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Erschienen in: BMC Infectious Diseases 1/2022

Open Access 01.12.2022 | Research

A clinical prediction tool for extended-spectrum β-lactamase-producing Enterobacteriaceae urinary tract infection

verfasst von: Hui Liu, Suishan Qiu, Minghao Chen, Jun Lyu, Guangchao Yu, Lianfang Xue

Erschienen in: BMC Infectious Diseases | Ausgabe 1/2022

Abstract

Background

Prevalence of extended-spectrum beta-lactamase-producing-Enterobacteriaceae (ESBL-E) has risen in patients with urinary tract infections. The objective of this study was to determine explore the risk factors of ESBL-E infection in hospitalized patients and establish a predictive model.

Methods

This retrospective study included all patients with an Enterobacteriaceae-positive urine sample at the first affiliated hospital of Jinan university from January 2018 to December 2019. Antimicrobial susceptibility patterns of ESBL-E were analyzed, and multivariate analysis of related factors was performed. From these, a nomogram was established to predict the possibility of ESBL-E infection. Simultaneously, susceptibility testing of a broad array of carbapenem antibiotics was performed on ESBL-E cultures to explore possible alternative treatment options.

Results

Of the total 874 patients with urinary tract infections (UTIs), 272 (31.1%) were ESBL-E positive. In the predictive analysis, five variables were identified as independent risk factors for ESBL-E infection: male gender (OR = 1.607, 95% CI 1.066–2.416), older age (OR = 4.100, 95% CI 1.678–12.343), a hospital stay in preceding 3 months (OR = 1.872, 95% CI 1.141–3.067), invasive urological procedure (OR = 1.810, 95% CI 1.197–2.729), and antibiotic use within the previous 3 months (OR = 1.833, 95% CI 1.055–3.188). In multivariate analysis, the data set was divided into a training set of 611 patients and a validation set of 263 patients The model developed to predict ESBL-E infection was effective, with the AuROC of 0.650 (95% CI 0.577–0.725). Among the antibiotics tested, several showed very high effectiveness against ESBL-E: amikacin (85.7%), carbapenems (83.8%), tigecycline (97.1%) and polymyxin (98.2%).

Conclusions

The nomogram is useful for estimating a UTI patient’s likelihood of infection with ESBL-E. It could improve clinical decision making and enable more efficient empirical treatment. Empirical treatment may be informed by the results of the antibiotic susceptibility testing.
Hinweise
Hui Liu and Suishan Qiu contributed equally to this work

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background

Extended-spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) are a diverse family of Gram-negative bacteria, mainly Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae), which express a clinically concerning drug resistance mechanism [1]. ESBL-E can hydrolyze and eliminate most broad-spectrum β-lactam antibiotics. Compared with non-ESBL-E infections, serious infections caused by ESBL-E have higher morbidity and mortality [2].
ESBL-E hydrolysis of carbapenem antibiotics is low, so carbapenem antibiotics are often used as the first choice in clinical treatment of ESBL-E infections. However, the abuse of carbapenems may result in the selection of carbapenem resistant Enterobacteriaceae, which will ultimately make it more difficult to treat this kind of bacteria [3, 4].
UTIs are the most common class of infectious disease, and antibiotics are their main means of treatment. The most common pathogen group in urine cultures is PE, which accounts for 30% to 40% of all urine culture bacteria [5]. In recent years, ESBL-E infection has been on the rise, and it is the main cause of hospital and community-acquired infections. In a study of antimicrobial resistance trends from 2010 to 2013, ESBL-E was frequently detected in China and Southeast Asia, and the ESBL production rate of E. coli and K. pneumoniae in some Asian countries was as high as 60% [6]. A study by Vachvanichsanong estimated that ESBL-E represented one-third of all E. coli and K. pneumoniae UTI episodes [7]. Data from the CHINET antimicrobial resistance monitoring project shows that the ESBL-producing isolates resistant to 3rd generation of cephalosporins increasing from 52.2 to 63.2% between 2005 and 2014 in China [8].
Several studies have suggested that infections caused by ESBL-E have an important clinical impact, and the growing prevalence of these microorganisms in hospitals had been well proven [2, 4]. Urinary tract infections (UTIs) are the main type of bacterial infection in hospitalized patients, and many of these exhibit resistances to the first-line antibiotics usually used to treat UTIs. Infections caused by ESBL-E frequency increased at a faster rate in health associated settings than in the community between 2014 and 2020 [9]. Patients who are identified to be at risk of ESBL-E infection can have their treatment empirically tailored to reduce treatment failure, complications, and antibiotic costs, and to avoid improper use of carbapenem drugs, reducing the risk of selecting drug-resistant microorganisms [10].
A key component of managing ESBL-E infection is to predict its incidence. A highly accurate predictive model can help identify high-risk patients and prevent or reduce the incidence of ESBL-E infection. However, neither test indicators nor imaging tests can yet predict ESBL-E infection. Therefore, this study aims to determine the prevalence and risk factors of ESBL-E infection in hospitalized patients with urinary tract infections and to establish a reliable predictive model.

