Research Article

Gentamicin in Focus: A Bibliometric Exploration of Its Status as a WHO Essential Drug and Its Veterinary and Clinical Therapeutic Balance between Toxicity and Efficacy

Athraa Alzain1, Mohamed S. Ahmed2, Sherief M. Abdel-Raheem3, Mustafa Shukry1, Ibrahim Albokhadaim1, Mahmoud Kandeel1*

1Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, 31982 Al-Ahsa, Saudi Arabia; 2Department of Clinical Sciences, College of Veterinary Medicine, King Faisal University, 31982 Al-Ahsa, Saudi Arabia; 3Department of Public Health, College of Veterinary Medicine, King Faisal University, 31982 Al-Ahsa, Saudi Arabia.

Received | November 10, 2025; Accepted | February 02, 2026; Published | May 06, 2026

*Correspondence | Mahmoud Kandeel, Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, 31982 Al-Ahsa, Saudi Arabia; Email: [email protected]

Citation | Alzain A, Ahmed MS, Abdel-Raheem SM, Shukry M, Albokhadaim I, Kandeel M (2026). Gentamicin in focus: A bibliometric exploration of its status as a WHO essential drug and its veterinary and clinical therapeutic balance between toxicity and efficacy. J. Anim. Health Prod. 14(2): 780-790.

DOI | https://dx.doi.org/10.17582/journal.jahp/2026/14.2.780.790

ISSN (Online) | 2308-2801

Copyright: 2026 by the authors. Licensee ResearchersLinks Ltd, England, UK.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Introduction

Gentamicin, an aminoglycoside antibiotic first discovered in the 1940s, remains an essential therapeutic agent in the management of Gram-negative bacterial infections (Serio et al., 2018). It is considered as a cornerstone of antimicrobial therapy in both human and veterinary medicine (Abo El-Sooud, 2003; Chen et al., 2014). Gentamicin continues to be widely prescribed for systemic infections, topical applications, and in combination therapies, despite the emergence of newer antimicrobial classes (Chen et al., 2014). Its clinical importance is further underscored in resource-limited settings, where aminoglycosides remain indispensable due to their cost-effectiveness and inclusion in the World Health Organization’s List of Essential Medicines (Bārzdiņa et al., 2024; Hodiamont et al., 2022; WHO, 2025).

However, gentamicin use is constrained by well-recognized adverse effects, particularly nephrotoxicity and ototoxicity (Blunston et al., 2015). These dose- and duration-dependent toxicities have been the focus of extensive mechanistic and clinical research aimed at elucidating molecular pathways of injury and developing protective strategies (Balakumar et al., 2010). Investigations have highlighted the role of oxidative stress, apoptosis, mitochondrial dysfunction, and genetic susceptibility in mediating gentamicin-induced damage (Elgazzar et al., 2022; Ozaki et al., 2010). Clinical studies, in parallel, have sought to optimize dosing regimens, explore monitoring strategies, and evaluate adjunctive therapies to mitigate toxicity while preserving antimicrobial efficacy (Starkel et al., 2024; Sugiyama et al., 2024). The balance between therapeutic utility and toxicity risk continues to drive innovation in drug delivery systems, formulation strategies, and alternative applications such as localized release in orthopedic infections and ophthalmology (Jennings, 2015).

In recent years, gentamicin research has also expanded beyond toxicity and pharmacology into broader domains, including antimicrobial resistance and biofilm-associated infections (Nazari et al., 2024). Rising global concerns over multidrug-resistant organisms have renewed interest in aminoglycosides, both as therapeutic options and as scaffolds for novel derivatives (Zárate et al., 2018). Studies addressing gentamicin’s role in combination therapies (Ali, 2011; Li et al., 2021), its pharmacokinetics in special populations (Bos Jeannet et al., 2019), and its applications in veterinary medicine highlight the drug’s enduring relevance across disciplines (Cengiz et al., 2020).

Bibliometric analysis offers a systematic way to map scientific landscapes by tracking publication trends, influential authors and institutions, collaboration networks, and thematic shifts (Kumar, 2025). In antibiotic research, such analyses have been applied, yet no study has focused exclusively on gentamicin. Given its long clinical use, ongoing safety concerns, and expanding research scope, gentamicin is an ideal subject for bibliometric evaluation.

This study provides a comprehensive overview of global gentamicin research using Scopus database. It examines publication output, citation performance, authorship patterns, institutional and country contributions, and collaboration networks. These findings offer the first evidence-based mapping of gentamicin scholarship, highlighting major achievements, knowledge gaps, and future research opportunities.

