Global trend and multidisciplinary impact of UTI linked with E. coli
Antibiotic resistance has emerged as one of the most concerning public health issues of the 21^st century. According to the recent report published by the World Health Organization (WHO), the alarming rise of the AMR is compromising the effective prevention of a wide range of infections globally.¹ Furthermore, the Global Antimicrobial Resistance and Use Surveillance System (GLASS) also highlighted global resistance rate of the traditional antibiotics against the infections linked with the Gram-negative pathogens.²⁴ To improve the therapeutic outcomes and to determine the heterogenicity of the global resistance pattern necessitates the substantial global surveillance of the AMR trends.²⁵ Previous literature has established the UTIs as the most common yet prevalent one amongst the broader AMR landscape.²⁶ Due to the increasing rate of AMR, hundreds of millions of individuals worldwide suffering from UTIs are experiencing treatment failure, recurrent infections, and prolonged hospital stays, thereby significantly disrupting socio-economic stability.²⁶ Often in serious recurrent cases, these UTIs accounts for the development of pyelonephritis, urosepsis and even death.²⁷ Additionally, UTIs represents a significant proportion of all infections which require frequent hospitalization and medical attention. Furthermore, the disease burden linked with UTIs is also unevenly distributed among the women, older people, and individuals with comorbidities.²⁸ In earlier times, UTIs were generally considered non-threatening ones, but the rising prevalence of AMR has significantly compromised the management strategies, leading to heightened risk associated with adverse clinical outcomes. E. coli is accountable for approximately 70%-90% of the UTIs and considered as the most prevalent etiological agent amongst the other pathogens.² The organism’s ability to thrive within the detrimental environmental conditions and secrete a plethora of virulent determinants (including adhesins, toxins, iron-acquisition system etc.) making it as the persistent one.²⁹ Clinically, the UTIs associated with E. coli are notable for the acquisition and spreading of the resistance determinants, including extended spectrum beta-lactamases (ESBLs), fluoroquinolones, and carbapenems.³⁰ To address this, the global trend analysis of AMR, evolutionary adaptability and epidemiological dominance linked to UTI-associated with E. coli is necessary to inform the empirical therapeutic strategies and to support the antimicrobial stewardship program initiated by the GLASS. Therefore, in this present study, efforts have been made to analyze the bibliometric trends of ~50,000 research articles. The bibliometric trend represented in Figure 1A provides crucial insights into the response of the scientific community towards the escalating threat linked with E. coli associated UTIs. Briefly, following the discovery of E. coli mediated UTIs in 19^th century, the annual publication counts (expressed as blue bars in Figure 1A) gradually increased from the 1970s to late 1990s. After the 20^th century, the publication count was substantially increased (Figure 1A). This sharp rise in the publication count is correlated with the global recognition, awareness and surveillance of the E. coli resistance to the cephalosporins and fluroquinolones. However, the steep rise in the publication count over the last decade underlines the intensified research efforts to comprehend the resistant mechanisms, epidemiological trends, and clinical outcomes attributed to the UTIs associated E. coli (Figure 1A). Additionally, the trajectory of mean citations per article (represented as the red line in Figure 1A) represents an entirely different trend. The bibliometric analysis revealed that the citation impact was found to be comparatively higher during the time period of 1990s, probably due to the groundbreaking research that established the basic concepts linked with the pathophysiology of UTIs associated E. coli and their antibiotic resistance (Figure 1A). In contrast, the average citations per article significantly decreased in the post-2000 due to the higher publication volume (Figure 1A). This decreased rate reflects the dilution of the citation impact due to the rapid expansion of the research field. Taken together, the mean citations per article trend represents a significant shift from an era dominated by the small number of groundbreaking studies to a mature research area characterized by large-scale surveillance reports, regional studies and gradual advancements, rather than suggesting the stature of scientific quality. Figure 1A depicts that the antibiotic resistance linked to UTI-associated E. coli has been globally emerged as a significant research area. The field’s development and diversification are reflected in the marked shift in citation dynamics, while the exponential growth in publication output underscores the escalating clinical burden associated with antibiotic-resistant UTI-causing E. coli. This bibliometric increase is in line with the GLASS and WHO priorities, highlighting the urgent need for robust global trend analysis to address the persistent threat linked with this high-quality pathogen by using empirical therapeutics and to establish antimicrobial stewardship at global scales.