Methods

Study population

This study was conducted at a university-affiliated tertiary hospital with 1900 beds. This study was conducted at the first affiliated hospital of Jinan university, a university-affiliated tertiary hospital in Guangzhou, China with 1900 beds. All cases from January 2018 to December 2019 in which all of a patient’s urine cultures tested positive for Enterobacteriaceae were reviewed. All non-repetitive mid-stream urine (MSU) samples obtained during the study period with a positive urine culture of either E. coli or K. pneumoniae were included in the analysis. In the annual microbiological epidemiology report of our hospital, 95% of the urine bacterial culture results were E coli and K. pneumoniae, and Proteus mirabilis and Salmonella accounted for the remaining 5%. However, no strains of ESBL positive were found in the strains of Proteus mirabilis and Salmonella, so these two types of bacteria were not included in this study. UTIs were defined in accordance with uniform diagnostic criteria of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [11]. Patients were excluded from the study if their medical records were missing data or if one or more of their samples were multi-microorganismal-defined as containing two or more pathogenic species in the same urine culture medium.

Data collection and definitions of variables

To identify predictors of urinary tract infections caused by ESBL-E, we referred to previously reported studies on risk factors related to multidrug resistance, including ESBL. Demographic and clinical data were obtained from medical records. The collected variables included age, gender, comorbid diseases, hospital admission history, undergoing an invasive urological procedure (such as intubation or catheterization), treatment history, and antibiotic use in the past 3 months. Comorbid diseases included chronic diabetes mellitus, chronic renal failure, immunodeficiency, neoplasia, recurrent UTIs, and severe underlying disease. Hospital admission history included such items as admission times, hospital stays in preceding 3 months, and admission history to the medical department, surgical department, or ICU.

Susceptibility testing

The drug susceptibility test used the paper diffusion method in accordance with the Clinical Laboratory Standards Institute (CLSI). The minimum inhibitory concentration (MIC) was passed through the Vitek 2 automated microbial identification system (Vitek AMS; bioMerieux Vitek Systems Inc., Hazelwood, Missouri). All results met the CLSI Enterobacteriaceae standards. Six types of antibacterial agents were tested: β-lactam/β-lactam Enzyme inhibitor combination (cefoperazone-sulbactam, piperacillin-tazobactam), cephalexin (ceftazolin, cefotaxime, ceftazidime, ceftriaxone, cefepime), carbapenem (imipenem, meropenem), aminoglycoside (amikacin), folate pathway inhibitor (trimethoprim-sulfamethoxazole), and fluoroquinolone (Levofloxacin) (Sigma-Aldrich, St. Louis, Missouri). Quality control was performed on E. coli (ATCC 25922) and K. pneumoniae (ATCC 700603) [12].

