Introduction
Antimicrobial-resistant (AMR) infections contributed to 1.27 million deaths globally in 2019. Reference Murray, Ikuta and Sharara1,2 The World Health Organization predicts that this number may increase to 10 million deaths by the year 2050, with antimicrobial resistance occurring shortly after new drugs are approved for use. Reference Mancuso, Midiri, Gerace and Biondo3,Reference Reygaert4 Third-generation cephalosporins (3GCs) are broad-spectrum antibiotics widely used to treat infections with gram-negative bacteria and are preferred due to their low incidence of adverse effects. Reference Bush and Bradford5,Reference Watkins, Bonomo, Cohen, Powderly and Opal6 3GCs are especially successful in treating infections caused by Enterobacterales and are recommended for treatment of urinary tract infections (UTIs). Reference Arumugham, Gujarathi and Cascella7 However, resistance to 3GCs has become increasingly common, largely due to the rapid spread of extended-spectrum beta-lactamase (ESBL) enzymes among Enterobacterales. 8 3GC-resistant (3GC-R) Enterobacterales were labeled a “critical priority” by the World Health Organization in 2024 and a “serious healthcare threat” by the Centers for Disease Control and Prevention in 2019. 8–Reference Rawat and Nair10
UTIs are common, and drug-resistant UTIs can prolong hospital stays, increase costs, and raise mortality. Reference Al-Badr and Al-Shaikh11–Reference Dunne, Puttagunta, Aronin, Brossette, Murray and Gupta14 There is growing interest in how the social determinants of health intersect with patients’ risk for colonization and community-acquired infection with AMR pathogens like 3GC-R Enterobacterales. Reference Blackmon, Avendano and Nirmala15,16 There is no biological basis for differences in these outcomes due to race or ethnicity, but disparate impacts of structural racism and the social determinants of health (SDOH) on individuals of distinct identities, such as inequitable access to quality healthcare and health insurance coverage, are critical to analyze. Reference Avendano, Blackmon and Nirmala17,Reference Yearby, Clark and Figueroa18 A recent study found that Hispanic, Black, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islanders were more likely to live in crowded households compared to White people, and household crowding has previously been found to contribute to the spread of UTIs caused by ESBL-producing E. coli, for example. Reference Ndugga, Hill and Artiga19,Reference Paumier, Asquier-Khati and Thibaut20 Due to the limited number of studies that connect the SDOH to disparities in community-acquired 3GC-R uropathogens specifically, it is important to analyze and summarize evidence on the racial and ethnic differences in the risk of community-acquired 3GC-R uropathogens.
The goal of this systematic review and meta-analysis (SRMA) was to synthesize available evidence on differences in the risk of community-acquired 3GC-R uropathogen prevalence across racial and ethnic groups. The specific question guiding the SRMA was: how does the risk of colonization or community-acquired infection by 3GC-R uropathogens differ across race and ethnicity?
Methods
Search strategy and selection criteria
This SRMA builds on a completed scoping review of the association between race, ethnicity and risk of colonization or community-acquired infection with ESKAPE pathogens (ie, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and Escherichia coli. The search strategy for the prior scoping review involved a comprehensive search in MEDLINE (Ovid), MEDLINE Epub Ahead of Print, In-Process, In-Data-Review and Other Non-Indexed Citations, and Daily (Ovid), Global Health (Ovid), Embase (Elsevier), Cochrane Database of Systematic Reviews (Wiley), Cochrane Central Register of Controlled Trials (Wiley), and Web of Science Core Collection (Table S1). Reference Avendano, Blackmon and Nirmala17 The initial search was conducted in January 2022 and updated with a slightly modified search strategy through March 2024 (Supplementary Methods, Modified Search Strategy).
For this SRMA, we included studies identified through the scoping review that reported 3GC-R bacteria in urine or urinary tract infections as the outcome. Inclusion and exclusion criteria are reported in Table 1. Included studies reported raw case counts or calculated effect measures (odds ratios or risk ratios) on community-acquired 3GC-R uropathogens by race/ethnicity. An additional hand-search was conducted in August 2024 by searching through the reference sections of each included study and using Google Scholar to identify papers that cited the included studies. The protocol for this SRMA was registered in PROSPERO as CRD42024536522.