Materials and Methods

Study design

This bibliometric study evaluated global trends, authorship patterns, institutional productivity, and thematic evolution in gentamicin-related research.

Data source and search strategy

Data were retrieved from Scopus using the query (Title (gentamicin) and Pubyear > 1994 And Pubyear < 2026 and (Limit-to (Language,”English”)) and (Limit-to (Doctype,”ar”)) and (Exclude (Prefnameauid,”undefined”))) from database inception to August 2025. To ensure consistency and quality, only English-language original research articles were included, while reviews, conference proceedings, book chapters, and other non-article publications were excluded.

Data extraction and processing

The search results were exported in CSV format with complete metadata and cited references. Extracted information included authors and co-authors, institutional affiliations, corresponding author countries, source titles, author keywords and indexed keywords, publication year, citation counts, and cited references. Data cleaning was carried out by unifying author names, standardizing institutional titles and harmonizing country identifiers.

Bibliometric indicators

The analysis considered annual publication output, citation performance through total, average, and normalized citation counts, and the identification of the most-cited papers. Authorship patterns were evaluated by examining the number of contributors, co-authorship rates, the collaboration patterns, and the share of single-authored papers. Source productivity was assessed by identifying the most active journals and their disciplinary scope, while institutional and country productivity were analyzed in terms of publication volume and degree of international co-authorship.

Collaboration analysis

International collaboration was examined through the Corresponding Author’s Country (AU_CO) field, with publications categorized as either single-country or multi-country works. A world map was generated to visualize the distribution and strength of cross-national research partnerships.

Content and thematic analysis

Content analysis was based on author and Scopus-indexed keywords to capture thematic directions in the literature. Trend topics were analyzed to follow the evolution of frequently used terms. Thematic mapping was employed to classify research themes into basic, niche, motor, or emerging and declining domains according to Callon’s centrality–density model. Thematic clustering relied on co-word analysis to group related concepts into clusters reflecting key areas such as nephrotoxicity, ototoxicity, drug delivery, and antimicrobial resistance. Thematic evolution analysis provided a longitudinal perspective on how research topics shifted and developed over time.

Tools for analysis and visualization

All analyses were conducted in R (version 4.4.1) using the bibliometrix package (version 5.1.1) and its Biblioshiny interface (Darvish, 2020). Network mapping and visualization of co-authorship, keyword clusters, and thematic structures were performed with VOSviewer (version 1.6.20) (van Eck and Waltman, 2010), and all figures were exported in high resolution for inclusion in the manuscript.

Ethical considerations

As the study relied exclusively on bibliographic metadata from Scopus without involving human participants or confidential data or animal subjects, ethical approval was not required.

Results

The dataset spans 1995–August 2025 and includes 4,727 articles from 1,687 journals. Annual growth averaged 0.49%, with papers receiving a mean of 24.6 citations. Altogether, 136,358 references were cited, alongside 18,895 Keywords Plus and 7,570 author keywords. Authorship was extensive, involving 19,283 contributors, with only 114 single-authored papers. Collaboration was strong, averaging 5.56 co-authors per article, and 15.7% of studies were internationally co-authored.

Annual scientific production

Output rose steadily over three decades. Early 2000s production remained near 100–130 articles annually, before climbing after 2010, with 178 publications in 2012 and 194 by 2016. The peak years were 2021 (225 articles) and 2022 (238). Even during the COVID-19 pandemic, output stayed high, with 198 papers in 2020. Between 2015 and 2023, annual output consistently exceeded 160 papers (Figure 1).

Most relevant sources

Antimicrobial Agents and Chemotherapy published the most articles (144), followed by the Journal of Antimicrobial Chemotherapy (96). Hearing Research (51) and Laryngoscope (47) reflected the strong ototoxicity focus, while ENT journals such as Acta Oto-Laryngologica (44) and Otology and Neurotology (36) reinforced this trend. Multidisciplinary journals like PLoS One (33) and Scientific Reports (24) contributed studies spanning pharmacology, microbiology, and toxicology. Veterinary and pharmaceutical outlets, including the International Journal of Pharmaceutics (24) and American Journal of Veterinary Research (21), highlighted applications in animal health and drug delivery (Figure 2).

 

 

Authors’ impact

Several researchers emerged as central figures. Busscher HJ and Van der Mei HC each published 20 papers with 1,812 citations, while Liu Y, López-Novoa JM and Steyger PS (16 papers). Other details can be accessed in Figure 3.