Statistical analysis

As age and admission times are continuous variables with non-normal distribution, both were grouped into categories (0–18 years, 18–60 years, 60+ years); thus, all data existed in the form of categorical variables. We first numbered 874 patients, randomly sampled the numbers with the “sample” command in R software, and used the “set. Seed” and ind <-sample (n, 0.7 * n) commands at the same time. The randomly sampled patients were divided into a training set and a validation set. 611 patients (70% of the study) were randomly selected as the training set, and 263 patients (the other 30%) were selected as the validation set. Internal verification was carried out using a resampling-based method. Pearson's chi-square test or Fisher's exact test was used to compare differences between data sets, as appropriate, and for univariate analysis in the training set. All variables with a P value less than 0.1 in the univariate analysis were input into the multivariate analysis to further select the variables in the predictive model.
A predictive model was established by applying multivariate logistic regression with variables selected from multivariate analysis. The risk predictive model of ESBL-E infection was presented using a nomogram. The predictive model was evaluated on three criteria: discriminatory capacity, calibration ability, and clinical effectiveness. The AuROC was used to evaluate discriminative ability. The calibration curve and Hosmer–Lemeshow test were used to evaluate its calibration ability. Decision curve analysis (DCA) was used to evaluate clinical efficacy. All tests were two-tailed, and a P value of less than 0.05 was considered statistically significant. All statistical analyses were performed using R software (version 3.6.3, Vienna, Austria).

Results

Demographics and clinical characteristics

Figure 1 shows the overall experimental flow. The organisms of interest, E. coli and K. pneumoniae, were identified in urine cultures from 885 unique patients during the study period. Of these, 11 were removed from the dataset: 9 cases were missing data, and 2 cases were identified to contain 2 pathogenic species. Table 1 shows a comparison of the demographic and clinical factors between the ESBL-E and non-ESBL-E patients. The median (IQR) ages at presentation were 65.5 (52–76) years for the ESBL-E group and 61 (49–74) years for the non-ESBL-E group (P < 0.001). The proportions of ESBL-E infections among males and females were 33.5% and 66.5%, respectively (P = 0.05). The two groups were compared across numerous factors: several comorbid diseases, hospital admission history, invasive urological procedure treatment history, and antibiotic use in the past 3 months. Those which showed significant differences (P < 0.05) were: diabetes mellitus, severe underlying disease, a hospital stay in the preceding 3 months, prior admission to the medical department, prior admission to the surgical department, prior admission to the ICU, undergoing an invasive urological procedure, and antibiotic use in the past 3 months. Among microorganisms, E. coli (739 cases, 84.6%) was the most commonly isolated species, with K. pneumoniae (135 cases, 15.4%) comprising the remainder.
Table 1
Demographic data, clinical characteristics
Variables
Overall (n = 874)
Non-ESBL-E (n = 602)
ESBL-E
(n = 272)
P value
Gender, n (%)
   
0.050
Male
236 (27.0)
145 (24.1)
91 (33.5)
 
Female
638 (73.0)
457 (75.9)
181 (66.5)
 
Age (years), [median (IQR)]
62.0 (50–75)
61 (49–74)
65.5(52–76)
 < 0.001
Comorbidity diseases
 Diabetes mellitus, n (%)
   
0.038
  Yes
287 (32.8)
211 (35.0)
76 (27.9)
 
  No
587 (67.2)
391 (65.0)
196 (72.1)
 
 Chronic renal failure, n (%)
  
0.208
  Yes
123 (14.1)
91 (15.1)
32 (11.8)
 
  No
751 (85.9)
511 (84.9)
240 (88.2)
 
 Immunodeficiency, n (%)
  
0.056
  Yes
51 (5.8)
29 (4.8)
22 (8.1)
 
  No
823 (94.2)
573 (95.2)
250 (91.9)
 
 Neoplasia, n (%)
   
0.072
  Yes
103 (11.8)
63 (10.5)
40 (14.7)
 
  No
771 (88.2)
539 (89.5)
232 (85.3)
 
 Recurrent Urinary tract infections, n (%)
  
 < 0.001
  Yes
134 (15.3)
66 (11.0)
68 (25.0)
 
  No
740 (84.7)
536 (89.0)
204 (75.0)
 
 Severe underlying disease, n (%)
  
0.009
  Yes
66 (7.6)
36 (6.0)
30 (11.0)
 
  No
808 (92.4)
566 (94.0)
242 (89.0)
 
 Hospital stays in preceding 3 months, n (%)
  
 < 0.001
  Yes
309 (35.4)
168 (27.9)
141 (51.8)
 
  No
565 (64.6)
434 (72.1)
131 (48.2)
 
Previous hospitalization department
 Medical department, n (%)
  
0.005
  Yes
265 (30.3)
165 (27.4)
100 (36.8)
 
  No
609 (69.7)
437 (72.6)
172 (63.2)
 