Inclusion and exclusion criteria for parent scoping review and this SRMA
Screening, data extraction, and synthesis
Two reviewers screened titles and abstracts before advancing the publication to full text review and proceeding to data extraction following the PRISMA guidelines. A customized data extraction form created in Covidence captured study characteristics, inclusion and exclusion criteria, study definition of community-acquired infection, method of recruitment, method of exposure measurement, case counts, and effect measures. A third reviewer among the team settled disagreements during the process. A modified form was created to extract data from included papers identified through the hand-search (Table S2). For this SRMA, studies were included from the scoping review if they reported raw case counts or effect measures for community-acquired 3GC-R uropathogens, bacteriuria, or urinary tract infections by race/ethnicity. Extracted data included the number of patients within each racial or ethnic category who tested positive for 3GC-R uropathogens, 3GC-R bacteriuria and/or 3GC-R UTI, including patients who tested positive for ESBL-producing bacteria in their urine.
Risk of bias assessment
A modified Newcastle-Ottawa Quality Assessment Scale (NOS) was used to conduct risk of bias (ROB) assessments for the cohort and case-control studies included in the systematic review, respectively (Supplementary Materials, Table S3, Table S4). Reference Wells, Shea and O’Connell21 Three indicators with 1–4 questions each were used to assess ROB for each study, and scores were combined for each indicator to categorize studies into low, moderate, or high ROB. SBa and SBl independently completed the ROB assessment for each paper, including relevant justifications. SBa conducted a consensus of the completed assessments by categorizing each study’s ROB level (Supplementary Materials, Table S5).
Statistical analysis
Study characteristics were summarized using RStudio (version 4.3.1) (Table 2). Meta-analyses were conducted when at least three studies reported data on 3GC-R uropathogen prevalence across racial and ethnic groups. Non-Hispanic White or Caucasian persons were chosen as the reference group for each. The metagen function within the “meta” package version 7.0 was used to conduct a random-effects model for each meta-analysis in RStudio. The metagen function was used because of its ability to pool precalculated effect measures from studies by including log effect measures and their standard errors, rather than raw case counts. Reference Schwarzer24 For studies that reported case counts, we manually calculated risk ratios, 95% confidence intervals, and standard errors in Microsoft Excel to compare the risk of 3GC-R uropathogens between each minority racial/ethnic group versus White/Caucasian persons, respectively.
Characteristics of studies included in this systematic review
a All studies included non-ESBL-producing bacteria or non-3GC-R bacteria as comparison groups.
Forest plots for each meta-analysis included the pooled risk ratio and 95% confidence interval, I2 value to measure heterogeneity, τ2 value to measure between-study variance. The plots visually depicted each study’s individual risk ratio relative to the pooled risk ratio.
Results
Study characteristics
Five studies were included in this SRMA (Figure 1). Reference Raphael, Glymour and Chambers25–Reference Collingwood, Yarbrough, Boppana and Dangle29 Three studies were included from the 104 eligible studies identified in the previously mentioned scoping review. Reference Raphael, Glymour and Chambers25–Reference Megged27 Two additional studies were identified by hand-searching Google Scholar for papers that cited the already included studies. Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 Most studies were excluded because they did not report on race/ethnicity or urine specimens.
PRISMA flowchart for selection of articles in the systematic review and meta-analysis.
Systematic review
Study characteristics are summarized (Table 2). Patients’ race and ethnicity were collected through electronic medical records for all included studies, though it was not specified whether race or ethnicity was self-reported by patients. Based on the precalculated and manually computed risk ratios, there was generally a higher risk of 3GC-R uropathogens among Hispanic/Latinx persons Reference Raphael, Glymour and Chambers25,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28 and Asian persons Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 compared to White persons. The risk of 3GC-R uropathogens among Black and African American persons was generally equal to or lower than the risk among White persons. Reference Raphael, Glymour and Chambers25,Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26,Reference Collingwood, Yarbrough, Boppana and Dangle29 One study found a significantly higher risk of ESBL-producing E. coli bacteriuria among Latinx persons (n = 2 335) compared to White persons (n = 918) when adjusting for age, gender, and patients’ preferred language. Reference Raphael, Glymour and Chambers25 Study authors hypothesized that the heightened risk of ESBL-producing E. coli bacteriuria among Latinx persons was a result of increased access to antibiotics among this population and/ or increased travel from countries like Mexico, a country with high prevalence of community-acquired infections caused by ESBL-producing E. coli.