Country productivity

The USA led with 493 articles, supported by 96 international collaborations, followed by China (400) with lower international co-authorship (12.7%). Iran (229) and India (220) produced mainly domestic work. The UK (149) and Egypt (144) showed higher shares of international collaborations, while Turkey, Germany, Spain, and the Netherlands each contributed more than 100 papers (Figure 4).

 

 

Collaboration world map

The USA formed the main hub, collaborating most with China (45), Canada (25), and the UK (21). Strong bilateral ties were also seen between Egypt and Saudi Arabia (42), India and Saudi Arabia (10), and Japan and Sweden (10). European networks were dense, with Germany–Switzerland (12) and UK–Switzerland (11) being notable. Cross-continental collaborations such as USA–Japan (17) and China–Singapore (6) illustrated broad integration. (Figure 5).

Trend topics

Keyword analysis shows how gentamicin research has evolved over time. In the late 1990s, common terms included “enzymuria,” “quinolones,” and “hair cell regeneration,” indicating early exploration of toxicity markers and auditory effects. During the early 2000s, topics shifted toward “acute renal failure,” “ototoxicity,” and “free radicals,” reflecting growing attention to nephrotoxicity and oxidative stress. Between 2005 and 2015, frequent terms included “hearing loss,” “cochlea,” and “inner ear,” alongside pharmacokinetics and protective interventions such as antioxidants. After 2015, research emphasized “oxidative stress,” “antibiotics,” “nephroprotection,” and “acute kidney injury.” More recent topics include “antimicrobial resistance,” “antibiofilm,” and molecular terms like “Nrf2,” suggesting newer directions in resistance and cellular protective pathways. Veterinary and orthopedic contexts also appear, including “osteomyelitis” “rats” and “bone cement” Figure 6.

 

Most globally cited papers

The most globally cited papers span both mechanistic and clinical domains of gentamicin research. Kadurugamuwa and Beveridge (1995) leads with 567 citations, focusing on Virulence factors (Kadurugamuwa and Beveridge, 1995). Wilschanski et al. (2003) has 450 citations, representing Gentamicin-induced correction of cystic fibrosis transmembrane conductance regulator function (Wilschanski et al., 2003). Fouhy et al. (2012) achieved 419 citations, highlighting microbiome changes associated with antibiotic use in infants (Fouhy et al., 2012). Other highly cited works include Doadrio et al. (2004) with 366 citations, emphasizing drug delivery systems (Doadrio et al., 2004), and Yoshizawa et al. (1998) with 327 citations on gentamicin antimicrobial mechanisms (Yoshizawa et al., 1998). Additional highly cited contributions include Lucke et al. (2003) with 298 citations and Priuska and Schacht (1995) with 298 citations, both focusing on bone-related applications and pharmacological insights (Lucke et al., 2003; Priuska and Schacht, 1995). Abdelbary and El-Gendy (2008) (292 citations) highlighted ophthalmic

 

Table 1: Most globally cited papers with topics, TC: total citations.

Paper	DOI	Total citations	TC per year	Normalized TC	Topic
Kadurugamuwa JL, 1995	10.1128/jb.177.14.3998-4008.1995	567	18.29	17.90	Virulence factors
Wilschanski M, 2003	10.1056/NEJMoa022170	450	19.57	8.96	CFTR correction in cystic fibrosis
Fouhy F, 2012	10.1128/AAC.00789-12	419	29.93	12.76	Microbiome changes in infants
Doadrio AL, 2004	10.1016/j.jconrel.2004.03.005	366	16.64	8.55	Drug delivery systems
Yoshizawa S, 1998	10.1093/emboj/17.22.6437	327	11.68	12.77	Ribosomal mechanisms
Lucke M, 2003	10.1016/S8756-3282(03)00050-4	298	12.96	5.93	Bone-related applications
Priuska EM, 1995	10.1016/0006-2952(95)02160-4	298	9.61	9.41	Pharmacological insights
Abdelbary G, 2008	10.1208/s12249-008-9105-1	292	16.22	8.13	Ophthalmic controlled delivery
LaPlante KL, 2004	10.1128/AAC.48.12.4665-4672.2004	278	12.64	6.49	Antimicrobial efficacy
Fernández-Hidalgo, 2013	10.1093/cid/cit052	273	21.00	10.47	Infective endocarditis
Zhou Y, 2008	10.1093/toxsci/kfm260	273	15.17	7.60	Nephrotoxicity and toxicity mechanisms

 

 

controlled delivery (Abdelbary and El-Gendy, 2008), while LaPlante and Rybak (2004) (278 citations) investigated antimicrobial efficacy (LaPlante and Rybak, 2004). Fernández-Hidalgo et al. (2013) (273 citations) provided influential evidence on infective endocarditis (Fernández-Hidalgo et al., 2013). Studies addressing toxicity, such as Zhou et al. (2008) (273 citations), show sustained impact (Zhou et al., 2008) (Table 1).

