Escherichia coli Antimicrobial Resistance in Humans: Comparison
Please note this is a comparison between Version 1 by Chloé Corrie Hans Smit and Version 4 by Mona Zou.

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment.

  • antimicrobial resistance
  • antibiotics
  • One Health
  • risk factor
  • community
  • human
  • Escherichia coli

1. Introduction

Antimicrobial resistance (AMR) is a global problem leading to untreatable infections that occurs by natural selection but is driven by antibiotic exposure in healthcare (humans), agriculture (animals, plants, or food-processing technology), and the environment (sea, soil, drinking water, and wastewater) [1][2][3][4][1,2,3,4]. The use of antibiotics in humans and animals is perceived as the major contributor to the development of AMR [5]. With AMR increasing and new antibiotic development stagnating, problems due to untreatable infections can be expected to increase health-related burdens, including more extended hospital stays, increased healthcare costs, and death [6]. Investigating the interaction between humans, animals, and the environment, as well as between the different sectors involved (e.g., pharmaceutical industry, food industry, water waste companies), using a One Health approach, is of great importance in mitigating resistance [7].
Escherichia coli (E. coli) is a common commensal of the intestinal microbiota in both animals and humans [8][9][8,9] that has received significant attention in the literature [10][11][10,11] due to increasing AMR [12][13][12,13] and death associated with resistance [14][15][14,15]. E. coli infections are caused by extraintestinal and uropathogenic subtypes [16], with uropathogenic E. coli responsible for up to 80% of urinary tract infections [17], the most common infectious disease in the community [18]. Virulence potential varies according to molecular types of bacterial isolates [19]. AMR of E. coli is due to both intrinsic (the outer membrane and expression of efflux pumps) and extrinsic mechanisms (the acquisition of mobile genetic elements or through horizontal gene transfer that assists in capturing, accumulating, and disseminating resistance genes [20]). New antimicrobial resistance genes continuously emerge, leading to multidrug resistance [21][22][21,22]. E. coli can mobilize resistant genes more easily than other bacteria populations and act as a reservoir for AMR genes and mobile genetic elements, and is mainly driven by external factors [12][20][12,20]. It is, therefore, essential to understand the community variables leading to AMR of E. coli.

2. Human Variables

2.1. Antibiotic Use

Of the human-related variables, antibiotic use was most frequently reported as a variable for AMR (Table 12). Most reviews investigating the impact of antibiotic use on AMR E. coli reported a positive association ranging from general antibiotic use increasing the odds by 1.5 and use of fluoroquinolones increasing the odds by 19 times (Table 12). Longer duration of use was associated with increased odds of AMR E. coli, as was the use of multiple courses and mass administration across populations such as HIV-infected adults and young children. The use of β-lactam antibiotics was identified as the most important variable in this category, followed by (fluoro)quinolone- and cephalosporin antibiotics [23][48]. There were no [15][24][15,46] statistical results reported around sulphonamides, trimethoprim [25][26][27][35,42,52], and tetracycline [28][29][37,53] use.
Table 12. Human health variables of E. coli AMR among community-dwelling populations.
Variable Subcategory Number of Participants (Number of Studies Investigating

Variable)
Magnitude of

Association

OR (95% CI)
Importance

Rating *
[23][48] (Table 23).
Table 23. Human living and travel variables of E. coli AMR among community-dwelling populations.
Variable Subcategory Number of