 Surgical department, n (%)
   
 < 0.001
  Yes
174 (19.9)
99 (16.4)
75 (27.6)
 
  No
700 (80.1)
503 (83.6)
197 (72.4)
 
 Intensive Care Unit (ICU), n (%)
  
0.047
  Yes
10 (1.1)
4 (0.7)
6 (2.2)
 
  No
864 (98.9)
598 (99.3)
266 (97.8)
 
 Invasive urological procedure, n (%)
  
 < 0.001
  Yes
269 (30.8)
150 (24.9)
119 (43.8)
 
 No
605 (69.2)
452 (75.1)
153 (56.3)
 
 Antibiotic use in the past 3 months, n (%)
  
 < 0.001
  Yes
190 (21.7)
91 (15.1)
99 (36.4)
 
  No
684 (78.3)
511 (84.9)
173 (63.6)
 
 Microorganism, n (%)
  Escherichia coli
739 (84.6)
540 (89.7)
199 (73.2)
 < 0.001
  Klebsiella sp.
135 (15.4)
62 (10.3)
73 (26.8)
 < 0.001
 Mortality, n (%)
  Secondary to infection
6 (0.7)
4 (0.7)
2 (0.7)
0.604
  Other cause
7 (0.8)
3 (0.5)
4 (1.5)
0.140
Following random sampling, 611 patients, including 191 (31.3%) ESBL-E patients, were included in the training set. The remaining 263 patients, with 82 (31.2%) ESBL-E patients, were assigned to the validation set. No significant difference in the variables was observed between the training validation sets (all P > 0.05), as shown in Table 2.
Table 2
Clinical features and risk factor exposition in the study population
Variables
Overall (n = 874)
Training set (n = 611)
Validation set (n = 263)
P value
Status, n (%)
   
0.981
 ESBL−
602 (68.9)
420 (68.7)
181 (68.8)
 
 ESBL+ 
272 (31.1)
191 (31.3)
82 (31.2)
 
Gender, n (%)
   
0.111
 Male
236 (27.0)
176 (28.8)
62 (23.6)
 
 Female
638 (73.0)
435 (71.2)
201 (76.4)
 
Age, n (%)
   
0.543
 0 to 18 years
70 (8.0)
49 (8.0)
21 (8.0)
 
 18 to 60 years
309 (35.4)
209 (34.2)
100 (38.0)
 
 Over 60 years
495 (56.6)
353 (57.8)
142 (54.0)
 
Comorbidity diseases
 Diabetes mellitus, n (%)
   
0.920
  Yes
287 (32.8)
200 (32.7)
87 (33.1)
 
  No
587 (67.2)
411 (67.3)
176 (66.9)
 
 Chronic renal failure, n (%)
   
0.998
  Yes
123 (14.1)
86 (14.1)
37 (14.1)
 
  No
751 (85.9)
525 (85.9)
226 (85.9)
 
 Immunodeficiency, n (%)
   
0.913
  Yes
51 (5.8)
36 (5.9)
15 (5.7)
 
  No
823 (94.2)
575 (94.1)
248 (94.3)
 
 Neoplasia, n(%)
   
0.170
  Yes
103 (11.8)
78 (12.8)
25 (9.5)
 
  No
771 (88.2)
533 (87.2)
238 (90.5)
 
Recurrent Urinary tract infections, n (%)
  
0.496
 Yes
134 (15.3)
97 (15.9)
37 (14.1)
 
 No
740 (84.7)
514 (84.1)
226 (85.9)
 
 Severe underlying disease, n (%)
   
0.056
  Yes
66 (7.6)
53 (8.7)
13 (4.9)
 
  No
808 (92.4)
558 (91.3)
250 (95.1)
 
Hospital admission history
 Admission times, n (%)
   
0.555
  1 to 2 times
645 (73.8)
455 (74.5)
190 (72.2)
 
  3 to 6 times
159 (18.2)
111 (18.2)
48 (18.3)
 
  More than 6 times
70 (8.0)
45 (7.4)
25 (9.5)
 
 Hospital stay in preceding 3 months, n (%)
  