Additionally, to comprehend the global epidemiology linked with AMR burden, country-wise publication output reflects the necessary information.³⁰ In many cases, high research publications of any country are commonly driven by the increasing reports of treatment failure, rising prevalence of multidrug-resistant pathogens in that specific region.³¹ This significant increase in the research productivity necessitates the upgradation of national empirical treatment guidelines. Therefore, the country’s wise publication trend represents an indirect indicator of the extent of UTIs mediated threats posed by E. coli. In the present study, efforts have been given to understand the country’s wise prevalence of UTIs associated with E. coli over the period from 1970 to 2025. The observations of the same revealed a substantial heterogenicity of publication output across the geographical regions (Figure 1B). The top contributors to the publication outputs linked with global burden of E. coli associated UTIs are the United States and China, followed by India and European regions including France, Italy, Germany, and United Kingdom. In these geographical regions, sustained and high number of scholarly publications indicates the reflection of increased number of E. coli associated with UTIs, and overuse of antibiotics (Figure 1B). Notably, the significant contribution of China and India might be the reflection of the critical burden of UTIs due to their huge population and the increase in the resistance to the first line medications like cephalosporin and fluoroquinolones. According to the bibliographic analysis, post 2020, the research output has shifted drastically in global context amongst the high-income and emerging economics (Figure 1B). Whereas prior to 2020, most of the research linked with E. coli associated with UTIs was conducted in Western Europe and North America (Figure 1B). The observed publication pattern indicates that the emergence of UTIs was identified earlier in these geographical regions and subsequently examined more rigorously. Since 2020, the publications from geographical regions like China, India, Brazil, Iran, Malaysia, and Egypt have increased significantly (Figure 1B). This bibliometric analysis represents increasing emergence of UTI-associated complications in those areas which were not previously reflected in the literature. The heightened numbers of publications in such areas are probably a reflection of the increasing efforts to combat the AMR threats linked with E. coli mediated UTIs. Taken together, these bibliometric findings reveal that publication trends across geographical regions closely follow the epidemiological dynamics of E. coli-associated UTIs. This increasing rate of publication linked with E. coli associated UTIs revealed a major shift of E. coli mediated UTIs from specific geographical issues to a global concern.

Global trends of antibiotic resistance in UTIs linked with E. coli
Trends in AMR among E. coli-associated UTIs have substantial clinical implications for treatment outcomes and broader socio-economic stability.²⁹ To treat UTIs, medical professionals often provide the repeated prescriptions and subsequent use of expensive drugs, including carbapenem. In global context, the low- and middle-income countries are getting affected drastically due to unavailability and less access towards the advanced therapeutic regimens.³² Hence in those geographical regions, the morbidity rate is significantly rising due to the relatively low percentage of people getting proper treatments. The systematic evaluation of the antibiotic-resistant pattern over time is highly required to offer a precise therapeutic guideline on a global scale. Therefore, in this present study, efforts have been made to analyze the global compositional perspective reporting the antibiotic resistance evidence associated with UTIs linked with E. coli by analysing the abstracts from the ~50,000 research articles. The global distribution of resistance trends indicates that most first-line antibiotics, including aminoglycoside, trimethoprim/sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, have exhibited increasing resistance over time (Figure 2A). Despite the increasing resistance trends over time, these antibiotics are widely used to treat UTIs mediated threats, further corroborating the AMR threat linked with UTIs. Additionally, the resistance trends of the beta-lactam and carbapenem group of antibiotics is concerning, as these were considered as the last resort medications to treat UTIs linked with E. coli (Figure 2A). Furthermore, the temporal dynamics in the antibiotic-resistant trend over the time period of 1973-2025 is crucial to understand the emergence, and persistence of resistance towards any specific antibiotics which cannot be understood through the cluster tree map represented in Figure 2A. To comprehend the same, the year wise heatmap of antibiotic resistance trend exhibits the emergence and gradual escalation of resistance for fluoroquinolones, cephalosporins, and aminoglycosides since 1970s (Figure 2B, Table 1). Additionally, the antibiotic resistance heat map also significantly reported the recent trend of resistance linked with carbapenems and fosfomycin which is gradually increasing (Figure 2B). In recent times, medical professionals often prescribed traditional antibiotics based on outdated routine knowledge even in the absence of accurate culture results. Due to this lack of resistance analysis, the patients often received inappropriate therapeutics, and the intensive selection of superbugs is rising globally. This clinical situation further intensifies the silent pandemic of AMR linked with UTIs. Hence, to mitigate the complexity linked with treatment failure, a comparative understanding of early (1970-1999) and recent (2000-2025) resistant trend is highly required. In this regard, the observations of Figure 2C highlighted the divergence of antibiotic resistance over time. Briefly, a few antibiotics exhibit steady resistance patterns whereas, some antibiotics (ciprofloxacin, cephalosporin, and carbapenems) exhibit a sharp increase in the resistance pattern (Figure 2C). This global observation represents the consequence of overuse of antibiotics and rising prevalence of antibiotic resistance. Taken together, this comprehensive analysis revealed a systematic trend of antibiotic resistance in UTIs linked with E. coli. Furthermore, to comprehend the treatment regimens, estimation annual percentage change (EAPC) is highly required for quantification of temporal change in AMR and advancement in the identification of priority antibiotics to mitigate the resistance burden.