Participants (Number of Studies Investigating

Variable)
Magnitude of

Association

OR (95% CI)
Importance

Rating *
Antibiotic use General antibiotic use 6 studies (NR) 1.51 (1.17–1.94) [15] +
Living standards Lower socioeconomic status 2775 (1 study) 1.33 (1.07–1.75) [34] +
1528 (6 studies) 1.58 ** (1.16–2.16) [24][46
2775 (1 study)]
2.47 (1.08–5.66) [34] 1297 (5 studies) 1.63 ** (1.19–2.24) [24][46]
Day-care attendance NR (6 studies) 1.49 (1.17–1.91) [ 449 (1 study) 1.8 (1.0–3.1) [23][48]
88 studies (NR) 2.33 (2.19–2.49) [30][36]
NR (5 studies) 2.65 (1.70–4.12) [31][41]
172 (1 study) 3.1 (1.4–6.7) [23][48]
484 (1 study) 4.0 (1.6–10.0) [23][48]
300 (1 study) 4.6 (1.9–11.0) [23][48]
140 (1 study) 5.6 (2.1–14.8) [23][48]
Trimethoprim and β-lactams 179 (2 studies) 3.2 (0.9–10.8) [25][35] 0
Beta-Lactam 290 (1 study) 4.5 (1.8–11.0) [23][48] +++
510 (1 study) 4.6 (2.0–10.7) [23][48]
(Fluoro)Quinolone 449 (1 study) 2.1 (0.6–7.3) [23][48] +
200 (1 study) 2.6 (1.3–5.1) [23][48]
140 (1 study) 9.9 (2.2–44.6) [23][48]
290 (1 study) 19.0 (3.3–111.4) [23][48]
Penicillin 7170 (1 study) 0.9 (0.5–1.7) [23][48] 0
408 (1 study) 2.7 (1.2–6.3) [23][48]
Cephalosporin 74 (1 study) 1.5 (5.4–85.2) [23][48] +
200 (1 study) 2.2 (1.01–5.0) [23][48]
408 (1 study) 2.2 (1.1–4.5) [23][48]
200 (1 study) 3.9 (1.8–8.5) [23][48]
Macrolides 7170 (1 study) 1.5 (1.1–2.2) [23][48] 0
31][41] 0
Living in Northern vs. Southern Europe 7170 (1 study) 0.4 (0.2–0.7) [23][48] 0
Travel International travel 1887 (6 studies) 4.06 ** (1.33–2.41) [24][46] +++
834 (1 study) 21 (4.5–97) [23][48]
To Asia NR (4 studies) 1.78 (0.64–4.98) [15] ++ Nitrofurantoin 7170 (1 study) 1.54 (1.1–2.3) [
, raw vegetable consumption showing mixed results and odds after street food consumption varying from approximately 1.4 to 2.1 [15]. Protective measures while traveling were proven ineffective [35][37][43,54]. International travel, followed by travel to Asia, travel to India, antibiotic use while traveling, vegetarian diet, and street food consumption were identified as important variables.

4. Animal and Environmental Variables

Of the animal-related variables, pets and farming were investigated in reviews for increasing the odds of AMR E. coli amongst community-dwelling populations (Table 34). All reviews reporting on pet owners reported no increased odds of AMR E. coli. No statistical results were reported on farming. Amongst the types of farms, poultry in the Netherlands has been identified as a probable source of genetic AMR E. coli transmission in two reviews identified through whole-genome sequencing [38][39][47,49]. Looking at the environmental-related variables, swimming in freshwater doubled the risk of AMR E. coli infection in one systematic review [23][48] (Table 34). No variables were identified as important in both categories.
Table 34. Animal and environmental variables of E. coli AMR among community-dwelling populations.
Animal Subcategory Number of Studies Investigating

Variable (Number of Participants)
Magnitude of Association

OR (95% CI)
Importance of Rating *
Pets Pet owner 963 (5 studies) 1.39 ** (0.89–2.18) [24][40][44,46]
9403 (12 studies) 1.18 ** (0.83–1.68) [40][44]
5159 (4 studies) 1.15 (0.33–4.06) [15]
  Dog owner 9403 (12 studies) 0.88 ** (0.56–1.40) [40][44]
  Cat owner 9403 (12 studies) 1.16 ** (0.58–2.34) [40][44]
  Rodent owner 9403 (12 studies) 1.34 ** (0.43–4.18) [40][44]
NR (12 studies) 14.16 (5.50–36.45) [35][54]
370 (1 study) 30.0 (6.3–147.2) [36][45]
To Africa NR (3 studies)
  Bird owner 9403 (12 studies) 0.91 ** (0.38–2.18) 0.94 ** (0.14–6.17) [24][46]
23
]
[
48
]
0
Longer duration of course