0.645
  Yes
309 (35.4)
219 (35.8)
90 (34.2)
 
  No
565 (64.6)
392 (64.2)
173 (65.8)
 
Previous hospitalization department
 Medical department, n (%)
   
0.905
  Yes
265 (30.3)
186 (30.4)
79 (30.0)
 
  No
609 (69.7)
425 (69.6)
184 (70.0)
 
 Surgical department, n (%)
  
0.111
  Yes
174 (19.9)
113 (18.5)
61 (23.2)
 
  No
700 (80.1)
498 (81.5)
202 (76.8)
 
 Intensive Care Unit (ICU), n (%)
   
0.724
  Yes
10 (1.1)
8 (1.3)
2 (0.8)
 
  No
864 (98.9)
603 (98.7)
261 (99.2)
 
Treatment history
 Invasive urological procedure, n (%)
  
0.880
  Yes
269 (30.8)
189 (30.9)
80 (30.4)
 
  No
605 (69.2)
422 (69.1)
183 (69.6)
 
 Antibiotic use in the past 3 months, n (%)
  
0.570
  Yes
190 (21.7)
136 (22.3)
54 (20.5)
 
  No
684 (78.3)
475 (77.7)
209 (79.5)
 

Independent risk factors in the training set

The risk factor analysis was based on the 874 patients in the training set. Univariate and multivariate analysis for ESBL-E infection is shown in Table 3. Eleven variables were identified by univariate analysis (P < 0.1): gender, age, immunodeficiency, urinary tract infections, severe underlying disease, hospital stay in preceding 3 months, prior admission to medical department, prior admission to surgical department, prior admission to ICU, prior invasive urological procedure, and antibiotic use in the past 3 months.
Table 3
Univariate and Multivariate analysis in the training set
Variables
Univariate
Multivariate
OR
95% CI
P value
OR
95% CI
P value
Gender
 Male
1.654
1.143–2.388
0.0073
1.607
1.066–2.416
0.023
 Female
Reference
  
Reference
  
Age
 0 to 18 years
Reference
  
Reference
  
 18 to 60 years
3.712
1.529–11.108
0.008
2.825
1.119–8.679
0.043
 Over 60 years
4.765
2.015–14.035
0.001
4.100
1.678–12.343
0.005
Diabetes mellitus
 Yes
0.884
0.610–1.274
0.513
   
 No
Reference
     
Chronic renal failure
 Yes
0.886
0.529–1.446
0.637
   
 No
Reference
     
Immunodeficiency
 Yes
1.829
0.914–3.606
0.082
1.671
0.770–3.579
0.187
 No
Reference
  
Reference
  
Neoplasia
 Yes
1.444
0.875–2.351
0.143
   
 No
Reference
     
Recurrent urinary tract infections
 Yes
2.181
1.398–3.396
 < 0.001
1.145
0.645–2.011
0.639
 No
Reference
  
Reference
  
Severe underlying disease
 Yes
2.294
1.295–4.058
0.004
1.536
0.805–2.907
0.188
 No
Reference
  
Reference
  
Admission times
 1 to 2 times
Reference
     
 3 to 6 times
1.047
0.664–1.627
0.841
   
 More than 6 times
1.380
0.719–2.580
0.320
   
Hospital stay in preceding 3 months
 Yes
3.067
2.152–4.389
 < 0.001
1.872
1.141–3.067
0.013
 No
Reference
  
Reference
  
Medical department
 Yes
1.516
1.052–2.179
0.025
0.799
0.498–1.266
0.344
 No
Reference
  
Reference
  
Surgical department
 Yes
1.751
1.145–2.663
0.009
0.943
0.572–1.533
0.816
 No
Reference
  
Reference
  
Intensive Care Unit (ICU)
 Yes
3.737
0.907–18.370
0.073
1.693
0.346–9.816
0.524
 No
Reference
  
Reference
  
Invasive urological procedure
 Yes
2.792
1.945–4.017
 < 0.001
1.810
1.197–2.729
0.005
 No
Reference
  
Reference
  
Antibiotic use in the past 3 months
 Yes
3.231
2.179–4.807
 < 0.001
1.833
1.055- 3.188
0.031
 No
Reference
  
Reference
  
Multivariate analysis was performed with the eleven variables identified by univariate analysis. Five variables were proved to be independent predictors for ESBL-E infection: male gender (OR = 1.607, 95% CI 1.066–2.416), older age (OR = 4.100, 95% CI 1.678–12.343), a hospital stay in preceding 3 months (OR = 1.872, 95% CI 1.141–3.067), invasive urological procedure (OR = 1.810, 95% CI 1.197–2.729), and antibiotic use within the previous 3 months (OR = 1.833, 95% CI 1.055–3.188).