Another study found a statistically significant association between Middle Eastern ethnicity and odds of ESBL-producing E. coli UTI when adjusting for presence of genitourinary abnormalities, history of antibiotic usage in the last three months, vesicoureteral reflux, and prior UTI in the last three months, among 214 children receiving treatment in the northwestern USA. The authors also proposed travel (to the Middle East and North Africa) as a possible risk factor. Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26 Another study found a significantly higher odds of pediatric ESBL-producing Enterobacteriaceae UTI among persons of Arab descent (n = 59) compared to persons of Jewish/non-Arab descent (n = 101) when adjusting for recent antibiotic use, possibly due to congenital multiple anomalies, lower socioeconomic status, and relatively poorer sanitation in predominantly Arab villages according to the study authors. Reference Megged27
One study found that, between the years 2015 to 2020, the incidence of pediatric ESBL-producing E. coli UTI among White and Black persons included in the study increased by 85.5% and 65.5% per year, respectively, though there was not a statistically significant difference in the yearly percent changes between White and Black persons. Overall, this study determined an alarming increase in pediatric ESBL-producing E. coli UTIs across all included races. Reference Collingwood, Yarbrough, Boppana and Dangle29
Risk of bias outcomes
After completing the modified NOS assessments, one of the three retrospective cohort studies was determined to have low ROB, while the other two were determined to have moderate ROB. Both case-control studies were determined to have low ROB. The reason for higher ROB among the retrospective cohort studies were: no statistical analysis performed to specifically examine the association between race/ethnicity and 3GC-R uropathogens, unclear indication as to whether the outcome of interest was absent at the start of the study, and no explanation as to how missing data were handled in the analysis.
Meta-analysis findings
Three random effects meta-analyses were conducted to calculate pooled effect measures for the risk of 3GC-R uropathogens among Hispanic/Latinx versus White individuals (n = 3), Black/African American versus White individuals (n = 4), and Asian versus White individuals (n = 3) (Table 3). Due to the limited number of low ROB studies that provided case counts or effect measures for 3GC-R uropathogens across similar racial/ethnic groups, sensitivity analyses limited to low ROB studies were not conducted.
Studies included in each meta-analysis
Hispanic/Latinx versus White/Caucasian
Three studies were included in this meta-analysis, Reference Raphael, Glymour and Chambers25,Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28 comprising 9,585 patients treated in emergency departments, admitted to hospitals, or seen in outpatient clinical settings in California and Michigan from 2012 to 2020. One study Reference Collingwood, Yarbrough, Boppana and Dangle29 was not included in the meta-analysis, because zero Hispanic patients were found to have ESBL-producing E. coli uropathogens, and a risk ratio could not be calculated. Hispanic/Latinx individuals had 1.27 (95% CI RR 1.04, 1.55) times the risk of 3GC-R uropathogens compared to White individuals. This meta-analysis produced an I2 value of 0% with a P value of .45 indicating low heterogeneity, though not statistically significant (Figure 2).
Forest plot of meta-analysis on the risk of 3GC-R uropathogens between Hispanic/Latinx versus White/Caucasian individuals. Note: RR, risk ratio; SE, standard error; CI, confidence interval. Plot was generated using the meta package in R.
Black/African American versus White/Caucasian
Four studies were included in this meta-analysis, Reference Raphael, Glymour and Chambers25,Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 comprising 10,745 patients treated in emergency departments, admitted to hospitals, or seen in outpatient clinical settings in California, Alabama, and Michigan from 2012 to 2021. This meta-analysis indicated no difference in the odds of 3GC-R uropathogens among Black/African American versus White/Caucasian individuals (RR:1.00, 95% CI .84, 1.24), with low heterogeneity (I2 = 0, P val = .66) (Figure 3).
Forest plot of meta-analysis on the risk of 3GC-R uropathogens between Black/African American and White/Caucasian individuals.Note: RR, risk ratio; SE, standard error; CI, confidence interval. Plot was generated using the meta package in R.
