Acinetobacter baumannii is an important Gram-negative pathogenic bacterium that is widespread in nature (Pandey et al., 2022). It can cause a variety of infections including meningitis, endocarditis, ventilator-associated pneumonia in intensive care, urinary tract infections and bacteremia (Antunes et al., 2014; Li et al., 2023). Study showed that the six leading pathogens for deaths associated with resistance were responsible for 929,000 deaths attributable to Antimicrobial resistance (AMR) and 3.57 million deaths associated with AMR in 2019, and that A. baumannii is one of them (Antimicrobial Resistance Collaborators, 2022). Furthermore, A. baumannii has demonstrated a remarkable ability to rapidly evolve resistance to conventional antibiotics, leading to the emergence of multidrug-resistant A. baumannii (MDRAB), extensively drug-resistant A. baumannii (XDRAB) and pan-resistant A. baumannii (PDRAB) strains. In particular, carbapenem-resistant A. baumannii (CRAB) is on the World Health Organization (WHO) list of critical priority bacteria for which new antimicrobial strategies are urgently needed (Tacconelli et al., 2018). As current antibiotics are becoming ineffective and there are still some challenges in the discovery and synthesis of new antibiotics, much effort has been directed towards the development of new therapeutic options to combat AMR, including phage or phage therapeutics, phage-encoded products, etc. (Chang et al., 2022). As of today the application of phages as antimicrobial agents has received increasing attention as a promising and safe therapeutic supplement for the treatment of bacterial infections (Nale and Clokie, 2021; Satta et al., 2022).

Phages are the most abundant and ubiquitous organisms on Earth and play important roles in microbial physiology, population dynamics, evolution and therapy (Clokie et al., 2011). Specifically speaking, because they are viruses, phages can target and kill their specific host bacteria, including antibiotic-resistant strains. Phages with a forced lysis life cycle are used in phage therapy, where they inject their genetic material into host bacteria, replicate themselves and then release their progeny through lysis. Unlike antibiotics, phages have high host specificity and low intrinsic virulence, minimizing interference with normal flora (Chang et al., 2020; Chang et al., 2022; Chang et al., 2018; Chang et al., 2017). Since the early 1920s, phages have been considered as therapeutic agents due to their unique antimicrobial capacity. Phages are considered to be one of the most promising alternatives to conventional antibiotics due to their high antibacterial capacity, large number (10³⁰ ~ 10³² in the earth), low toxicity and side effects to humans (Hibstu et al., 2022; Tu et al., 2023; Uyttebroek et al., 2022).

Phage therapy relies on the precise use of phages to attack and kill bacteria and effectively control infections (Abedon et al., 2011). Since the first report of the protective effect of phage BS46 on mice infected with A. baumannii strain AC54 (Soothill, 1992), more and more phages have been identified for lysing A. baumannii, and some phages have even shown promising antimicrobial properties in animal models (Wang et al., 2023). In addition to live phages, some phage-derived enzymes, such as intracellular lysins and depolymerases, have been shown to possess bactericidal activity (Chen et al., 2022; Chu et al., 2022). Furthermore, the efficacy and safety of phage therapy has been demonstrated (Zhang et al., 2022). Case reports of pneumonia (Cha et al., 2018), wound infections (Regeimbal et al., 2016), bacteraemia (Leshkasheli et al., 2019) and sepsis (Jasim et al., 2018), as well as phage therapy targeting patients with a variety of diseases that are carbapenem-resistant or MDRAB demonstrate the potential value of phage therapy in clinical practice (Schooley et al., 2017; Tan et al., 2021; Wu N. et al., 2021). The most common phage therapies currently used against A. baumannii include single phage therapies (McCallin et al., 2018), phage mixtures (Molina et al., 2021), phage-antibiotic combination therapies (Luong et al., 2020b), and novel phage therapies such as phage-derived enzymes (Oliveira et al., 2018) and photosensitizer combination therapies (Ran et al., 2020; Zhang et al., 2022). Phage therapy has also been reported as a promising alternative to address the ongoing problem of A. baumannii biofilm infections (Teymouri et al., 2024).