(>7 days vs. <7 days amoxicillin and trimethoprim)
[40][ To India 182 (3 studies) 2.4 ** (1.26–4.58) [24][46] +
44 NR (3 studies) 3.80 (2.23–6.47) [15]
] Health while traveling Inflammatory bowel disease 5253 (20 studies) 2.09 (1.16–3.77) [37][43] 0
Diarrhea NR (4 studies) 1.65 (1.02–2.68) [15] +
5253 (20 studies) 1.69 (1.25–2.30) [37][43] 1521 (2 studies) 1.50 (0.76–2.92)
NR (12 studies) 2.02 (1.45–2.81) [35][54]
430 (1 study) 31.0 (2.7–358.1) [36][45]
Environment         Contact with healthcare while traveling 5253 (20 studies) 1.53 (1.09–2.15) [37][43] 0
Antibiotic use 5253 (20 studies) 2.38 (1.88–3.00) [37][43] + [26][42] 0
NR (12 studies) 2.78 (1.76–4.39) [35][54]
NR (4 studies) 2.81 (1.47–5.36) [15]
99 (1 study) 3.0 (1.4–6.7) [36][45]
99 (1 study)
Freshwater Swimming 290 (1 study) 2.1 (1.02–4.3) [23][48] 0 5.0 (1.1–26.2) [36][45]
Traveler demographics Backpackers compared to other travelers 5253 (20 studies) 1.46 (1.20–1.78) [37][43] 0
Vegetarian diet 5253 (20 studies) 1.41 (1.01–1.96) [37][43] + 1521 (2 studies) 2.89 (1.44–5.78) [26][42]
Multiple courses

(>3 courses vs. 1 course, trimethoprim, amoxicillin, trimethoprim)
1521 (2 studies) 0.4 (0.12–1.31) [26][
NR (3 studies) 42] ++
1.92 (1.13–3.26) [15] 1521 (2 studies) 3.95 (1.06–14.72) [
Diet associated with risk (pastry, meals from stalls, etc.) NR (12 studies) 1.27 (0.67–2.41) [35]26][42]
1521 (2 studies)
* Importance rating refers to the statistical significance of a potential variable and/or effect size estimate in relation to E. coli AMR; i.e., the amount of studies within the reviews that found statistically significant results with 0 weak association and – No association ** Risk ratio (95% CI) instead of odds ratio presented.

5. Temporal Relationship Variable and AMR E. coli

Eleven reviews investigated the temporal relation of variables and outcomes of AMR E. coli with antibiotic use and travel as subcategories (Table 45). Reviews showed that resistance after antibiotic use can persist for up to 12 months [15][26][41][15,39,42]. All cut-off points before one year were consistently associated with increasing the odds of AMR E. coli varying from 1.4 to 13.2. The risk of AMR E. coli after traveling abroad is highest in the first six weeks but decreases over time [37][43]. Six months [32][41][39,51] after antibiotic use was identified as the most important variable for AMR E. coli, followed by one and three months [32][41][42][38,39,51].
Table 45. Temporal relationship of variables for E. coli AMR among community-dwelling populations.
Variable Subcategory Number of Studies Investigating

