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Accepted Manuscript

Clinical risk scoring system for predicting extended-spectrum -lactamase-producing


Escherichia coli infection in hospitalized patients
K. Kengkla, N. Charoensuk, M. Chaichana, S. Puangjan, T. Rattanapornsompong, J.
Choorassamee, P. Wilairat, S. Saokaew
PII:

S0195-6701(16)00054-2

DOI:

10.1016/j.jhin.2016.01.007

Reference:

YJHIN 4726

To appear in:

Journal of Hospital Infection

Received Date: 21 August 2015


Accepted Date: 12 January 2016

Please cite this article as: Kengkla K, Charoensuk N, Chaichana M, Puangjan S, Rattanapornsompong
T, Choorassamee J, Wilairat P, Saokaew S, Clinical risk scoring system for predicting extendedspectrum -lactamase-producing Escherichia coli infection in hospitalized patients, Journal of Hospital
Infection (2016), doi: 10.1016/j.jhin.2016.01.007.
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ACCEPTED MANUSCRIPT
K. Kengkla et al.
Clinical risk scoring system for predicting extended-spectrum -lactamase-producing
Escherichia coli infection in hospitalized patients
K. Kengklaa,b, N. Charoensuka, M. Chaichanaa, S. Puangjana, T. Rattanapornsomponga, J.
a

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Choorassameea,b, P. Wilairata,b, S. Saokaewa,b,*


School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand

Center of Health Outcomes Research and Therapeutic Safety (Cohorts), School of

Pharmaceutical Sciences, University of Phayao, Phayao, Thailand


____________________

Corresponding author. Address: Center of Health Outcomes Research and Therapeutic Safety

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(Cohorts), School of Pharmaceutical Sciences, University of Phayao, Phayao, 56000 Thailand.

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Tel: +66 (0)5446 6666; fax: +66 (0)5446 6661.


E-mail address: saokaew@gmail.com (S. Saokaew).
SUMMARY

Background: Extended spectrum -lactamase-producing Escherichia coli (ESBL-EC) has


important implications for infection control and empiric antibiotic prescribing. This study aims to
develop a risk scoring system for predicting ESBL-EC infection based on local epidemiology.

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Methods: The study retrospectively collected eligible patients with a positive culture for E. coli
during 2011 to 2014. The risk scoring system was developed using variables independently
associated with ESBL-EC infection through logistic regression-based prediction. Area under the

of the model.

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receiveroperator characteristic curve (AuROC) was determined to confirm the prediction power

Findings: Predictors for ESBL-EC infection were male gender [odds ratio (OR): 1.53], age 55

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years (OR: 1.50), healthcare-associated infection (OR: 3.21), hospital-acquired infection (OR:
2.28), sepsis (OR: 1.79), prolonged hospitalization (OR: 1.88), history of ESBL infection within
one year (OR: 7.88), prior use of broad-spectrum cephalosporins within three months (OR:
12.92), and prior use of other antibiotics within three months (OR: 2.14). Points scored ranged
from 0 to 47, and were divided into three groups based on diagnostic performance parameters:
low risk (score: 08; 44.57%), moderate risk (score: 911; 21.85%) and high risk (score: 12;
33.58%). The model displayed moderate power of prediction (AuROC: 0.773; 95% confidence
interval: 0.7420.805) and good calibration (HosmerLemeshow 2 = 13.29; P = 0.065).
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Conclusion: This tool may optimize the prescribing of empirical antibiotic therapy, minimize
time to identify patients, and prevent spreading of ESBL-EC. Prior to adoption into routine
clinical practice, further validation study of the tool is needed.
Keywords:

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Clinical prediction rule


Escherichia coli
Extended-spectrum -lactamase
Risk scoring system
Introduction

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Multidrug-resistant (MDR) pathogens cause hospital-acquired, healthcare-associated and


community-acquired infections; one such pathogen is extended-spectrum -lactamase-producing

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Escherichia coli (ESBL-EC), which has now spread across all regions of the world, including
Thailand.13 These infections increase morbidity, mortality, length of stay, and treatment-related
costs in seriously infected patients.46