Asian versus White
Three studies were included in this meta-analysis, Reference Raphael, Glymour and Chambers25,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 comprising 13,878 patients treated in emergency departments, admitted to hospitals, or seen in outpatient clinical settings in California and Alabama from 2014 to 2021. Although the risk of 3GC-R uropathogens was found to be higher among Asian versus White individuals (1.88 95% CI .69, 5.14), this difference was not statistically significant. This analysis produced high heterogeneity (I2 = 86.3, P val<.01) (Figure 4).
Forest plot of meta-analysis on the risk of 3GC-R uropathogens between Asian and White individuals. Note: RR, risk ratio; SE, standard error; CI = confidence interval. Plot was generated using the meta package in R.
Discussion
To our knowledge, this is the first SRMA on race and ethnicity and risk of community-acquired 3GC-R uropathogens. Overall, Hispanic/Latinx individuals were found to be at significantly higher risk of harboring 3GC-R uropathogens compared to White/Caucasian individuals. There was no difference in risk between Black/African American versus White/Caucasians, and while Asian persons were often found to be at higher risk than White individuals among studies included in our systematic review, this difference was not statistically significant in the meta-analysis.
Previous literature points to disparities in antibiotic resistant uropathogen risk between non-White and White persons, including higher likelihood of resistance against 3GCs among Hispanic persons compared to Non-Hispanic White persons. Reference Sardá, Trick, Zhang and Schwartz22,Reference Stultz, Francis and Ketron23 A 2015 Morbidity and Mortality weekly report published by the Centers for Disease Control and Prevention found that Hispanic individuals were more likely to obtain their antibiotics from sources besides their healthcare provider or clinic and were generally more likely to be unaware of antibiotic resistance. Reference Francois Watkins, Sanchez, Albert, Roberts and Hicks30 Another study analyzing motivations for non-prescription antibiotic use among Hispanic individuals in Houston, Texas found that many believed that going to the doctor to receive prescribed antibiotics was unnecessary, and many found it difficult to make time to travel to hospitals, wait in long lines, and pay high costs for antibiotics. Reference Laytner, Chen and Nash31 As noted by articles included in our systematic review, international travel may also exacerbate exposures to 3GC-R bacteria among this population. Some members of Hispanic/Latinx communities may frequently travel to Latin American countries, and several studies have identified travel to these regions as risk factors for the acquisition of 3GC-R Enterobacterales. Reference Worby, Earl and Turbett32,Reference Ponce-de-Leon, Rodríguez-Noriega and Morfín-Otero33
No elevated risk of 3GC-R uropathogens was found among Black/African American individuals compared to White individuals in our study. This finding is notable due to historically higher rates of other community-acquired AMR infections, specifically methicillin-resistant Staphylococcus aureus (MRSA) infections among Black individuals compared to White persons. Reference See, Wesson and Gualandi34,Reference Gualandi, Mu and Bamberg35 This finding suggests that the underlying factors driving the spread of MRSA versus 3GC-R uropathogens are likely very different and require future investigation.
Almost no studies included in our systematic review considered socioeconomic factors, in addition to race and ethnicity, as potential risk factors for 3GC-R uropathogen burden. Race and ethnicity have no biological basis but are instead social constructs that greatly affect individuals’ lived experiences and access to goods, services, and opportunities. Reference Flanagin, Frey and Christiansen36 Race and ethnicity have traditionally been used in clinical research as proxy measures for socioeconomic risk factors, although this approach has begun to be questioned. Reference Shaikh, Lee and Stokes37 One recent SRMA assessed the role of race in calculating risk for UTI by replacing race with other risk factors, including history of UTI, duration of UTI, and duration of fever, in a common prediction tool. The authors found that the accuracy of the prediction tool in assessing UTI prevalence among Black versus non-Black pediatric patients was maintained when race was substituted with these additional risk factors, indicating that other factors may be more specific and useful for understanding differences in risk. Reference Mauro, Allen, Dauda, Molina, Neale and Lewis38 In our SRMA, two studies continued to find race and ethnicity to be significant risk factors for 3GC-R uropathogens even after adjusting for recent antibiotic use, patients’ preferred language, or prior UTI. Reference Raphael, Glymour and Chambers25,Reference Megged27 Unknown or unmeasured social determinants of health likely contribute to disparate risks for community acquisition of 3GC-R uropathogens among these minority groups.
