A Bibliometric Perspective on Tylosin Research: Scientific Development and Emerging Trends Over Six Decades

Tylosin is a macrolide antibiotic that is naturally produced by Streptomyces fradiae. It has been widely used in veterinary medicine (Gingerich et al., 1977; Liu and Douthwaite, 2002). Tylosin is used primarily for the treatment of bacterial infections in livestock and poultry (Liu and Douthwaite, 2002). To date, it remains one of the most commonly used veterinary antibiotics in the world, especially in beef cattle and swine production and poultry systems (Cazer et al., 2020; De Liguoro et al., 2003; Liu and Douthwaite, 2002). Its primary applications include treatment of respiratory diseases (Borang et al., 2023), and control of enteric diseases e.g., swine dysentery (Wallgren, 2024).

In addition to its therapeutic applications, tylosin was also used as a growth promoter in livestock animals, although some regulatory bodies began to impose restrictions on this practice in the last decades of the 20^th century, related to environmental pollution and potential for emergence of drug resistance (Cazer et al., 2020; Mithuna et al., 2024). The application of tylosin as a veterinary antibiotic has generated considerable interest in the scientific community through interdisciplinary approaches. From a veterinary medicine perspective, researchers have extensively studied the pharmacokinetics, therapeutic applications, safety and dosage protocols for a wide variety of pathogens and animal species (Cybulski et al., 2025; Lee et al., 2024; Ronaghinia et al., 2021). From an environmental perspective, the fate and transport of tylosin residues in soil, water and manure-amended agricultural systems have been addressed, considering that a large proportion of the antibiotics administered to livestock is excreted into the environment with little or no metabolic alterations (Kunz et al., 2025; Loke et al., 2000). From a food safety perspective, researchers have developed analytical methodologies for the detection and quantitation of tylosin residues in animal-derived foods such as meat, milk and honey, and adherence to maximum residue limits defined in regulations is controlled to ensure consumer safety (Gürel Yücel et al., 2023).

Tylosin has the same binding site and mode of action as the human macrolides, binding to the 50S ribosomal subunit and inhibiting bacterial protein synthesis via interaction with 23S rRNA (Cattoir and Leclercq, 2017). Tylosin resistance can be mediated by methylation of the A2058, which affects the binding pocket of clinically important macrolides (Cattoir and Leclercq, 2017). Application of tylosin could therefore lead to selection of cross-resistance, resulting in reduced sensitivity to both tylosin and other macrolides. The common ribosomal binding site for tylosin and macrolides used in human medicine provides a clear molecular mechanism to explain cross-resistance due to the application of veterinary tylosin. This One Health context warrants further investigation.

Macrolides contain a macrolide lactone ring with 12-, 14-, 15-, or 16-membered rings, with different amino and neutral sugars and side-chain substitutions. These variations influence ribosome interactions, membrane permeability, pharmacokinetics, and susceptibility to various resistance mechanisms (Li et al., 2023; Nor Amdan et al., 2024). Azithromycin, for example, is a 15-membered azalide derived from 14-membered erythromycin but has an additional nitrogen in the macrolide ring (Nor Amdan et al., 2024). Several veterinary macrolides, such as tylosin, spiramycin, and midecamycin, are 16-membered with different substitutions (Nor Amdan et al., 2024). These structural peculiarities might account for binding differences that result in different resistance patterns to certain macrolide drugs (Nor Amdan et al., 2024). A recent study, however, showed that the ring structure of macrolides affects certain resistance determinants (Singh et al., 2025). In Salmonella, for example, certain resistance determinants conferred different resistance to 14-, 15-, and 16-membered macrolides. 23S rRNA mutations in Campylobacter resulted in significantly elevated MICs to all macrolides (Singh et al., 2025). Therefore, macrolides are cross-resistant to one another to some extent, and a One Health perspective on resistance selection and spread due to macrolide use is a major concern. The concern is that using a distinct class of macrolides in food-producing animals might select for resistance genes that are used in human macrolides.

However, no bibliometric analysis has been performed to date to provide a systematic overview of the research trends on tylosin based on the vast pool of available literature. Bibliometric analysis is a quantitative research method used to examine publication and citation patterns, collaboration networks, and thematic trends and evolution across scientific disciplines (Donthu et al., 2021). It provides valuable insights into knowledge construction and identifies the most influential factors, emerging research areas, and gaps in a particular research domain that require further exploration.

This study aimed to: (i) assess annual publication trends and leading journals; (ii) identify productive authors and institutions; (iii) determine and analyze the most highly cited studies; (iv) examine global authorship and international collaboration; (v) trace major research trends over time; (vi) map relationships among countries, institutions, sources, and topics; (vii) classify core, niche, and emerging themes; and (viii) evaluate thematic clusters and their evolution. For this purpose, we retrieved article data from Scopus, a multidisciplinary database with broad coverage, high-quality indexing, and comprehensive citation reporting, making it one of the most appropriate bibliographic databases for bibliometric studies.