Variable (Number of Participants)
Magnitude of Association

OR (95% CI)
Importance of Rating *
Time after

antibiotic use
One week 129 (2 studies) 7.1 (4.2–12) [25][35] 0
  Two weeks NR (6 studies) 1.08 (0.6–1.96) [42][38] +
NR (1 study) 6.12 (3.18–11.76) [41][39]
  One month NR (6 studies) 1.38 (1.16–1.64) [42][38] ++
93 (1 study) 1.8 (0.9–3.6) [25][35]
NR (1 study) 6.20 (2.14–15.96) [41][39]
NR (2 studies) 8.38 (2.84–24.77) [41][39]
1208 (3 studies) 11.21 (7.13–17.63) [32][51]
  Two months 14,348 (5 studies) 2.5 (2.1–2.9) [26][42] +
NR (1 study) 5.08 (2.70–9.56) [42
3.62 (1.25–10.48)
[
26
]
[
42
]
][38]
Mass administration
NR (1 study)
3.64 (2.38–5.78)
[
32
]
[
51
] +++
NR (5 studies) 7.8 (3.0–20.2) [27][52]
NR (5 studies) 10.2 (5.9–17.8) [27][52
 ]
NR (5 studies) 17.1 (2.3–127.7) [27][52]
Three months NR (6 studies) 1.65 (1.36–2.0) [42][38] ++
NR (1 study) 3.38 (2.05–5.55) [41][39]
1208 (3 studies) 10.64 (3.79–29.92) [32][51] [54
  Six months NR (1 study) 3.16 (1.65–6.06) [41][39] +++ ]
1208 (3 studies) 4.76 (1.52–14.90) [32][51]
NR (1 study) 13.23 (7.84–22.31) [41][39]
  12 months 11, 51, 54, 59, 60 14,348 (5 studies) 1.33 (1.2–1.5) [26][
42] +
NR (1 study) 0.94 (0.57–1.56) [41][39]
10,079 (13 studies) 1.84 (1.35–2.51) [15]
NR (1 study) 1.89 (1.04–3.42) [41][39] Street food consumption
  Over 12 months NR (1 study) 0.94 (0.57–1.56) [41][39]
Time after

return from travel
Six weeks 290 (1 study) 16.4 (3.4–78.8) [23][48] +
  Between six weeks and two years 290 (1 study) 2.2 (1.1–4.3) [23][48] 0 NR (2 studies) 0.92 (0.49–1.74) [15] +
NR (2 studies) 1.37 (1.08–1.73) [15]
NR (2 studies) 2.09 (1.30–3.38) [15]
  Raw vegetable consumption NR (2 studies) 0.34 (0.12–0.93) [15]
NR (2 studies) 0.58 (0.33–1.07) [15]
NR (2 studies) 2.18 (1.29–3.68) [15]
Protective measures while traveling Consuming bottled water 5253 (20 studies) 1.29 (0.50–3.34) [37][43] Higher dose

(each 200 mg trimethoprim tablet extra and 500 mg instead of 250 mg amoxicillin)
1521 (2 studies) 1.01 (1.01–1.02) [26][42]
General protective measures (disposable gloves, bottled water, etc.) NR (12 studies) 0.83 (0.61–1.13) [+
35][54] 1521 (2 studies) 2.26 (1.13–4.55) [26][42]
Meticulous hand hygiene 5253 (20 studies) 1.10 (0.81–1.49) Comorbidities Previous/recurrent UTI 7170 (1 study) 1.3 (1.01–1.6) [23][48] ++
408 (1 study) 3.4 (1.8–6.7) [23][48]
[37][43]
Probiotics 5253 (20 studies) 1.06 (0.78–1.45) [37][43] 510 (1 study) 3.8 (1.8–8.1) [23][48]
Previous/recurrent pyelonephritis 300 (1 study) 1.7 (0.7–3.9) [23][48]
Previous catheterization 408 (1 study) 3.3 (1.7–6.6) [23][48] +
Diarrhea symptoms 5144 (7 studies) 1.53 (1.27–1.84) [15] 0
Diabetes 300 (1 study) 1.7 (0.8–3.4) [23][48] ++
290 (1 study) 3.7 (1.1–12.7) [23][48]
484 (1 study) 3.0 (1.1–8.0) [23][48]
Recurrent acute pyelonephritis and a history of diabetes 300 (1 study) 4.2 (1.3–16.9) [23][48] +
Renal or urological disorder 7170 (1 study) 1.6 (1.0–2.5) [23][48]
484 (1 study) 3.5 (1.0–11.5) [23][48]
History prostatic disease 510 (1 study) 9.6 (2.1–44.8) [23][48] +
Chronic disease 2323 (3 studies) 0.91 (0.13–6.53) [15]
Medication use Immunosuppressive therapy 7170 (1 study) 1.5 (1.1–2.1) [23][48] 0
Corticosteroids 172 (1 study) 24.3 (2.4–246.9) [23][48] +
Acid suppressants 4111 (3 studies) 1.31 (0.11–15.5) [15] 0
NR (4 studies) 1.41 (1.07–1.87) [33][55]
Hospitalization Previous hospitalization 1379 (5 studies) 1.18 ** (0.78–1.81) [24][46] +
1163 (4 studies) 1.28 ** (0.82–2.03) [24][46]
7170 (1 study) 1.7 (1.3–2.3) [23][48]
172 (1 study) 2.9 (1.3–6.6) [23][48]
7170 (1 study) 3.9 (2.6–5.8) [23][48]
449 (1 study) 3.9 (1.2–12.7) [23][48]
Prior surgery 172 (1 study) 2.8 (1.9–8.0) [23][48] 0
Diet Vegetarian 6802 (5 studies) 1.60 (1.0043–2.5587) [15] 0
Raw milk 226 (1 study) 7.54 (2.41–23.45) [15] +
Fish 290 (1 study) 0.6 (0.5–0.9) [23][48] 0
Sex and age Older age 300 (1 study) 2.0 (1.02–3.5) [23][48] 0
Male sex NR (9 studies) 0.96 (0.74–1.24) [31][41] 0
7170 (1 study) 1.6 (1.2–2.1) [23][48]
* Importance rating refers to the statistical significance of a potential variable and/or effect size estimate in relation to E. coli AMR; i.e., the amount of studies within the reviews that found statistically significant results with +++ very strong association, ++ strong association, + moderate association, 0 weak association and – No association ** Risk ratio (95% CI) instead of odds ratio presented.