Interconnections of countries, institutions, journals, and research themes in gentamicin research

Gentamicin research demonstrates a wide international footprint (AU_CO), with the USA and China producing the highest outputs, supported by significant contributions from Iran, India, and Egypt. These countries reflect both high-resource settings with advanced biomedical infrastructure and regions where aminoglycosides remain widely used in clinical practice. Prominent institutions (AU_UN) driving this scholarship include the King Saud University and Oregon Health and Science University. Their research portfolios link strongly to ototoxicity and nephrotoxicity, two of the most critical adverse effects of gentamicin, while also addressing antimicrobial resistance and pharmacological innovations (Figure 7A).

Publication venues (SO) with the greatest output such as Laryngoscope, Otology and Neurotology, Hearing Research, Antimicrobial Agents and Chemotherapy, Life Sciences, and Renal Failure mirror the dual research focus on auditory and renal systems. Keyword analysis (DE) highlights the dominance of “gentamicin” alongside “ototoxicity,” “nephrotoxicity,” “aminoglycosides,” “oxidative stress,” and “apoptosis,” underscoring the mechanistic exploration of toxicity. Terms like “vertigo” and “pharmacokinetics” indicate specialized attention to inner ear physiology and drug metabolism, showing how research themes bridge molecular pathways, clinical management, and therapeutic safety (Figure 7B).

Core, niche, and emerging themes in gentamicin research

The thematic map provides a structured overview of gentamicin research by organizing topics according to their centrality and density. In the basic themes quadrant (high centrality, low density), “gentamicin,” “nephrotoxicity,” and “ototoxicity” dominate, underscoring their role as foundational areas of study that shape the field’s core. Interestingly, the motor themes quadrant

 

 

(high centrality, high density) is empty, indicating a lack of strongly developed and simultaneously evolving cutting-edge topics. Niche themes (high density, low centrality include “vertigo,” “Ménière’s disease,” and “hearing loss,” reflecting specialized audiological investigations that are well-established but not central to the wider field. At the map’s intersection, transversal topics such as “gentamicin sulfate,” “drug delivery,” and “antibacterial activity” appear, linking across domains and bridging core, niche, and emerging research areas (Figure 8).

Thematic clustering and evolution

The green cluster centers on gentamicin and aminoglycosides, linking closely to infection, Pseudomonas aeruginosa, and antibiotic resistance. The red cluster emphasizes drug delivery, including gentamicin sulfate, osteomyelitis, chitosan, hydroxyapatite, and liposomes, highlighting biomedical engineering approaches. The blue cluster focuses on nephrotoxicity with terms like acute renal failure, oxidative stress, and inflammation, while the yellow cluster addresses ototoxicity through keywords such as hearing loss, cochlea, hair cells, and vertigo. A smaller purple cluster relates to pharmacokinetics and neonatology, featuring neonatal sepsis and therapeutic drug monitoring (Figure 9A).

 

Older topics, shaded in purple and blue, include “ototoxicity,” “hearing loss,” and “intratympanic gentamicin,” reflecting early focus on auditory side effects. Central terms such as “gentamicin,” “aminoglycosides,” “infection,” and “Pseudomonas aeruginosa” appear in green, indicating their sustained relevance over time. More recent themes, shown in yellow, include “nephrotoxicity,” “oxidative stress,” “hepatotoxicity,” and “antioxidant,” highlighting growing interest in toxicological mechanisms. Drug delivery systems, with terms like “gentamicin sulfate,” “chitosan,” and “hydroxyapatite,” also shift toward green and yellow, marking their increasing prominence in the literature (Figure 9B).

Discussion

Our comprehensive bibliometric analysis reveals that gentamicin research has maintained remarkable vitality and relevance over three decades, with annual growth averaging 0.49% and consistent output exceeding 160 papers between 2015-2023. This sustained productivity reflects gentamicin’s enduring clinical importance, particularly in an era where antibiotic resistance threatens global health security (Salam et al., 2023). The United States’ leadership with 493 publications, followed closely by China’s 400 contributions, mirrors the global distribution of advanced biomedical research infrastructure and clinical expertise. Interestingly, the strong representation from Iran, India, and Egypt underscores gentamicin’s continued relevance in resource-limited settings where aminoglycosides remain first-line therapeutic options due to their cost-effectiveness and inclusion in essential medicine lists (Gupta, 2022; WHO, 2025).