Bibliometric analysis is a statistical method based on public literature databases that allows for quantitative and qualitative evaluation of publications to assist in analyzing research hotspots and trends in specific fields (Zhang et al., 2020). To the best of our knowledge, no bibliometric analysis have been published on the use of phages in A. baumannii infections. In this study, we aimed to use quantitative methods to analysis the application of phages in A. baumannii infections, to identify the main contributors and the current state of research in this field, and to suggest future research trends.

To the best of our knowledge, this is the first bibliometric analysis of the literature related to the use of phages in A. baumannii infections. Considering the sparse number of relevant studies prior to 2010, and the fact that these studies were scattered and spanned a wide range of time, even one of them lacked abstract, it was therefore not appropriate to include these studies in this review. Consequently, for the present study, 264 studies created between 1 January 2010 and 22 February 2025, that met the inclusion criteria were selected and analyzed by multiple software tools. This analysis generated tables and visual graphs to reveal the current state of research, popular research topics and cutting-edge trends in the field.

Overall, the number of annual publications in the field fluctuates back and forth, but the general trend is one of gradual increase. The number of publications peaks in 2024. The year 2019 was an important year for the field as it had the highest H-index and has remained high in subsequent years. We then analyzed the most influential countries, institutions, authors and journals in the field. China was found to be the leader in the field, with 3.65 times more publications than the second-ranked country, which is reflected in the fact that China has the highest number of international partnerships, publications, citations, and the highest H-index, with 4 of the 10 most cited studies coming from China. In addition, Tzu Chi University and Lin, Nien-Tsung are the most influential institutions and authors in this field in terms of H-index. In addition, Frontiers in Microbiology, Viruses-Basel, and Scientific Reports are considered to be the top three most influential journals in this field. Frontiers in Microbiology has the highest H-index, while Viruses-Basel has the highest number of publications. In terms of citations, Antimicrobial Agents and Chemotherapy has the highest total number of citations and the highest average number of citations per paper.

The reason for leading in research output, especially at the national level, in the case of China, the significant share of publication may also be related to the relevant policy promotion, in addition to the necessary resource input. In 2022, China’s National Health and Health Commission formulated the National Action Plan for Containment of Microbial Resistance (2022–2025), which is a follow-up to the implementation of the previous version of the plan (2016–2020) (Yuetian and Wenjuan, 2024), it can be affirmed that China has achieved some success in AMR, such as the 2023 version of the published Guidelines for the Diagnosis, Treatment, Prevention and Control of Carbapenem-Resistant Gram-Negative Bacterial Infections (Zeng et al., 2023), but the overall resistance situation is still not optimistic. 2022 China antimicrobial resistance surveillance system (CARSS) bacterial drug resistance surveillance report (Yuetian and Wenjuan, 2024) showed that the detection rate of CRAB was as high as 53.4%. In the same year, the Centers for Disease Control and Prevention (CDC, United States) published a report on the impact of novel coronavirus infections on AMR, which indicated a significant increase in the incidence of infections caused by healthcare-associated drug-resistant pathogens, with a 78% increase in the detection rate of Centers for Disease Control and Prevention (2023), therefore, it is imperative to strengthen the scientific research and cooperation on microbial resistance prevention and control in the world.

We then analyzed the top 10 most cited studies in the field. Highly cited studies are usually considered to be important and influential. One of the most cited publications reported a clinical case study of phage therapy for drug-resistant A. baumannii infections (Schooley et al., 2017), successfully applied personalized phage therapy to effectively eradicate drug-resistant A. baumannii infections by intravenous and local injection of a phage cocktail. Another similar clinical case study among these 10 studies (LaVergne et al., 2018), which reported the case of a patient with multidrug-resistant A. baumannii infections treated with intravenous phage therapy after craniectomy. Although the patient did not recover from the injury, phage therapy was well tolerated with no significant adverse effects. The therapeutic experience with phages is encouraging, good clinical outcomes have been observed and the safety profile appears to be positive, but there are still few clinical trials of phage therapy for A. baumannii infections. There is clearly an urgent need for more clinical trials to confirm the value of phage therapy on the basis of evidence-based medicine.