The bibliometric analysis of research on tylosin was undertaken using the Scopus database. It was searched to cover all publications on the subject from inception till August 2025. Only English-language articles were included, and the dataset was restricted to research articles to ensure methodological coherence. The search query included (Title (tylosin) and (Limit-To (Language,”English”)) AND (Limit-To (Doctype,”ar”))). Scopus was selected as the sole data source because of its broad multidisciplinary coverage, standardized citation metadata, and compatibility with bibliometric analysis tools, ensuring a consistent dataset without cross-database duplication.

Bibliometric metadata such as title, authors, corresponding author’s institutional address, country, year of publication, journal name, citation count, keywords, and references were extracted. At the author level, information regarding the number of publications, institutions, co-authors, etc., was systematically obtained for the analysis of productivity and collaboration.

To facilitate a comprehensive analysis, primary bibliometric parameters were computed, such as the annual research output, mean document age, mean citation per article, co-authorship rate and international collaboration. Publications were classified as single-country publications (SCP) and multi-country publications (MCP) to capture global collaborative effort. The total number of publications at the author-level, fractional contribution, and weighted metrics were generated.

Keyword analysis was performed to identify the centrality and density values of the motor, niche, basic, and rising/declining research topics. Trend analysis recognized the sequence of top topics that appeared over time, such as pharmacokinetics, antimicrobial resistance, environmental fate and behavior, and analytical methods. Journals, institutions, and countries were studied to evaluate comparative productivity and collaboration.

Bibliometric analysis and network visualization were performed through the Bibliometrix version 5.4.1 in R package and VOSviewer(version 1.6.20), respectively (Darvish, 2019; van Eck and Waltman, 2010).

The bibliometric dataset encompassed 899 tylosin-related articles published between 1960 and 2025, derived from 389 distinct sources, with an annual growth rate of 4.87%. The 2025 records covered the range January–August at the time of search, which was included in the annual growth-rate calculation. The literature exhibited a document average age of 21.5 years and a mean of 23.85 citations per article (Table 1).

Table 1: Summary characteristics of the research articles on tylosin published from 1960 to 2025.

The scientific trajectory of tylosin-related research has been marked by a stable record over the last 65 years, starting with one publication in 1960 and slowly gaining pace through the years. A relatively low number in the 1960s and 1970s; a higher pace was observed during the 1980s and 1990s. However, from the end of the 1990s and the beginning of the 2000s, the number of publications per year surpassed 20. The last years marked surge, with 2024 having 38 publications and 2022–2023 with 33–36 articles each (Figure 1).

The top author of the publications is Cundliffe with 24 publications. Currently active researchers from China are Wang Y (19 articles), Guo X (18), and Li Y (16), who are major players among others (Figure 2).

Kansas State University has the highest volume of output at 86 publications. The other key institutions in China are Northeast Agricultural University (66 publications), South China Agricultural University (65 publications) and Huazhong Agricultural University (46 publications). University of Leicester (51 publications) and Northwest A&F University (31 publications) (Figure 3).

Rabølle and Spliid (2000), with 401 total citations, tested tylosin’s sorption and mobility in soil (Rabølle and Spliid, 2000). Guo et al. (2018), with 378 citations, examined tylosin sorption on microplastics, addressing emerging pollutant interactions (Guo et al., 2018). Keatinge-Clay (2007) explained that ketoreductase domains control chirality in polyketide synthesis (Keatinge-Clay, 2007). De Liguoro et al. (2003, 272 citations) evaluated tylosin transfer from intensive calf farming to manure and soil (De Liguoro et al., 2003). Dong et al. (2018, 265 citations) synthesized g‑C₃N₄ via a burning explosion method and the photocatalytic degradation of tylosin (Dong et al., 2018). Kim et al. (2012, 216 citations) showed that tylosin as a growth promoter caused microbial population shifts in swine gut microbiomes (Kim et al., 2012). Ter Laak (2006, 210 citations) investigated the effect of pH and ionic strength on soil sorption of tylosin (ter Laak et al., 2006). Loke et al. (2002, 199 citations) characterized tylosin distribution coefficient in manure (Loke et al., 2002). Finally, Aust et al. (2008, 191 citations) [9] studied tylosin distribution in Canadian feedlot manure and soil (Aust et al., 2008) (Table 2).

The United States has the highest publication frequency, followed by China. These two countries dominate in research production. Japan is third, followed by the United Kingdom (Figure 5).

For corresponding authors’ countries, China leads the list with 140 contributions, including 121 as SCP and 19 MCP. The USA has 126 contributions, including 112 SCP and 14 MCP. Other significant contributors include Korea (21), the United Kingdom (21), and Canada (20) (Figure 5).

