<p>The author(s) declare that no Generative AI was used in the creation of this manuscript.</p>
</sec>
<sec id="s13" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
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