It is generally recommended that broad-spectrum antibiotics should be used as empiric


therapy in patients at risk of infection with ESBL-producing bacteria.7 Several studies suggest
that carbapenems are the drugs of choice for serious infections with these bacteria.8 However,

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over-use of carbapenems for empirical treatment of suspected ESBL-EC infection may promote
carbapenem-resistant bacteria such as E. coli, Acinetobacter baumannii, and Pseudomonas
aeruginosa, as well as adding to antibiotic costs.7,9 This needs to be balanced against the risks of
delay in initiating appropriate antibiotic therapy in hospitalized cases of infection with ESBL-EC,

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which may be associated with increased rates of complications and mortality.5,10,11


Accurate determination of risk factors for ESBL-EC infection may assist in targeting

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empirical carbapenem therapy. Thus, treatment failure, infectious complications, antibiotic costs,
and the risk of selecting carbapenem-resistant bacteria should decline.1214 A risk discrimination
tool that can identify patients likely to have ESBL-EC might therefore assist with rational
antibiotic prescribing and the early implementation of infection control precautions.
A previously published clinical prediction scoring tool was reported to display good

discrimination and excellent predictive value for both community- and hospital-acquired
infections with ESBL-producing Enterobacteriaceae.15,16 When we applied these scoring systems
on our patients, only two factors predicting possession of ESBL-EC remained: previous
hospitalization and recent antibiotic therapy with -lactam/-lactamase inhibitors. Both the model

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of Tumbarello et al. and the Duke Model had poor predictive values, with area under the
receiveroperator characteristic curve (AuROC) of 0.530 and 0.548, respectively.15,16 This may
be because the epidemiology and phenotypic determinants of different bacteria vary between
geographical areas, and even between institutions in the same geographical area.17,18

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Therefore, this study was intended to develop a reliable, easy-to-use risk scoring system
to predict ESBL-EC infection based on local epidemiology in Thailand, with the aim of
improving carbapenem antibiotic stewardship.
Methods
Patients

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Phayao hospital is a 400-bed secondary care medical centre located in the north of

Thailand. All patients who had positive cultures for E. coli in any specimen, and who were

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admitted to hospital from January 2011 to December 2014, were eligible for inclusion. Patients
readmitted to hospital within 30 days were excluded, but those readmitted after more than 30
days were included. Patients with missing data on the electronic database were excluded. Patients
were classified into two groups: ESBL-EC (case) and non-ESBL-EC (control).
Definitions

Hospital-acquired infection (HAI) was defined as an infection that occurred >48 h after

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admission to the hospital.19 Healthcare-associated infection (HCAI) was defined as an infection


that occurred within 48 h of admission with more than one of the following criteria: (i) was
receiving intravenous therapy at home; (ii) had attended a hospital or haemodialysis clinic, or
received intravenous chemotherapy, in the preceding 30 days; (iii) had been hospitalized for two

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or more days within 90 days before onset of the infection; (iv) resident in a nursing home or longterm care facility.20 Community-acquired infection (CAI) was defined as an infection that was

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present on admission to hospital, or that occurred within 48 h of admission, where the criteria for
HCAI were not fulfilled.19

Sepsis was defined as the systemic inflammatory response to infections (SIRs),

manifested by two or more of temperature >38 or <36C, heart rate >90 bpm, respiratory rate
>20 bpm or PaCO2 <32 mmHg, and white blood cell count >12,000 or <4000 cells/mm3 in a
patient with suspected infection.21,22
Predictor parameters
Clinical characteristics, medical histories, and drug exposures were obtained from the
computerized medical database. Parameters of interest included age, gender, types of infection
(HAI, HCAI, or CAI), hospital location at time of infection (general ward, surgical ward, and

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intensive care unit), sepsis, previous history of E. coli infection, history of ESBL-EC infection
within the preceding year, hospital stays before infection, interventions (recent surgery,
percutaneous drainage, peritoneal dialysis, Foley catheter, mechanical ventilator, and nasogastric
tube), comorbidities (diabetes mellitus, cardiovascular diseases, neurological diseases, pulmonary