In addition, 4 studies characterized the antimicrobial properties of different phages. One of them (Gordillo Altamirano et al., 2021) characterized phages ΦFG02 and ΦCO01. To exert their antimicrobial effects by targeting the capsule of A. baumannii, and the resistant mutant strains were re-susceptible to various antimicrobial agents due to the absence of the capsule, and the phage therapies showed significant antimicrobial effects in a mouse model. Researchers in another study (Yang et al., 2010) isolated and characterized the phage AB1, a potent phage of A. baumannii, which exhibited rapid growth and high pH stability and high thermal stability. The third study (Lin et al., 2010) characterized the virulent A. baumannii phage fAB2 isolated from hospital wastewater for the first time. fAB2 possessed broad-spectrum lysogenic activity against multidrug-resistant A. baumannii with the advantages of rapid adsorption, short latency and high lysogenicity. And the authors in last one study (Hua et al., 2017) isolated a phage, SH-Ab15519, showed good therapeutic efficacy against carbapenem-resistant A. baumannii lung infection in a mouse model, significantly improving the survival rate of the mice without obvious side effects.

Three other studies characterized the antimicrobial properties of different endolysins (lysins). Lysins are phage-encoded enzymes that degrade the bacterial cell wall at the end of the phage replication cycle, releasing newly assembled phages. They are not as specific as phages, and a single phage-encoded endolysin may be able to lysate a wide range of bacteria. One study (Lood et al., 2015) identified the novel endolysin PlyF307 showed strong bactericidal activity against multidrug-resistant A. baumannii, which not only efficiently cleared planktonic bacteria and biofilm in vitro, but also improved the survival rate of infected mice in a mouse bacteraemia model. One study (Lai et al., 2011) isolated endolysins LysAB2 from A. baumannii phage 6AB2, which exhibited broad-spectrum antibacterial activity against a variety of drug-resistant bacteria, including A. baumannii, by enhancing the permeability of bacterial cell membranes, and possessed good thermal stability. The other study (Oliveira et al., 2016) identified the novel endolysins ABgp46 from the A. baumannii phage vb_AbaP_CEB1 as having a broad-spectrum of antimicrobial activity against drug-resistant Gram-negative bacteria, and the antimicrobial effect was significantly enhanced when combined with citric and malic acids.

In the last study (Briers et al., 2014), artilysins developed through protein engineering successfully breached the outer membrane barrier of Gram-negative bacteria, including A. baumannii, and demonstrated effective bactericidal activity against drug-resistant strains. As we know, the popularity and application of sequencing technology has enabled researchers to discover many new phages (Blasco et al., 2022; Kyriakidis et al., 2021). Further analysis of the unknown functional proteins of A. baumannii phages will facilitate the development of phage-derived enzyme preparations. While second-generation sequencing and gene editing technologies have accelerated the screening and engineering of phages. There is still great potential in this field, despite the limited research on engineered phages that effectively degrade multidrug-resistant A. baumannii (Popova et al., 2019; Shchurova et al., 2021; Vukotic et al., 2020).

It is worth noting that “biofilm” is also one of the high-frequency keywords. Biofilms are composed of bacterial communities encapsulated in a fibrin matrix that impedes antibiotic penetration and enhances environmental adaptation (Leptihn and Loh, 2022). In recent years, the ability to form biofilms has been identified as a central factor in drug resistance and nosocomial infection outbreaks in A. baumannii. It has been shown that phage action on biofilms can disrupt the biofilm matrix, expose bacterial surface receptors and initiate the infection cycle with enhanced antibiotic penetration, resulting in a synergistic bactericidal effect (Hernandez-Morales et al., 2018). Therefore, the study of phages acting on biofilms is particularly necessary. As phages continue to be discovered and characterized to lyse biofilm-associated proteins, many studies have reported the effective elimination of A. baumannii using phage haemolysins or depolymerases (Huang et al., 2014; Oliveira et al., 2016), and although such proteins are unable to replicate themselves, the lower risk of resistance and the significant effect of combination with antibiotics provide new ideas for clinical treatment.

