Spatial, Ecologic, and Clinical Epidemiology of Community-onset, Ceftriaxone-resistant Enterobacteriaceae, Cook County, Illinois, USA

Vanessa Sardá; William E. Trick; Huiyuan Zhang; David N. Schwartz

Disclosures

Emerging Infectious Diseases. 2021;27(8):2127-2134. 

In This Article

Discussion

Our study has 4 main findings. First, compared with patients from whom CTX-susceptible community-onset Enterobacteriaceae isolates were collected, patients with CTX-R isolates more often were male, were 35–85 years of age, had self-identified race and ethnicity other than non-Hispanic Black, were hospitalized rather than discharged from the ED or seen in clinic, and resided in Cook County census tracts with higher proportions of foreign-born residents. Second, most patients with CTX-R isolates resided in a relatively small number of census tracts, with only 11% of Enterobacteriaceae isolate–generating census tracts accounting for 54.2% of CTX-R isolates and 93 (8.6%) of E. coli isolate–generating census tracts accounting for 49.7% of all CTX-R E. coli isolates. Third, spatial analysis supported the nonrandom distribution of Cook County census tracts generating higher proportions of ceftriaxone resistance among Enterobacteriaceae and E. coli isolates. Fourth, the population-level characteristics of census tracts from which isolates of CTX-R Enterobacteriaceae and E. coli were obtained differed from residents of census tracts yielding susceptible isolates exclusively, with the percentage of Hispanic residents, foreign-born, and uninsured population being positively associated with the presence of CTX-R isolates on analysis in both cohorts.

Similar to our findings, spatial studies conducted abroad of drug-resistant Enterobacteriaceae have shown nonrandom spatial distribution of antimicrobial-resistant Enterobacteriaceae in large urban areas. A study from São Paulo, Brazil,[20] identified hotspot clusters of ciprofloxacin-resistant E.coli isolates that were associated with population-level ciprofloxacin usage. A study from Japan[21] also showed clustering of levofloxacin-resistant E. coli isolates in the western part of the country, also associated with population-level quinolone usage. In Chicago, residence in the northwest and southern region of Chicago (and adjacent suburbs) was independently associated with increased likelihood of infection by CTX-M-9 Enterobacteriaceae isolates in children.[22]

Our individual-level analysis showing that ceftriaxone resistance was associated with increasing age and male sex is consistent with data reported elsewhere[8,23] and might reflect unmeasured associated underlying conditions, especially those involving the genitourinary tract[8,24] and antibiotic exposures.[8,25–27] Unmeasured underlying conditions and associated antibiotic exposure could also account for the strong association between ceftriaxone resistance and the need for hospitalization, although the increased virulence observed in circulating ESBL-producing clones[28] could account for this finding.

The associations between self-reported Hispanic ethnicity and CTX-R Enterobacteriaceae and E. coli identified in the individual-level analysis and ecologic analyses merit further scrutiny. First, the correlation of Hispanic ethnicity and foreign-born status at a population level (r = 0.69) suggests that these 2 communities are highly interrelated; indeed, ≈45.6% of foreign-born persons in Cook County are noted to have emigrated from Latin America.[19] Therefore, patients who self-identified as Hispanics also might have been foreign-born and might have become colonized by resistant organisms before emigration from or during travel to Latin American countries, some of which have reported high prevalence of ESBL-producing Enterobacteriaceae.[5,29,30] This same pathway could explain the similar association between the proportion of foreign-born population in a census tract and likelihood of ceftriaxone-resistance in the ecologic and individual-level analyses. In addition, a sizable proportion of non–US-born Cook County residents emigrated from countries in Asia (27.3%) and fewer emigrated from Africa (3.2%),[19] continents with variable but often high prevalence of drug-resistant Enterobacteriaceae[3,4] (We did not include other racial and ethnic population-level characteristics in our individual-level analysis because of multicollinearity with individual-level race and ethnicity). Second, Hispanics residing in the United States have been reported to use antibiotics without prescription more frequently than other racial and ethnic groups.[31] Third, we cannot discount that proximity of Hispanic communities, foreign-born communities, or both to environmental sources, such as contaminated waterways, might be an important added risk factor for colonization or infection by drug-resistant Enterobacteriaceae in these areas.

Although in our ecologic analysis the percentage of households beneath the poverty line was not significantly different between census tracts from which CTX-R Enterobacteriaceae or E. coli isolates were and were not generated, observed associations between the percentage of uninsured residents and the presence in census tracts of CTX-R isolates suggest that census tract-level deprivation might predispose to antimicrobial-resistant infections. In the analysis limited to E. coli isolates, overcrowding percentages were also associated with antimicrobial-resistant infections, suggesting possible household-level transmission. A recently published study by Otter et al. from London[27] identified associations between community-level variables, individual-level variables, and likelihood of ESBL rectal colonization among patients admitted to the hospital. In their analysis, only recent overseas travel, recent antimicrobial use, and community-level overcrowding rates were associated with ESBL rectal carriage, whereas individual- and community-level race, ethnicity, and immigration characteristics were not. The paucity of spatial and ecologic studies of antimicrobial-resistant Enterobacteriaceae in the United States makes it difficult to establish whether our results are representative of the urban epidemiology of these organisms in the country. Although not directly comparable because of a difference in outcomes, the discrepancy of our findings and those reported by Otter et al.[27] suggest that the effect of population-level variables might remain distinct in different geographic areas.

Our findings are limited by the fact that our isolates were obtained in a single healthcare system. As a safety-net healthcare system, CCH is likely to be subject to geographic bias already because our patients do not come equitably from all census tracts in Cook County. The paucity of isolates from Cook County communities that do not obtain services from our healthcare system limits the generalizability of our findings regionally. We were unable to gather data regarding risk factors for healthcare-associated infections (such as recent hospitalization) and recent antimicrobial use, both important limitations. In addition, the relatively small sample size and high correlation between population-level factors made meaningful multivariable analysis infeasible. We were unable to perform genomic analysis of CTX-R organisms, which would have enabled us to evaluate the relatedness of isolates and make stronger inferences about whether spatial clustering was related to a point source or interpersonal transmission. Finally, the limited number of clinical and population-level variables included in the individual risk analysis prevents definite conclusions regarding individual risk for CTX-R infection among our patients. Indeed, concurrent assessment of other well-known individual risk factors, such as recent travel or antimicrobial use, could alter the effect size of ecologic variables. Nevertheless, our findings corroborate previous investigations that have identified important community-level variation in CTX-R infection risk in association with geographic,[20–22] demographic,[7,23–25] and population-level variables.[27] Developing effective mitigation strategies, such as focusing antimicrobial stewardship efforts on affected areas, including residence as a risk factor in treatment-decision algorithms, or identifying and eradicating local environmental sources of drug-resistant pathogens, could well depend on improved understanding of these dynamics.

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