Risk factors associated with prolonged intestinal colonization of ESBL-producing Enterobacteriaceae – a prospective cohort study

Figures & data

Table 1 Baseline characteristics of the study population based on medical records and questionnaires

Baseline characteristic	EPE-positive (n=81)	EPE-negative (n=62)
Age, median years (range)	69 (19–87)	66 (31–86)
Female sex (%)	51 (63)	41 (66)
Original culture positive for EPE, source (%)
Urine	66 (81)	40 (65)
Blood^1	7 (9)	3 (5)
Rectal	8 (10)	19 (30)
Duration of known carriage, median months (range)	7 (3–108)	8 (3–56)
History of any EPE infection (%)
Yes	72 (89)	44 (71)
No, ie, colonization	9 (11)	18 (29)
EPE infection and/or colonization prior to January 2016 (%)	14 (17)	6 (10)
Urological intervention within 6 months^2 (%)	29 (36)	7 (11)
Inflammatory bowel disease (%)	0 (0)	2 (3)
Inpatient hospital care within 2 years^3 (%)	44 (54)	26 (42)
Urinary catheter or clean intermittent catheterization (%)	9 (11)	2 (3)
Antibiotic treatment within 2 years^4 (%)	69 (85)	53 (85)
Overall medications (%)
No medication	14 (17)	13 (21)
1 or 2 medications	15 (19)	19 (31)
3 or more medications	52 (64)	30 (48)
Ongoing proton pump inhibitor treatment (%)	18 (22)	11 (18)
Ongoing immunosuppressive treatment^5 (%)	4 (5)	3 (5)

Notes: All data were collected at the time of inclusion, ie, when fecal culture was obtained. ¹If positive in both blood and urine, only blood was chosen. ²Minor or major invasive procedure on bladder, prostate and/or kidney and cystoscopy. ³In Sweden and/or internationally. ⁴Any systemic antibiotic. ⁵Including any dosage of corticosteroids and/or methotrexate. All percentages are rounded up to the nearest integer.

Abbreviations: ESBL, extended spectrum β-lactamase; EPE, extended spectrum β-lactamase producing Enterobacteriaceae.

Table 2 Univariate statistic model of putative risk factors for prolonged intestinal EPE carriage using Fisher’s exact test

Variable	EPE-positive (n=76)	EPE-negative (n=67)	P-value
Age >70 years	32	19	0.115
Female sex	50	45	1.000
Escherichia coli^1	73	61	0.149
ESBL phenotype A^1	71	60	0.229
Bacteria resistant to Ciprofloxacin and/or Trimethoprim/Sulfamethoxazole^1	62	51	0.538
Isolate in urine^1	57	36	0.009
History of EPE infection	60	40	0.007
Carriage prior to January 2016	12	6	0.218
Urological intervention within 6 months^2	26	6	0.000
Inflammatory bowel disease	0	2	0.218
Charlson comorbidity index >0	39	26	0.131
Inpatient hospital care within 2 years^3	37	29	0.506
Urinary catheter or clean intermittent catheterization	7	1	0.066
Antibiotic use within 2 years^4	60	52	1.000
Overall drug treatment >0	57	53	0.699
Proton pump inhibitor treatment	15	12	0.831
Immunosuppressive treatment^5	3	3	1.000
Travel to Africa and/or Asia within 2 years#	15	26	0.020
Abdominal pain and/or altered bowel habits#	23	27	0.358
Domestic animal#	20	22	0.570
Currently working#	22	24	0.454
>1 person in household#	50	42	0.275
Known carrier of EPE in household^6#	2	2	1.000
Vegetarian#	1	0	1.000
Post-secondary education#	33	32	1.000

Notes: Statistical analysis using Fisher’s exact test with exact 2-sided significance. A P-value of ≤0.05 was considered significant. All data were collected originating at time of inclusion, ie, when fecal culture was collected, except ¹ which denotes original EPE-positive culture. ²Minor or major invasive procedure on bladder, prostate and/or kidney and cystoscopy. ³Both in Sweden and internationally. ⁴Any systemic antibiotic. ⁵Including any dosage of corticosteroids or methotrexate. ⁶Other than patient included in the study. All calculations are based on the weighted data. All counts are rounded to the nearest integer. Due to rounding, there are small variations in the number of patients included in each test. All percentages are rounded up to the nearest integer. #Based on the total number of questionnaire responses according to Table S3. In this article, a P-value of ≤0.05 highlighted in bold was considered significant. 