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diseases, hepatobiliary diseases, chronic kidney disease, acute kidney injury, solid tumour cancer,
and autoimmune diseases), medication history (corticosteroids and other immunosuppressive
agents), and antibiotic exposures in the preceding three months.
Data analysis

Descriptive statistics on study variables are presented as median (range or interquartile

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range), mean (SD), or frequency count (percentage), as appropriate. The associations between
candidate risk factors and ESBL infection were analysed using logistic regression with variance-

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corrected model and summarized with odds ratios (ORs) and 95% confidence intervals (CIs).
Each factor was screened for an association with ESBL infection via univariate logistic
regression; those with 0.1 were carried forward in multivariate analyses. Candidate risk
factors were then plugged into a multivariate logistic regression using a cluster-robust variancecorrected model with backward elimination. We removed variables with P > 0.05. Odds ratio and
95% CI were calculated to evaluate the strength of any association that emerged. Any variable

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with P < 0.05 was retained in the final model. A points-based system was developed by
coefficient from the final regression model. The coefficient regression of each variable was then
divided by the smallest coefficient number and rounded to the nearest integer. The prediction
model performed discriminatory power by AuROC and the calibration efficiency was tested

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using the HosmerLemeshow test. Potential interactions were also checked in the predictive
model. Collected data were processed using Stata, version 12.1 (StataCorp., College Station, TX,

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USA).

This study was approved by the Research Ethics Committee of the Division of Research

Administration and Educational Quality Assurance, University of Phayao, Phayao, Thailand (No.
5702010001).
Results

Of the 3159 patients with positive cultures for E. coli assessed for eligibility, 810 were
finally included in the study: 443 patients in the ESBL-EC group (cases) and 367the patients in
non-ESBL-EC group (controls) (Figure 1). The majority of patients were female 456 (56.30%)
and mean age (SD) was 63.32 (19.12) years. There were 446 (55.0%) urinary tract infections, 100

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(12.3%) lower respiratory infections, 85 (10.5%) abdominal infections, 56 (6.9%) skin infections,
and 20 (2.5%) bloodstream infections.
Patients with ESBL-EC and non-ESBL-EC infection are summarized by univariate
analysis in Table I. The patients with ESBL-EC infection were older, a higher proportion was

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male, and there were significant associations with hepatic insufficiency, presence of sepsis, recent
ESBL infection within one year, recent surgery, mechanical ventilator, prolonged hospitalization
(>7 days), and prior use of broad spectrum cephalosporins and fluoroquinolones.
Significant predictors

Significant (P < 0.05) multivariate predictors for ESBL-EC infection were male sex (OR:

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1.53; 95% CI: 1.112.12), age 55 years (1.50; 1.042.16), HCAI (3.21; 2.114.88), HAI (2.28;
1.483.50), sepsis (1.79; 1.292.49), prolonged hospitalization (1.88; 1.093.23), history of

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ESBL-EC infection within one year (7.88; 2.2427.68), prior use of broad-spectrum
cephalosporins (12.92; 4.4237.78), and prior use of other antibiotics (2.14; 1.443.20).
Scoring system

The scores were divided by significant coefficient predictors with the smallest coefficient
(0.40) then rounded to the nearest integer. The scores ranged from 0 to 13. Each score was
summed to overall ESBL infection risk scores, which could range from 0 to 47 (Table II).

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Discrimination

The average ESBL infection risk scores in case and control groups were 12.85 7.02 and
6.86 4.38, respectively (P < 0.001) (Figure 2, Table III).
The scores discriminated patients with ESBL-EC infection from those with non-ESBL-

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EC infection with moderate-level validity (AuROC 0.773, 95% CI 0.7420.805) in a wellcalibrated predictive model (HosmerLemeshow 2 = 13.29; P = 0.065).