Specifically, phages can specifically lyse CRAB that are ineffective for antibiotics and are suitable for critical infections (Schooley et al., 2017). In addition, by combining with antibiotics, phages can simultaneously improve antibiotic penetration and reduce the occurrence of drug resistance when disrupting biofilms, and the synergistic effect of the two to enhance efficacy can break through biofilm-associated infections (Chan et al., 2016) The bactericidal mechanism of lytic enzymes secreted by phage is different from that of phage itself and antibiotics, and phage enzymes can dissolve more pathogenic bacteria and do not generate resistance, and phage enzyme-related agents may be widely used for biocontrol in the future (Coleman et al., 2012; Lu and Collins, 2007). Phage cocktail therapy, on the other hand, involves screening of matching phages based on strains isolated from patients to achieve personalized treatment and reduce the risk of drug resistance through phage combination therapy (Merabishvili et al., 2014).

However, phage therapy still faces several challenges. These include the limited spectrum of phage lysis and the development of bacterial resistance through rapid mutation of phage receptors (Wang et al., 2023). However, it is encouraging to note that phage cocktail therapy or phage combination therapy may be an effective response strategy. Phage cocktails have been identified as the best solution for clinical applications, but more cocktail combination therapies still need to be explored to identify the most effective cocktails and further elucidate the combination mechanisms (Caflisch et al., 2019; Cui et al., 2019; Grygorcewicz et al., 2021; Luong et al., 2020a). Combinations of phage and other antimicrobial substances are also promising for the treatment of A. baumannii, including phage-antibiotic combination therapies (Grygorcewicz et al., 2020), phage-natural antimicrobial combination therapies (Wintachai and Voravuthikunchai, 2022), and even phage-photosensitizer combination (Ran et al., 2020). However, further experimental studies are needed to determine the optimal combination regimen and application strategy (Gordillo Altamirano et al., 2022; Grygorcewicz et al., 2021).

More seriously, the high host specificity of phages makes it challenging to prepare phage cocktails in advance, and current cocktail therapies still require the implementation of highly individualized regimens, which leads to high investment in screening specific phages and subsequent treatment (Mattila et al., 2015). In addition, because of the widespread lack of a theoretical mechanism system for phage therapy, the current lack of authoritative guidelines or consensus on clinical application, and the possible risk of endotoxin release in the treatment of Gram-negative drug-resistant bacteria, many patients do not agree to be treated with phages. This is one of the major reasons why phage therapy has not been approved as clinical drug therapy (Knoll and Mylonakis, 2014; Schooley et al., 2017).

The rapid emergence of bacterial resistance to phages makes the application of phage therapy crucial. Therefore, there is a need for basic research, including the characterization of phage host receptors and the molecular mechanism of phage resistance in A. baumannii. In the future, phage therapy needs to promote the establishment of a global phage resource sharing platform based on the analysis of bacterial phage interaction mechanisms. Through the integration of precise targeting, synergistic antimicrobial agents and technological innovation, phage therapy is expected to break the multidrug resistance dilemma and open a new avenue for anti-infection treatment.

This study also has some limitations. Firstly, the literature was only retrieved from the WOSCC database, which may have resulted in an incomplete search. However, this database is one of the largest and most comprehensive databases in the world and is the most commonly used source of literature in bibliometric analyses, and the size of its data is sufficient to reflect the current state of research in the field. Secondly, we only selected studies published in English. Finally, some citation metrics in bibliometric analyses may be somewhat biased because citations are affected by various factors, such as time windows, self citation, author authority, journal impact and open access status (Urlings et al., 2021). For example, because of the lag in citations, the number of cited studies in recent years is relatively small.

In summary, we performed bibliometric analyses using various statistical software to obtain an overview on phages in A. baumannii infections. We enumerate the characteristics of publications, show the most influential countries, institutions, authors, and journals, and visual the research hotspots in the field of phage therapy along with their application for the prevention and treatment of A. baumannii infections. In addition, we discuss the advantages and challenges faced by phages in the control of A. baumannii infections. Phage therapy can be a powerful tool for the treatment of A. baumannii infections.