Community-Onset, Ceftriaxone-Resistant Enterobacteriaceae

In This Article

Abstract and Introduction

Abstract

We performed a spatial and mixed ecologic study of community-onset Enterobacteriaceae isolates collected from a public healthcare system in Cook County, Illinois, USA. Individual-level data were collected from the electronic medical record and census tract–level data from the US Census Bureau. Associations between individual- and population-level characteristics and presence of ceftriaxone resistance were determined by logistic regression analysis. Spatial analysis confirmed nonrandom distribution of ceftriaxone resistance across census tracts, which was associated with higher percentages of Hispanic, foreign-born, and uninsured residents. Individual-level analysis showed that ceftriaxone resistance was associated with male sex, an age range of 35–85 years, race or ethnicity other than non-Hispanic Black, inpatient encounter, and percentage of foreign-born residents in the census tract of isolate provenance. Our findings suggest that the likelihood of community-onset ceftriaxone resistance in Enterobacteriaceae is influenced by geographic and population-level variables. The development of effective mitigation strategies might depend on better accounting for these factors.

Introduction

The continuous rise of infections secondary to extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae in the United States is a complex public health problem and considered a serious threat by the Centers for Disease Control and Prevention.^[1] Recently, the incidence of infections caused by ESBL producers in the United States was noted to have increased by 53.3% during 2019–2017, driven largely by a surge in community-onset cases.^[2] Globally, a similar trend has been described, and developing countries bear a disproportionate burden of infections secondary to these drug-resistant pathogens.^[3–5] The steady increases in rates of infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae persist despite antimicrobial stewardship and infection control efforts.^[6,7]

Initially confined to the healthcare environment, infections caused by ESBL-producing Enterobacteriaceae among patients without previous healthcare exposure have been described since the mid-2000s.^[8,9] This epidemiologic shift has been largely attributed to the emergence of the CTX-M–producing E. coli sequence type (ST) 131 clone, which expanded rapidly throughout the United States and remains the most prevalent ESBL-producing E. coli clone in the community.^[10] In addition to higher virulence and transmissibility of the E. coli ST131 clone, its therapeutic management is particularly challenging because of its associated resistance to commonly used oral antimicrobial drugs such as quinolones and trimethoprim/sulfamethoxazole.^[6,10]

From an epidemiologic standpoint, multiple transmission pathways for community-onset ESBL-producing Enterobacteriaceae have been proposed. Potential sources of acquisition outside of healthcare environments include gastrointestinal colonization after international travel^[11,12] and transmission among household members.^[7,13] In addition, ESBL-producing Enterobacteriaceae have been isolated from foodstuffs,^[14,15] livestock,^[14] and waterways,^[16,17] all of which have been posited as potential sources for human colonization and subsequent infection. A better understanding of the epidemiology of community-onset infections caused by ESBL-producing bacteria across geographic areas can help identify areas with higher disease burden and suggest pathways of transmission and mitigation strategies that are potentially unique to each region. Spatial and ecologic analyses help to address the influence of geography and population-level variables on disease distribution in a given region.

We conducted an epidemiologic analysis of the distribution of community-onset, ceftriaxone-resistant (CTX-R) Enterobacteriaceae from a single healthcare system in Cook County, Illinois, USA. We hypothesized that population-level characteristics are contributing factors for the presence of CTX-R Enterobacteriaceae in a geographic area and at the individual level.

Table 1. Demographic and clinical characteristics of patients from whom selected *Enterobacteriaceae* isolates were collected, Cook County Health healthcare system, Illinois, USA, 2016–2018
Characteristic	No. isolates (%)
Total no. isolates	10,891 (100)
Sex
F	7,853 (72.1)
M	3,038 (27.9)
Age group, y
18–34	2,011 (18.6)
35–51	3,109 (28.5)
52–68	4,092 (37.5)
69–85	1,471 (13.5)
>85	208 (1.9)
Race and ethnicity
Non-Hispanic White	997 (9.2)
Non-Hispanic Black	4,394 (40.4)
Hispanic	4,898 (44.9)
Other	602 (5.5)
Encounter type
Outpatient	5,889 (54.1)
Emergency department	2,890 (26.5)
Inpatient	2,112 (19.4)
Organism
Escherichia coli	7,977 (73.2)
Klebsiella pneumoniae	1,367 (12.6)
Proteus mirabilis	811 (7.5)
Enterobacter cloacae	376 (3.4)
Klebsiella oxytoca	197 (1.8)
Enterobacter aerogenes	163 (1.5)
Specimen type
Urine	9,315 (85.5)
Wound	981 (9.0)
Blood	384 (3.6)
Other	211 (1.9)
Ceftriaxone susceptibility
Susceptible	9,856 (90.5)
Resistant	1,035 (9.5)