This study had several strengths. Firstly, we conducted an extensive literature search that did not restrict studies based on study location or included race/ethnicity groups. We included a hand-search to capture up-to-date literature on race/ethnicity and 3GC-R uropathogens. Furthermore, we had a large, pooled sample size, comprising over 13,000 individuals, allowing our meta-analysis to provide more robust insights into the association between race/ethnicity and 3GC-R uropathogens compared to the results of individual studies. Reference Sriganesh, Shanthanna and Busse39
Our study also had limitations. Firstly, we identified relatively few studies examining race, ethnicity, and risk of community-acquired 3GC-R uropathogens despite 3GC-R Enterobacterales being globally recognized as a serious health threat. 8,9 Additionally, the inclusion of non-US studies in our meta-analysis would have provided a deeper understanding of potential racial and ethnic disparities in these infections in an international context; our main conclusions are limited to the US. Additionally, only one study provided adjusted effect measures analyzing 3GC-R risk between racial and ethnic groups that could be included in the meta-analysis. Reference Raphael, Glymour and Chambers25 We thus calculated unadjusted risk ratios from raw case counts provided by the studies. Adjusting for similar covariates across all studies included in each meta-analysis would have allowed for more comparable effect measures. Articles included in our study mentioned how additional risk factors of harboring AMR pathogens include contaminated meat consumption, diabetes mellitus, invasive urological procedures, and previous urine catheters, though these risk factors were not further analyzed in our referenced articles and were therefore not explored in our study.
Another limitation is that the definitions of racial and ethnic groups likely differed across studies, and it was unclear whether race or ethnicity were self-reported by patients, thereby risking misclassification bias. Three studies Reference Raphael, Glymour and Chambers25,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 defined Black and White as racial categories, while another Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26 used the terms African American and Caucasian, as opposed to Black and White. The terms Black and African American are commonly used interchangeably, though they may not include all the same individuals. Furthermore, three studies Reference Zhu, Rodado, Asmar, Salimnia, Thomas and Abdel-Haq26,Reference Mark, Hung, Salim, Tarlton, Torres and Frazee28,Reference Collingwood, Yarbrough, Boppana and Dangle29 used the term Hispanic, while one Reference Raphael, Glymour and Chambers25 used the term Latinx. Similarly, the terms, Hispanic and Latinx, are often used interchangeably, though the term “Hispanic” comprises individuals with ancestry from a primarily Spanish-speaking country, while Latinx refers to those with ancestry in Latin America. Reference Alexander40 In the meta-analysis, we combined Black individuals along with African American individuals, and Hispanic along with Latinx individuals, though certain individuals may not identify with both Black and African American or Hispanic and Latinx. Finally, we considered “Asian” as a monolithic group, since the included studies did not differentiate between Asian communities who vary in their cultures and spoken languages, potentially masking differences in 3CG-R uropathogen risk among Asian communities.
Conclusion
This SRMA found that Hispanic/Latinx individuals are at higher risk of harboring 3GC-R uropathogens than White individuals in the US. While some studies have hypothesized that differences in diet, comorbidities, catheter use, travel history, non-prescription antibiotic use, or other factors might underlie disparities in risk of 3GC-R uropathogens, future studies must consider these covariates in conjunction with race and ethnicity to further assess this. As antibiotic resistance continues to rise in community settings across the globe, our findings support the need to understand differential impacts across communities so that equitable strategies for prevention and treatment can be designed and implemented.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/ash.2025.10097
Acknowledgements
Not applicable.
Author contribution
MLN and SBa conceptualized the study. MLN, NN, and SD acquired the funding. RM performed the updated literature search. SBa, EA, SB, SAA, and MLN reviewed titles and abstracts, reviewed full texts, and extracted data. SBa prepared the tables and figures. SBa, RM, and MLN wrote the first draft of the manuscript. All authors reviewed the manuscript.
Financial support
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number 5UM1AI104681-11 and -12 from 9/1/2023–11/30/2024. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, or of the primary grantee. Funders had no role in study design; in the collection, analysis, or interpretation of data; on in writing the manuscript.
Competing interests
None to declare.
Ethical standard
Not applicable.
Consent for publication
Not applicable.
Availability of data and materials
Additional tables and figures are available in the Supplementary Material.
Open access