Table 1. Emergence of antibiotic resistance against UTIs associated with E. coli

Quantitative long-term dynamics in AMR threats associated with E. coli mediated UTIs
EAPC estimation helps to understand the AMR trends of E. coli mediated UTIs as resistance generally occurred through temporal and non-linear mechanism.¹⁸ This estimation can effectively measure the AMR by analysing the rate and degree of change in comparison with the global trend. Hence this longitudinal analysis helps to distinguish the effective antibiotics over a pool of traditional antibiotics for better patient outcomes by transforming heterogenous bibliometric resistance trends into simple interpretable trends.¹⁸ Additionally, the EAPC estimation also supports cross-antibiotic ranking and provides early warning signals for last-resort antibiotics. In this regard, this study aims to analyse the trend of resistance rate over a period of time by estimating the EAPC for every antibiotic. The computed EAPC indicates a positive EAPC rate in terms of several antibiotics, including carbapenems, fosfomycin and piperacillin-tazobactam (Figure 3A, Table 2). This positive EAPC rate suggests an increasing resistance rate and also provides the selective pressure of these antibiotics in clinical outcomes globally. Additionally, as represented in
Figure 3A and Table 2, the trend of resistance rate in fluoroquinolone and cephalosporin represents the trend of selective E. coli over a long period of time. Furthermore, the traditional resistance agents exhibit a negative EAPC rate, suggesting their reduction as potent therapeutic agents. To complement the computed EAPC, the relative ranking of the antibiotics between early and recent periods were also determined (Figure 3B). This rank-shift analysis of antibiotics helps to find out the relative changes in the resistance metrics. Figure 3B reveals that carbapenems and fosfomycin are tending to represent upwards shifts in terms of recent rankings. This observation underscores the clinical relevance of resistance despite its relatively late emergence. In contrast, several antibiotics exhibited a downward shift in ranking, likely reflecting their replacement in frontline treatment regimens (Figure 3B). Taken together, this analysis helps to understand the changes in the treatment regimens and adaptation of resistance in UTIs associated with E. coli. Furthermore, the persistence of AMR is also important to find out the less effective antibiotics and replace them with more promising antimicrobial agents. In this regard, Figure 4 exhibits that gentamicin, nitrofurantoin, and amikacin contributed higher in the persistence factor analysis. This observation suggests that the efficacy of these antibiotics against the UTIs associated with E. coli is seriously compromised. In contrast, the lower persistence rates observed for newly introduced antibiotics may reflect a rapid rise in the emergence of AMR (Figure 4). Taken together, the integrated trend analysis and persistence profiling provide a comprehensive assessment of the complexity of AMR in E. coli-associated UTIs, highlighting antibiotic-specific differences in resistance dynamics. Overall, this study highlights the dynamic and heterogenous trajectory of AMR in UTIs linked with E. coli. This rapid emergence of resistance to several traditional and front-line antibiotics emphasizes the importance of continuous surveillance and emergence of novel therapeutic agents to address the rising threats linked with resistant UTIs.

Table 2. EAPC trend of the antibiotics