The predominance of Antimicrobial Agents and Chemotherapy and the Journal of Antimicrobial Chemotherapy as leading publication venues reflects the field’s core focus on antimicrobial efficacy and resistance mechanisms. However, the substantial presence of otolaryngology journals such as Hearing Research and Laryngoscope illuminates both a cause of and treatment of inner ear disorders (Fogliano et al., 2022). This duality exemplifies the complex relationship between therapeutic benefit and adverse effects that has driven gentamicin research for decades.

The evolution of research themes from early “enzymuria” and “quinolones” studies to contemporary focuses on “oxidative stress,” “Nrf2 pathways,” and “antimicrobial resistance” reflect both methodological advances and shifting clinical priorities. The emergence of molecular protective mechanisms and biofilm research indicate that gentamicin serves as a valuable model for understanding antibiotic action on bacteria (Nazari et al., 2024; Sekar et al., 2024).

When compared to other antibiotic bibliometric studies, our findings reveal unique characteristics specific to gentamicin research. While penicillin and fluoroquinolone bibliometric analyses typically show stronger industrial pharmaceutical contributions (Arshad et al., 2020; Dagli et al., 2024; Gómez-Ríos and Ramirez-Malule, 2019), gentamicin research demonstrates a more academically-driven pattern with significant institutional diversity across developing nations. This contrasts sharply with vancomycin bibliometric studies, which show heavier concentration in high-resource settings (Minotti et al., 2021). Previous aminoglycoside bibliometric work by Zhao et al. (2025) found similar toxicity-focused (Zhao et al., 2025). The sustained growth pattern we observed differs from the exponential growth seen in antibiotic resistance bibliometrics, indicating gentamicin’s mature but stable research pattern.

Our findings carry profound implications for both research prioritization and clinical practice. The thematic clustering analysis reveals that while nephrotoxicity and ototoxicity remain foundational research areas, the field is enriched by antimicrobial resistance concerns and novel drug delivery technologies.

Our study demonstrates several notable strengths, including comprehensive coverage spanning three decades of research with rigorous methodology using established bibliometric tools and databases. The multidimensional analysis incorporating publication trends, collaboration patterns, and thematic evolution provides a holistic view of the field’s development.

However, several limitations warrant consideration. The exclusive reliance on Scopus database may have underrepresented journals not indexed in this platform. Our focus on English-language publications likely excluded valuable research published in other languages, particularly from non-English speaking countries with strong gentamicin research programs. Additionally, the static nature of bibliometric analysis cannot fully capture the dynamic, real-time evolution of research priorities or emerging methodological innovations.

Conclusion

This bibliometric analysis reveals gentamicin research as a dynamic, globally distributed field successfully balancing fundamental toxicological investigations with innovative therapeutic applications. The sustained research interest, strong international collaborations, and thematic diversification position gentamicin to address emerging challenges in antibiotic resistance and clinical medicine. It is recommended to increase the investment in international collaborative networks, particularly between high-resource and developing nations where gentamicin remains clinically essential.

Acknowledgments

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. KFU254012).

Novelty Statement

This study presents the first bibliometric mapping of gentamicin research. The study analyzed publication trends and thematic evolution over three decades. It highlights the shifting balance between toxicity, antimicrobial resistance, and therapeutic innovations across both humans and veterinary domains.

Author’s Contribution

AA, MSA, SMA, MS, IA, MK: Conceptualization. AA, MSA, MK: Data curation. SM, SMA, MS, IA: Formal analysis. MSA: Funding acquisition. MK: Methodology. IA: Project administration. MK: Resources. MK: Software.

MK: Writing original draft. AA, MSA, SMA, MS, IA: Writing review and editing.

Funding

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. KFU254012).

Ethical approval

Not applicable.

Informed consent statement

Not applicable.

Data

Data can be requested from the corresponding author upon reasonable request.

Generative AI and AI-assisted technology statement

Artificial intelligence tools were used only for grammar correction and sentence editing. The authors affirm that all scientific content, data analysis, interpretations, and conclusions are solely their own.

Conflict of interest

The authors have declared no conflict of interest.

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