Abbreviations: ESBL, extended spectrum β-lactamase; EPE, extended spectrum β-lactamase producing Enterobacteriaceae.

Table 3 Multiple logistic regression model of putative risk factors for prolonged intestinal EPE carriage

Variable	EPE-positive (n=62)	EPE-negative (n=58)	OR	CI 95%		P-value
				Lower	Upper
Age ≥70 years	27	18	1.19	0.43	3.27	0.957
Female sex	45	38	2.57	0.82	8.07	0.089
Antibiotic resistance^1						0.180
Ciprofloxacin	15	9	1.54	0.35	6.71	0.341
Trimethoprim/sulfamethoxazole	11	16	0.55	0.15	2.07	0.714
Ciprofloxacin + trimethoprim/sulfamethoxazole	25	23	1.88	0.55	6.40	0.124
History of EPE infection	52	35	4.12	1.36	12.51	0.002
Urological intervention within 6 months^2	23	5	4.53	1.43	14.38	0.005
Urinary catheter or intermittent clean catheterization^#	5	1	2.10	0.23	19.15	0.544
Overall medications^#						0.089
1–2 medicines	11	19	0.19	0.05	0.77	0.028
3 or more medicines	36	27	0.31	0.09	1.06	0.145
Travel to Africa and/or Asia within 2 years^#	15	26	0.40	0.15	1.04	0.100

Notes: Statistical analysis using binary logistic regression model. P-value ≤0.05 was considered significant. Odds ratio for prolonged intestinal EPE carriage. All data were collected originating at the time of inclusion, ie, when fecal culture was collected, except ¹ which denotes original EPE-positive culture. ²Minor or major invasive procedure on bladder, prostate and/or kidney and cystoscopy. All calculations are based on the weighted data. All counts are rounded to the nearest integer. Due to missing data, the regression was calculated on 120 observations. All percentages are rounded up to the nearest integer. ^#Information based on questionnaires. In this article, a P-value of ≤0.05 highlighted in bold was considered significant. 

Abbreviations: OR, odds ratio; CI, confidence interval; ESBL, extended spectrum β-lactamase; EPE, extended spectrum β-lactamase producing Enterobacteriaceae.

Table 4 Stepwise forward multiple regression model of potential risk factors for prolonged intestinal EPE carriage

Step	Variable	OR	CI 95%		P-value
			Lower	Upper
Step 1	Urological intervention within 6 months^1	5.72	2.05	15.92	0.001
Step 2	Urological intervention within 6 months	4.69	1.65	13.33	0.004
	History of EPE infection	2.77	1.13	6.83	0.027
Step 3	Urological intervention within 6 months	4.32	1.50	12.42	0.007
	History of EPE infection	2.82	1.12	7.10	0.028
	Travel to Africa and/or Asia within 2 years^#	0.42	0.18	0.96	0.040

Notes: Statistical analysis using binary logistic regression model. P-value ≤0.05 was considered significant. Odds ratio for prolonged intestinal EPE carriage. All data were collected originating at the time of inclusion, ie, when fecal culture was collected. ¹Minor or major invasive procedure on bladder, prostate and/or kidney and cystoscopy. All calculations are based on the weighted data. All counts are rounded to the nearest integer. Due to missing data, the regression was calculated on 120 observations. Included variables in the stepwise regression model as presented in Table 3. ^#Information based on questionnaires. In this article, a P-value of ≤0.05 highlighted in bold was considered significant. 

Abbreviations: OR, odds ratio; CI, confidence interval; EPE, Extended spectrum β-lactamase producing Enterobacteriaceae.

Figure 1 Flow chart of study patient inclusion and questionnaire distribution.

Abbreviation: EPE, extended spectrum β-lactamase producing Enterobacteriaceae.