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Clinical predictions

The risk scoring system was developed as a clinical prediction rule by determining the

cut-off according to the discrimination plot and performance of diagnostic parameters in order to
identify patients at probability risk of ESBL-EC infection (Table IV).
We considered and selected two cut-off points. A cut-off score of 9 had good sensitivity

(74%) and moderate specificity (66%); positive predictive value (PPV) and negative predictive
value (NPV) were 73% and 68%, respectively, and accuracy (70%) was acceptable. With a cutoff score of 12, the sensitivity declined (53%), but specificity rose considerably (90%). NPV
and PPV were 61% and 86%, respectively, and overall accuracy (69%) was comparable with that
of the lower cut-off value (Table IV).

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ESBL infection scores were classified into three risk levels. Low risk level was defined as
overall scores of 8 points (N = 361, 44.57%), moderate risk as scores of 911 points (N = 177,
21.85%), and high risk as scores of 12 points (N = 272, 33.58%). Using this scoring system, 244
of 810 (30.12%) cases with E. coli were correctly classified as low risk (score 08), with 117

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(14.44%) cases misclassified (risk underestimated). At the moderate risk level (score 911), the
score correctly identified 93 of 810 (11.48%) cases; however, 84 (10.38%) moderate risk level
cases did not have ESBL-EC. At the high risk levels (score 12), the score correctly classified
233 of the 810 (28.77%) cases; only 39 (4.81%) cases were misclassified (risk overestimated)

having ESBL-EC infection using this scoring tool.


Discussion

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(Table III). Overall, 70.37% of patients were correctly classified as being at risk or not at risk of

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In this study, we established the first clinical risk scoring system for predicting ESBL-EC
infection in Asia using clinical and demographic variables at time of infection. Patients were
classified into one of three groups of likelihood of having ESBL-EC (Figure 3) with acceptable
performance (AuROC: 0.773).23 The tool may therefore be clinically useful in clinical decisionmaking for hospitalized patients. Whereas predictive scores have been developed in previous
research for predicting ESBL-EKP infection in the community or in hospital , our study included

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all types of infection (HAI, HCAI, and CAI).15,16

Our predictive model consists of the nine predictors of ESBL-EC infection. At least three
of these (age >55 years, and exposure to broad-spectrum cephalosporins and other antibiotics
within three months) are consistent with predictors in previous models.15,16 Additionally, we

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found that male gender, HCAI, HAI, prolonged hospitalization, sepsis, and ESBL-EC infection
within one year were new predictors of ESBL-EC. However, in contrast to Charlsons

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comorbidity index, recent urinary catheterization and immunosuppression were not predictors in
our study.15,16 We also noted that Charlsons comorbidity index score was not simple and
convenient to use in clinical practice.
Both c-statistics of the model and goodness-of-fit by the HosmerLemeshow 2-statistic

confirmed a good discriminatory power of the AuROC, although the overall performance of our
model was poorer than in both previous predictive models.15,16 However, our model appears to be
the best available for identifying patients at risk of having infection with ESBL-EC.24
Using our model, if the intention were to screen hospitalized patients to determine the
likelihood of infection with ESBL-EC, a cut-off point with high sensitivity and low specificity
could be employed. On the other hand, if application were intended to guide therapeutic

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intervention (in particular to avoid overuse of carbapenems), then a cut-off model point with a
lower sensitivity and higher specificity would be appropriate.25 In the model of Tumbarello et al.
the cut-off of at least 3 points had a very high sensitivity (93%) and NPV (97%), but very low
specificity (62%) and PPV (45%).15 By raising the cut-off to 6 points, sensitivity and NPV fell to

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63% and 88%, but specificity and PPV increased to 95% and 80%. In the Duke model, with a
cut-off of 8 points, good specificity and PPV (95% and 79%, respectively) contrasted with
poorer sensitivity (58%).16

In our study, the cut-off was based on assessment of sensitivity, specificity, PPV, NPV
and accuracy. The best cut-off points for predicting any risk of ESBL-EC infection was 9

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points, which had an accuracy of 70% and acceptable underestimation at about 14%. However,
this cut-off had moderate sensitivity (74%) and NPV (68%) and inadequate specificity, including

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overestimation at 15%. For this reason it is not the best cut-off point for predicting high risk of
ESBL-EC infection, nor for making empiric antibiotic prescribing decisions. Here, a cut-off point
with a higher specificity and PPV is required. We used a cut-off score for separating high from
moderate risk of ESBL-EC infection of 12 points. Specificity and PPV are increased to 89% and
86%, but sensitivity is lower at 53%.