The early period (1996-2002) was characterized by a microbiology focus. Characterization of Streptomyces fradiae (28 papers, median year of appearance 1998) and optimization of tylosin production (9 papers) were the most important topics. The next period (2002-2010) showed enrichment of research themes by pharmacokinetics

Table 2: The most highly cited tylosin-related articles ranked by total citations, with their publication details, DOI, annual citation rate, and normalized citation score (TC, total citations). Normalized TC was calculated by dividing the total citations received by each article by the mean total citations of all articles published in the same year.

and environmental factors, as well as the growing importance of some research topics such as macrolide (14 papers), methods for the detection of drug residues in food matrices, such as honey (13 papers, median year of appearance 2007), and evaluation of drug stability in different conditions. The most recent third period (2014-2024) is characterized by a clear reorientation of research to environmental degradation and resistance issues. It concerns first and foremost the drug itself (total number of papers on tylosin 323, median year of appearance 2014). As for the latter, it concerns drug degradation (12 papers, median year of appearance 2014), adsorption (16 papers, median year of appearance 2020), photocatalytic decomposition (9 papers, median year of appearance 2023), antibiotic resistance genes (6 papers, median year of appearance 2021) (Figure 6).

The co-occurrence analysis of tylosin data showed the interconnectedness of countries, institutions, and research themes. China was the dominant country, followed by the USA. The leading institutions were Northeast Agricultural University, Kansas State University, and Huazhong Agricultural University. The research focus of tylosin as an emergent term was further explored and expanded into the fields of veterinary medicine (liver abscesses, tilmicosin), microbiology (Streptomyces fradiae, antimicrobial resistance), livestock industry (swine, cattle) and pharmacology (pharmacokinetics, residues). In terms of the publication patterns, the prominent journals were identified, such as Journal of Animal Science, Chemosphere, and Applied Animal Science. Keywords provided crucial insights into the prominent research themes in the tylosin domain, including environmental issues (degradation, sorption, adsorption), food safety (residues, honey, milk), and therapeutic uses, confirming that the tylosin research is highly interdisciplinary and involves well-established collaborations among institutions (Figure 7).

The thematic map organizes the tylosin research themes based on development and centrality. The motor themes (top right), such as macrolides, swine, and antibiotic resistance, are the most developed and central themes in the research and are the main topics in the field to which the others are linked. The basic themes (bottom right) as liver abscesses, cattle, pharmacokinetics, and Streptomyces fradiae are connected to the basic themes and are relevant, but less developed. The niche themes (top left), such as copper biochar, nano-hydroxyapatite, and photocatalytic applications, correspond to the most developed and specialized research themes but are found in a peripheral position. Finally, the emerging or declining themes (bottom left) as tylosin production, glycosyltransferase, kinetics, and biodegradation (Figure 8).

The keyword co-occurrence network indicates the presence of different research themes or clusters in the research done on tylosin. We can distinguish several research clusters, which include the veterinary cluster (swine, cattle, liver abscess, monensin), the environmental fate cluster (sorption, adsorption, degradation, biochar, photocatalytic), the analytical methods cluster (HPLC, pharmacokinetics, ELISA, validation), food safety cluster (milk, honey, residue), and related antibiotics cluster (tetracycline, oxytetracycline, macrolides, tilmicosin).

Temporal analysis shows the evolution of publications. In the first stage of research (blue nodes), studies were about classical veterinary uses, such as treatments for livestock. In the second stage (green, 2010-2015), investigations were centered on processes related to the environmental fate and development of analytical methods. Finally, in the last period of research (yellow), publications focused on new topics that received due attention, such as antibiotic resistance genes, technologies for environmental remediation (photocatalysis, biochar), residue monitoring in food, etc. (Figure 9).

Based on this bibliometric study, the findings and perspectives from 899 publications in this 65-year research field reveal a comprehensive transformation process. The field maintains an annual growth of 4.87%. This is not only academic growth but also an evolution in the understanding that veterinary antibiotics are part of complex, interlinked systems whose impacts extend to animal well-being, environmental health, and human welfare. The increasing number of publications after 2000, 38 articles for the 2024 estimate, correlates with the onset of a decisive stage of perception of antibiotic resistance not as a clinical probability issue. It reflects global cooperation in deserving a multidisciplinary approach of top priority (Muteeb et al., 2023). Among the high-impact papers, interest focuses on the degradation of tylosin and the environmental fate and impacts (Guo et al., 2018; Rabølle and Spliid, 2000; Wang et al., 2025).