Table 2. Population-level risk factors for ceftriaxone-resistant *Enterobacteriaceae* identified in Cook County census tracts, Illinois, USA, 2016–2018
Risk factor	Bivariate analysis
Risk factor	Odds ratio (95% CI)	p value
Non-Hispanic White population	0.98 (0.98–0.99)	<0.01
Non-Hispanic Black population	0.99 (0.99–0.99)	<0.01
Hispanic population	1.02 (1.01–1.02)	<0.01
Foreign-born population	1.02 (1.01–1.03)	<0.01
Households below poverty	1.00 (0.99–1.39)	0.35
Overcrowding	1.16 (0.97–1.39)	0.10
Uninsured population	1.07 (1.05–1.10)	<0.01

Table 3. Population-level risk factors for ceftriaxone-resistant *Escherichia coli* identified in Cook County census tracts, Illinois, USA, 2016–2018
Risk factor	Bivariate analysis
Risk factor	Odds ratio (95% CI)	p value
Non-Hispanic White population	0.99 (0.99–1.00)	0.44
Non-Hispanic Black population	0.98 (0.98–0.99)	<0.01
Hispanic population	1.03 (1.02–1.03)	<0.01
Foreign-born population	1.04 (1.03–1.05)	<0.01
Households below poverty	0.99 (0.98–1.00)	0.24
Overcrowding	1.25 (1.04–1.53)	0.02
Uninsured population	1.08 (1.06–1.11)	<0.01

Table 4. Individual and population-level risk factors for ceftriaxone-resistant *Enterobacteriaceae* in patients, Cook County Health healthcare system, Illinois, USA, 2016–2018*
Characteristic	No. (%) isolates			Bivariate analysis
Characteristic	All	Ceftriaxone-susceptible	Ceftriaxone-resistant	OR (95% CI)	p value
Total no. isolates	10,891 (100)	9,856 (90.5)	1,035 (9.5)
Sex
F	7,853 (72.1)	7,215 (66.2)	638 (5.9)	Referent
M	3,038 (27.9)	2,641 (24.2)	397 (3.7)	1.7 (1.5–1.9)	<0.01
Age group, y
18–34	2,011 (18.6)	1,895 (17.4)	116 (1.2)	Referent
35–51	3,109 (28.5)	2,846 (26.1)	263 (2.4)	1.5 (1.2–1.9)	<0.01
52–68	4,092 (37.5)	3,667 (33.7)	425 (3.8)	1.9 (1.5–2.3)	<0.01
69–85	1,471 (13.5)	1,259 (11.6)	212 (1.9)	2.8 (2.2–3.5)	<0.01
>85	208 (1.9)	189 (90.9)	19 (9.1)	1.6 (0.9–2.7)	0.05
Race and ethnicity
Non-Hispanic White	997 (9.2)	902 (8.3)	95 (0.9)	1.6 (1.2–2.0)	<0.01
Non-Hispanic Black	4,394 (40.4)	4,120 (37.8)	274 (2.6)	Referent
Hispanic	4,898 (44.9)	4,324 (39.7)	574 (5.2)	1.9 (1.7–2.3)	<0.01
Other†	602 (5.5)	510 (4.7)	92 (0.8)	2.7 (2.1–3.5	<0.01
Encounter type
Outpatient	5,889 (54.1)	5,419 (49.8)	470 (4.3)	Referent
Emergency department	2,890 (26.5)	2,655 (24.4)	235 (2.1)	1.0 (0.9–1.2)	0.80
Inpatient	2,112 (19.4)	1,782 (16.4)	330 (3.0)	2.1 (1.8–2.5)	<0.01
Mean % foreign-born population (SD)‡	21.5 (17.0)	21.04 (17.0)	25.8 (16.2)	1.0 (1.0–1.1)	<0.01

*Values are no. (%) except as indicated. OR, odds ratio.
†Other refers to isolates from participants who identified as non-Hispanic and reported race as Asian (3% of all isolates), American Indian/Alaska Native (0.4%), multiple races (0.1%), or unknown race (0.8%).
‡Based on data from 2017 American Community Survey 5-year estimates.¹⁹