We propose that cut-off scores may be used to classify patients into three groups with

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respect to empiric antibiotic therapy decisions. Patients with score of 8 are low risk, and do not
require empiric therapy to cover ESBL-EC. Patients with score of 911 are moderate risk (RR:
1.73; 95% CI: 1.362.20; P < 0.001]. We recommend the use of agents such -lactam/lactamase inhibitors or fluoroquinolones as empiric therapy for this group. Finally, patients with

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score 12 are defined as high risk (RR: 4.83; 95% CI: 3.586.53; P < 0.001], and for these we
recommend empiric therapy with a carbapenem.

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Our study has important limitations. First, we collected data only on patients with E. coli
infection, and we do not know whether the predictive score applies to other ESBL-producing
Enterobacteriaceae (e.g. Klebsiella pneumonia, Proteus mirabilis). Second, we collected data
from electronic medical charts retrospectively; it is likely that some of these data were
incomplete or inaccurate, especially information on previous admissions to other hospitals and
antibiotic histories. We recommended conducting a prospective study, reviewing fuller data sets,
and interviewing patients instead. Third, the predictive score was not validated due to an
inadequate sample size; full validation would be required before adoption of a scoring system
into clinical practice. Finally, our study was a single-centre retrospective study, and the findings
may not be generalizable, even within Thailand or South East Asia.

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In conclusion, a novel scoring system was developed for predicting ESBL-EC infection
that could certainly identify patients with these infections. The scores depended on nine
predictors, most of which are easy and convenient to ascertain; however, we do acknowledge that
accurate information about hospitalization in other hospitals and on previous antibiotic therapy

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may be difficult to obtain. Nevertheless, we believe that predictive tools such as ours may
improve the effectiveness of medical care, by allowing early targeting of interventions for

patients at risk of ESBL-producing bacteria. Thus, improvements in antibiotic prescribing and in


infection control can be achieved. We suggest that tools such as ours urgently need to be

developed, validated, and introduced into clinical practice as a key part of our fight against MDR

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Gram-negative bacteria.
Acknowledgements

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The authors wish to thank the authorities of the Phayao hospitals for their support. We
thank Prof. G.M. Oderda for reviewing the manuscript before submission.
Conflict of interest statement
None declared.
Funding sources

The study was partially funded by a grant from School of Pharmaceutical Sciences, University

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Table I
Distribution of candidate variable for extended-spectrum -lactamase (ESBL) Escherichia coli infection
ESBL

Non-ESBL

E. coli

E. coli

(N = 443)

(N = 367)

64.35 (17.30)

95% CI

62.28 (20.94)

1.01

0.991.01

0.134

344 (77.65%)

258 (70.30%)

1.47

1.062.04

0.023

213 (48.08%)

141 (38.42%)

1.48

1.102.00

Community-acquired

131 (29.57%)

233 (63.49%)

1.00

Reference

Healthcare-associated

179 (40.41%)

77 (20.98%)

4.13

2.925.85

<0.001

Hospital-acquired

133 (30.02%)

57 (15.53%)

4.15

2.875.99

<0.001

General ward

298 (67.27%)

280 (76.29%)

1.00

Reference

Intensive care unit

26 (5.87%)

11 (3.00%)

2.22

1.074.61

0.032

Surgical ward

119 (26.86%)

76 (20.71%)

1.47

1.042.08

0.029

Prolonged hospitalization (>7 days)

87 (19.64%)

28 (7.63%)

2.96

1.884.67

<0.001

Presence of sepsis

292 (65.91%)

203 (55.31%)

1.56

1.172.09

0.003

History of ESBL infection within 1 year

50 (11.29%)

11.55

3.9433.80

<0.001

55 years
Male sex

4 (1.09%)

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Intervention history

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Hospital location at time of infection

0.010

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Types of infection

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Age, mean years (SD)