The implications of our results are consistent with other recent bibliometric studies. Sweileh and Moh’d Mansour (2020) surveyed 2,611 articles on antimicrobial resistance in the environment (2000–2019) from the SciVerse Scopus database and reported an average of 22 citations per document and more than 600% increase in publications between 2011–2019 (Sweileh and Moh’d Mansour, 2020). Our average of 23.85 citations per article is similar, and both studies listed resistance detection as top research themes. Zheng et al. (2022) analyzed articles during the period of 1946–2016 from Web of Science about antibiotics in the soil and reported that the USA and China are top contributors to research on antibiotics in soil, tetracycline was the most-studied antibiotic, and research focuses on resistance bacteria, genes, interactions/fate in soil and transport (Zheng et al., 2022). Similarly, they listed leading research themes for tylosin as resistance bacteria, environmental interactions/fate, transport and remediation. Sun et al. (2022) determined that top contributors to antibiotic research from 2010 to 2020, as retrieved from the Web of Science, were the Chinese Academy of Sciences and the journal Science of the Total Environment (Sun et al., 2022). In our study, top research contributors were Kansas State University, Northeast Agricultural University and the journal Chemosphere. This demonstrates that environmental journals and research institutes are leading contributors to antibiotics research. Evolving pathways, such as photocatalysis for tylosin remediation, are paralleled in studies of nanomaterials for antimicrobial research. Ashraf et al. (2023) studied antibiotics and pharmaceuticals in the environment from 1996 to 2020 and listed theme clusters that correspond to clusters for tylosin research in veterinary medicine, environmental fate, analytical methods, and food safety (Ashraf et al., 2023).

The implications of the thematic development from our analysis resonate with the various stakeholders in the veterinary pharmaceutical landscape. Regulatory policy should take notice of the paradigm shift from production-related research to the emphasis on environmental fate and resistance mechanisms. Therefore, environmental risk assessment can be applied in an integrated manner - one that considers the long-term impact of antibiotic agents not only on therapeutic efficacy, but on ecological variables as well. Furthermore, the widespread emergence of photocatalytic degradation and advanced oxidation research in the most recent years offers technological promise for the reduction of the environmental stability of tylosin, which may in turn be used to inform breakthroughs in wastewater treatments for livestock facilities (Rasoulifard et al., 2012; Wang et al., 2025).

The major contribution of this study is its breadth of coverage over time. Its robust bibliometric focus allows researchers to glean insights from 65 years of tylosin-related research efforts. The study considered articles in multiple fields, patterns of authorship, institutional collaboration, thematic shifts, and citation impact. In terms of limitations, reliance on the Scopus database and the restriction to research-related articles in English constrained overall coverage of the relevant literature across multiple databases and languages.

This bibliometric analysis illustrates the evolution of tylosin research from its pharmaceutical uses as a veterinary antibiotic to complex socio-ecological concerns. The growing body of evidence over the years highlights the positive impact of tylosin in chemotherapy and the negative effects on the environment and the spread of resistance. This renders the One Health concept of antibiotic resistance applicable, though not prescribed in humans, mediated by the conserved binding site on the 50S ribosomal subunit, cross-resistance to important medical macrolides, and facilitated by entry into humans via animal-based food sources. In this sense, the proposed research priorities should consolidate knowledge and advance functional applications and rigorous design principles at the One Health level. International collaboration should be strengthened through enhanced intersectoral engagement and improved predictive and analytical tools through monitoring and environmental aspects. Echoed across the identified subject clusters, themes of antimicrobial resistance, residues, decay, and release into the environment illustrate the need for strengthened surveillance of resistance and contamination in relevant sectors, monitoring of residues along the food chain, and environmentally sustainable remediation methods. Beyond these, the relatively limited apparent international collaboration and the ongoing prominence of pharmacokinetic and veterinary application studies call for highly collaborative efforts and broad-scale coordination between countries in developing formulations, targeting, delivery, and regulatory frameworks.

We appreciate the financial support from the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Grant No. KFU260703).

Despite tylosin’s important applications, little is known about the existing scholarly output on its use. This is the first bibliometric study that examines the past, present, and future trajectories of tylosin research. This study provides an extensive bibliometric analysis of research themes, international collaborations, trends, publication counts, and citations on the application of tylosin, as well as a research roadmap within a One Health concept. The study also identifies established and emerging specialized themes, as well as those that have declined in popularity.

Conceptualization: RN, YK, MM, AK, MK. Data curation: MM, MK. Formal analysis: RN, AK, YK. Funding acquisition, methodology, resources, software and writing original draft: MK. Investigation, project administration: YK. Writing review and editing: RN, YK, MM, AK.

This work was supported by the Deanship of Scientific Research, Vice Presidency for Graduate Studies and Scientific Research, King Faisal University, Saudi Arabia (Grant No. KFU260703).

The authors declare that no generative AI and AI assisted technology was used in the creation of this manuscript.

The authors have declared no conflict of interest.