2.2. Comorbidities, Medication Use, and Hospitalization

Urogenital comorbidities increased the odds of AMR E. coli, as did some non-urogenital conditions (Table 12), with the most important variables being previous/recurrent urinary tract infection (UTI) [23][48] and diabetes [23][48]. There were mixed results for variables indicating increased vulnerability, with a positive association for previous hospitalization [24][46] and corticosteroid use [23][48], mixed results for acid suppressants [15][33][15,55], and no association for increased odds of AMR E. coli in those with chronic disease [15] or renal and urological disorders [23][48].

2.3. Diet, Sex, Age, and Living

Vegetarian diet, older age (>55 years) [23][48], and children attending day-care [31][41] increased the odds of AMR E. coli varying from 1.5 to 2.0 (Table 12). Raw milk [15] and lower socioeconomic status [34] were found to be the most important variables in this category. A weekly fish meal and living in Northern Europe compared to Southern Europe were found to reduce the risk of infection of AMR E. coli
* Importance rating refers to the statistical significance of a potential variable and/or effect size estimate in relation to E. coli AMR; i.e., the amount of studies within the reviews that found statistically significant results with +++ very strong association, ++ strong association, + moderate association, 0 weak association and – No association ** Risk ratio (95% CI) instead of odds ratio presented.

3. Travel

The last human-related variable was travel, with destination, health while traveling, traveler demographics, protective measures, and household transmission as subcategories (Table 23). International travel [23][24][46,48] increased the odds of AMR E. coli, with Asia [15][35][36][15,45,54] and India [15][24][15,46] as travel destinations having the highest risks and were found to be the most important variables in this category. Reviews reporting on bowel-related diseases while traveling reported a positive association with odds for AMR E. coli ranging from 1.6 [15] to 31 [36][45]. Antibiotic use while traveling showed a positive association in all reviews, increasing odds from 2.4 [37][43] to 5 [36][45]. There were no conclusive results around food consumption while traveling on the odds of AMR E. coli, with a vegetarian diet increasing the odds by 1.4 [37][43]
* Importance rating refers to the statistical significance of a potential variable and/or effect size estimate in relation to E. coli AMR; i.e., the amount of studies within the reviews that found statistically significant results with +++ very strong association, ++ strong association, + moderate association, 0 weak association and – No association.