P-value

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OR

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Characteristics

Recent surgery

132 (29.80%)

72 (19.62%)

1.74

1.242.43

0.001

Foley catheter

196 (44.24%)

148 (40.33%)

1.17

0.881.57

0.281

Mechanical ventilator

77 (17.38%)

44 (11.99%)

1.54

1.032.31

0.034

Comorbid conditions and medication history


Diabetes mellitus

101 (22.80%)

67 (18.26%)

1.32

0.921.91

0.136

Cardiovascular diseases

66 (14.90%)

45 (12.26%)

1.25

0.821.91

0.292
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OR

95% CI

E. coli

E. coli

(N = 443)

(N = 367)

Neurological diseases

52 (11.74%)

Pulmonary diseases

38 (10.35%)

1.15

0.731.81

0.540

61 (13.77%)

39 (10.63%)

1.34

0.842.14

0.217

Hepatic insufficiency

22 (4.97%)

31 (8.45%)

0.57

0.321.01

0.055

Chronic kidney diseases

83 (18.74%)

52 (14.17%)

1.40

0.952.06

0.091

Systemic corticosteroid therapy

29 (6.55%)

21 (5.72%)

1.15

0.642.09

Immunosuppressive therapy

4 (0.90%)

8 (2.18%)

0.41

0.121.44

Prior use of specific antibiotics within 3 months

P-value

RI
PT

Non-ESBL

SC

ESBL

0.637

0.164

M
AN
U

Characteristics

39 (8.80%)

25 (6.81%)

1.32

0.772.25

0.308

Narrow spectrum cephalosporins

13 (2.93%)

9 (2.45%)

1.20

0.502.90

0.681

Broad-spectrum cephalosporins

76 (17.16%)

16 (4.36%)

4.54

2.597.96

<0.001

-Lactam/-lactamase inhibitors

30 (6.77%)

14 (3.81%)

1.83

0.943.57

0.076

Carbapenems

8 (1.81%)

2 (0.54%)

3.36

0.6816.58

0.137

Aminoglycosides

5 (1.13%)

1 (0.27%)

4.18

0.4538.47

0.207

Fluoroquinolones

66 (14.90%)

34 (9.26%)

1.71

1.112.65

0.016

Co-trimoxazole

5 (1.13%)

5 (1.36%)

0.83

0.242.88

0.765

EP

OR, odds ratio; CI, confidence interval.

TE
D

Penicillins

AC
C

Odds ratio from univariate logistic regression analysis with variance corrected for 728 clusters in patient number.

ACCEPTED MANUSCRIPT

Table II
Significant predictors and assigned item score

Types of infection

Presence of sepsis
a

Prolonged hospitalization

History of ESBL E. coli infection within 1 year

1.53

Female

Reference

55 years

1.50

<55 years

Reference

Healthcare

Recent use of antibiotics

Coefficient

Score

1.112.12

0.010

1.042.16

0.030

3.21

2.114.88

<0.001

1.17

Hospital

2.28

1.483.50

<0.001

0.82

Community

Reference

Yes

1.79

No

Reference

Yes

1.88

No

Reference

Yes

7.88

No
c

P-value

0.40

1.292.49

0.001

0.58

1.093.23

0.023

0.63

2.2427.68

0.001

2.06

10

12.92

4.4237.78

<0.001

2.56

13

2.14

1.443.20

<0.001

0.76

Reference

BCEP

EP

Otherd
No

0.43

SC

Age

Male

95% CI

M
AN
U

Gender

OR

RI
PT

Category

TE
D

Predictors

Reference

AC
C

OR, odds ratio; CI, confidence interval; ESBL, extended-spectrum -lactamase; BCEP, broad-spectrum cephalosporin.
Coefficients and odds ratio from multivariate logistic regression analysis with variance corrected for 728 clusters in patient number.
a

Hospitalization more than seven days.

b
c

Hospitalization within one year.

Hospitalization within three months.

Other antibiotics (except broad-spectrum cephalosporin).