Predictive model construction and validation

An ESBL-E infection risk estimation nomogram model was developed by logistic regression using the five independent predictors (Fig. 2). When present, each of the predictors contributes between 30 and 100 points to a final point total. This point total is then used to estimate the probability that the patient should can diagnosed as ESBL-E positive. To calculate the probability of a patient having ESBL-E infection, identify patient values on each axis, then for each draw a vertical line upwards to the “Points” axis. This determines how many points each variable generates. Add the points for all variables and locate this sum on the “Total points” line. Then draw a vertical line downwards from this point and identify the recurrence risk probability of ESBL-E infection. Hospital stay = Hospital stay in preceding 3 months; IOP = invasive urological procedure; Antibiotic use = Antibiotic use in the past 3 months.
The AUC was used to evaluate the discriminatory capacity of the predictive model, and the nomogram demonstrated good accuracy in estimating the risk of ESBL-E infection. The AUC of ROC was 0.714 (95% CI 0.671–0.757) in the training set (Fig. 3A). In validation set, the AUC of ROC was 0.650 (95% CI 0.577–0.725) (Fig. 3B).
A calibration plot and Hosmer–Lemeshow test were used to the calibrate the predictive model (Fig. 4). The calibration curves show the predictive model and the validation set produce very good fits of the data. The Hosmer–Lemeshow test indicates that the predicted probability is highly consistent with the actual probability (training set, P = 0.999; validation set, P = 0.732). Decision curve analysis, shown in Fig. 5, was used to demonstrate the net benefits of this predictive model. Its strong predictive capacity allows for accurate diagnosis, which should result in better patient treatment than either non-diagnosis or full diagnosis.

Antibiotic susceptibility testing

Table 4 indicates the overall antimicrobial susceptibility of PE to the antibiotics tested. The highest sensitivity was observed with amikacin (94.7%), carbapenem (95.0%), polymyxin (99.2%), tigecycline (98.9%), and latamoxef (91.2%). Except for latamoxef and cefdinir, there are statistically significant (P < 0.05) differences in the susceptibility of all antibacterial drugs between the two groups.
Table 4
Antibiogram result of PE
Antibiotics
Antibiogram result
Total
SEN
P value
Non-ESBL-E
ESBL-E
S
I
R
SEN
S
I
R
SEN
Ciprofloxacin
304
24
265
51.3
39
5
220
14.8
857
40.0
 < 0.001
Levofloxacin
246
66
246
44.1
35
18
219
12.9
874
32.2
 < 0.001
P/T
580
14
8
96.3
167
35
69
61.6
873
85.6
 < 0.001
Ceftazidime
540
43
16
90.2
26
49
196
9.6
870
65.1
 < 0.001
C/S
590
7
3
98.3
166
31
75
61.0
872
86.7
 < 0.001
Cefepime
533
23
45
88.7
18
46
207
6.6
872
63.2
 < 0.001
Aztreonam
561
1
30
94.8
18
2
242
6.9
854
67.8
 < 0.001
Amikacin
595
4
3
98.8
233
4
35
85.7
874
94.7
 < 0.001
Tobramycin
438
115
39
74.0
127
53
81
48.7
853
66.2
 < 0.001
Carbapenem
602
0
0
100.0
228
0
44
83.8
874
95.0
 < 0.001
TMP-SMX
312
1
288
51.9
82
0
188
30.4
871
45.2
 < 0.001
Polymyxin
600
0
2
99.7
267
0
5
98.2
874
99.2
0.033
Doxycycline
271
123
204
45.3
73
43
155
26.9
869
39.6
 < 0.001
Minocycline
371
80
139
62.9
96
39
126
36.8
851
54.9
 < 0.001
Tigecycline
590
0
2
99.7
238
0
7
97.1
837
98.9
0.004
Cefixime
45
0
134
25.1
1
0
235
0.4
415
11.1
 < 0.001
Latamoxef
53
0
2
96.4
50
0
8
86.2
113
91.2
0.095
Cefdinir
1
0
20
4.8
1
0
93
1.1
115
1.7
0.333
Ceftriaxone
388
0
3
99.2
2
0
45
4.3
438
89.0
 < 0.001
Cefmetazole
92
0
0
100.0
4
0
14
22.2
110
87.3
 < 0.001
Ceftizoxime
39
0
0
100.0
0
0
10
0.0
49
79.6
 < 0.001
S, Sensitive; I, Intermediate; R, Resistant; SEN, Sensitivity, %; P/T, piperacillin/tazobactam; C/S, cefoperazone/sulbactam; TMP-SMX, trimethoprim–sulfamethoxazole

Discussion

In this study, we propose a valuable clinical tool to predict the possibility of ESBL producing organisms as the etiology of urinary tract infection in hospitalized patients. Our prediction tool consists of five variables, including three clinical categories: gender, age, hospital stay in the preceding 3 months, invasive urological procedures, and antibiotic use in the past 3 months. The scoring system is feasible in clinical practice because it contains patient factors that can be easily determined from medical records and can be implemented with minimal health system cost.
First, we found that older patients were significantly more likely to get ESBL-E infections. Older age more likely to get ESBL-E infections, which is in agreement with prior studies [13, 14]. Second, in univariate and multivariate regression analysis, gender specifically, being male is an independent risk factor. Many previous studies similarly consider being male a predictor of infection [10, 15]. Third, we showed that prior hospital stays were a predictor for ESBL-E infection. This comports well with previous work which shows that hospital stays increase the risk of carrying ESBL-E [16]. The epidemiology of these ESBL-producing bacteria is becoming more and more complicated [17]. Fourth, we included invasive urological procedures, such as intubation and catheterization, as an ESBL-E UTI predictor, in agreement with previously published literature [18]. Invasive procedures can damage the skin and mucous membranes, thereby increasing the chance of contact with ESBL-producing bacterial strains [19]. Lastly, in this study, we found an association between the use of antibiotics in the past 3 months and the occurrence of ESBL-E in UTI. The abuse of antibiotics in recent years has led to an increase in antibiotic resistance. ESBL-E colonization is a known risk factor for subsequent infection or bacteremia [20, 21]. Additionally, the improper use of antibacterial drugs has been shown to play a key role in the emergence of multi-drug resistant organisms. The selection of resistant forms may occur during or after antimicrobial treatment.
Further, comorbidities such as diabetes, chronic renal insufficiency, serious underlying diseases, and tumors were not considered predictors of UTIs caused by ESBL-E [22], and they were found to not be significant contributors in this study either.
Nomogram is based on multi-factor regression analysis, integrating multiple predictive indicators, and then using scaled line segments, drawn on the same plane according to a certain ratio, so as to express the relationship between the various variables in the prediction model mutual relations. The nomogram transforms the complex regression equation into a visualized graph, making the results of the prediction model more readable and facilitating the evaluation of the patient [23].
The production and evaluation of nomogram is in accordance with conventional methods. The ROC curves, Decision curve analysis and Calibration plots in the article are all evaluations of nomogram, indicating that our nomogram is reasonable. E.g., Assuming a patient of 65 age, male, who has no history of hospitalization, has not undergone surgery but has used antibiotics within three months. We calculate the total points are 160, then the probability of an ESBL-E infection is 38%. Our clinical prediction tool provides doctors with an easy-to-use mechanism to improve the method of determining which patients with urinary tract infection may need broad-spectrum antibiotic coverage. The purpose of wider spectrum coverage is to ensure that individuals are initially treated with appropriate antibiotics. The tool showed excellent discrimination in the derivation queue with AUC of 0.714, but only moderate discrimination in the verification queue with AUC of 0.650. Because urine samples are highly contaminated clinical biological samples, considering the high risk of urine contamination, the AUC of our prediction model is acceptable. Although our nomogram is not perfect and could not be 100% predicted, when patients find urinary tract infection, it has certain guiding significance for doctors' initial medication decision, and more reasonable antibiotics can be selected as soon as possible.
In addition to building a predictive model, numerous carbapenem antibiotics were tested against ESBL-E cultures to determine whether these resistant bacteria could be combatted by less-common treatments. A previous study found that there was a correlation between CTX-M-producing bacteria, one of the three most common ESBLs genes in E. coli and K. pneumoniae, and fluoroquinolones resistance [24]. They showed that ESBL-E had an 87.1% resistance rate to levofloxacin. It has been demonstrated that antibiotics (prophylactic or therapeutic) can induce antibiotic resistance genes that respond to ESBL-E infection [25]. Nonstandard antibiotic treatments, such as those explored here, are therefore necessary.
We showed that carbapenems and aminoglycosides, such as amikacin, seem to be good choices for the treatment of serious infectious diseases of ESBL-E, though they may introduce other complicating factors such as the need to closely monitor renal response. Previous studies have shown that the proportion of carbapenem-resistant producing-Enterobacteriaceae in UTIs is less than 3% [2628]. However, in this study, we found that carbapenem-resistant producing-Enterobacteriaceae could be as high as 5%, especially in the ESLB-E group, the resistance rate of carbapenems was 16.2%.
Tigecycline and polymyxin were also demonstrated to be highly effective against ESBL-E. Previous work has found that tigecycline has clinical effectiveness in the treatment of UTIs; however, its use is still controversial due to a lack of data and randomized controlled trials [29]. The authors recommended using tigecycline only in the absence of other potential treatments; if aminoglycosides or β-lactams can be used to treat UTI, tigecycline should be avoided. Similarly, while polymyxin is shown to be an effective treatment for UTIs, its partial conversion to colistin in the urine may induce nephrotoxicity, so it should be used with caution.
The effectiveness of piperacillin/tazobactam and cefoperazone/sulbactam against ESBL-E were about 60%. ESBLs are generally inhibited by tazobactam [18], which could be a suitable option for initial empirical medication of ESBL-E high-risk groups. Latamoxef showed high effectiveness against ESBL-E, but due to the small number of subjects using the drug, further verification is needed.
This study has several limitations and ways it could be improved in the future. First, it is a retrospective case–control study with election bias. Second, some data may be missing from the medical records. Third, this study was conducted in a large hospital in China, and only inpatients were recruited; therefore, patients may not be representative of the greater Chinese or world populations. Finally, the overall sample size was too small to include more research factors, but the age span of the population included in this study was large. In the next step of the research, we will increase the sample size, more stringent review of electronic medical records, sub-group analysis for different age groups, and external verification to optimize the model to improve prediction accuracy. Since the proportion of ESBL + resistant strains in our hospital have reached more than 30%, it is very valuable to find a clinical prediction model that could improve the drug resistance of urinary tract infections. Our prediction model is more suitable for hospitals with high ESBL + resistance rates as a reference.