ACCEPTED MANUSCRIPT

Table III
Classification of cases versus controls into low, moderate, and high probability categories and risk-estimation validity
Cases

Control

range

(N = 443)

(N = 367)

Mean SD

12.85 7.02

6.86 4.38

Median (IQR)

6 (410)

12 (816)

Risk-estimation validitya
Over

Correct

Under

(%)

(%)

(%)

08

117 (26.41%)

244 (66.49%)

30.12

14.44

Moderate

911

93 (20.99%)

84 (22.89%)

10.38

11.48

High

12

233 (52.60%)

39 (10.63%)

4.81

28.77

Total

15.19

70.37

14.44

IQR, interquartile range.

EP

TE
D

Percentage of total patients.

AC
C

M
AN
U

Low

RI
PT

Score

SC

Categories

ACCEPTED MANUSCRIPT

Table IV

FP

TN

FN

Se (%)

Sp (%)

PPV (%)

NPV (%)

Acc (%)

442

359

99.77

2.18

55.18

88.89

55.56

442

359

99.77

2.18

55.18

88.89

55.56

421

299

68

22

95.03

18.53

58.47

75.56

60.37

415

277

90

28

93.68

24.52

59.97

76.27

62.35

407

255

112

36

91.87

30.52

61.48

75.68

64.07

366

187

180

77

82.62

49.05

66.18

70.04

67.41

358

173

194

85

80.81

52.86

67.42

69.53

68.15

341

142

225

102

76.98

61.31

70.60

68.81

69.88

326

123

244

117

73.59

66.49

72.61

67.59

70.37

10

300

101

266

143

67.72

72.48

74.81

65.04

69.88

11

278

85

282

165

62.75

76.84

76.58

63.09

69.14

12

233

39

328

210

52.60

89.37

85.66

60.97

69.26

13

211

30

337

232

47.63

91.83

87.55

59.23

67.65

14

173

18

349

270

39.05

95.10

90.58

56.38

64.44

15

146

12

355

297

32.96

96.73

92.41

54.45

61.85

16

117

359

326

26.41

97.82

93.60

52.41

58.77

17

98

360

345

22.12

98.09

93.33

51.06

56.54

SC

TP

AC
C

EP

TE
D

M
AN
U

Score

RI
PT

Distribution of score with diagnostic cut-off performance

TP, true positive; FP, false positive; FN, false negative; TN, true negative; Se, sensitivity; Sp, specificity; PPV, positive predictive value; NPV, negative predictive
value; Acc, accuracy.

ACCEPTED MANUSCRIPT
Figure 1. Selection of study patients.
Figure 2. Discrimination of extended-spectrum -lactamase (ESBL) Escherichia coli infection
based on ESBL infection risk scores. Dark grey bars: cases (N = 443); light grey bars: controls (N
= 367).

RI
PT

Figure 3. Distribution of extended-spectrum -lactamase infection risk level. Dark grey bars:

AC
C

EP

TE
D

M
AN
U

SC

infection; light grey bars: non-infection.

16

ACCEPTED MANUSCRIPT
Patients with E.coli infection in Phayao hospital from January 2011
to December 2014 were enrolled (n=3,159)

Excluded
- 277 unavailable data
in electronic database
- 213 duplicate isolate
Study patients
443 cases included for analysis

RI
PT

Control (n=2,226)
Patients with non-ESBL producing E.coli
-ESBL-E.coli

Case (n=933)
Patients with ESBL producing E.coli

Excluded
- 1,658 unavailable data
in electronic database
- 201 repeated isolate

SC

Study patients
367 controls included for analysis

AC
C

EP

TE
D

M
AN
U

Figure 1 Selection of study patients.

M
AN
U

SC

RI
PT

ACCEPTED MANUSCRIPT

AC
C

EP

TE
D

Figure 2 Discrimination of ESBL-EC infection based on ESBL infection risk scores

100
90
80
70
60
50
40
30
20
10
0

non-ESBL infection

low

moderate
Risk level

high

AC
C

EP

TE
D

M
AN
U

Figure 3 Distribution of ESBL infection risk level

RI
PT

ESBL infection

SC

Percentage in each level

ACCEPTED MANUSCRIPT

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