Conclusion

The prevalence of ESBL-E in patients with urinary tract infections in the Chinese hospital system continues to grow, especially among men and the elderly. Hospitalization in the first 3 months, invasive urological procedures, and the use of antibiotics in the past 3 months further increase the risk of infection. The nomogram developed in this study can be used to identify high-risk patients. These patients may benefit from empirical antibiotic prescriptions, such as those explored in this study. Doing so may reduce the failure rate of treatment as promote responsible use of antibiotics which might otherwise contribute to the growing trend of antibiotic resistance.

Acknowledgements

Not applicable.

Declarations

This study was approved by the Ethics Committee of the First Affiliated Hospital of Jinan University. This study was carried out in compliance with the Declaration of Helsinki guidelines. Clinical Laboratory concluded that no informed consent was required because the data are anonymized appropriately.
Not applicable.

Competing interests

The authors declare that they have no competing interests.
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Metadaten
Titel
A clinical prediction tool for extended-spectrum β-lactamase-producing Enterobacteriaceae urinary tract infection
verfasst von
Hui Liu
Suishan Qiu
Minghao Chen
Jun Lyu
Guangchao Yu
Lianfang Xue
Publikationsdatum
01.12.2022
Verlag
BioMed Central
Erschienen in
BMC Infectious Diseases / Ausgabe 1/2022
Elektronische ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07040-y

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