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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 4  |  Page : 257-261

Risk factor for urinary tract infections caused by Gram-negative Escherichia coli extended spectrum ß lactamase-producing bacteria


1 Department of Pharmacy, King Fahd Central Hospital, Jazan, Saudi Arabia
2 Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
3 Department of Pathology and Laboratory Medicine, King Saud University, King Saud University Medical City, Riyadh, Saudi Arabia
4 Division of Infectious Diseases, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Date of Submission03-Feb-2020
Date of Decision09-Mar-2020
Date of Acceptance10-Apr-2020
Date of Web Publication15-Jul-2020

Correspondence Address:
Abdullah Saleh Alsultan
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451
Saudi Arabia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JNSM.JNSM_11_20

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  Abstract 


Aim: The incidence of urinary tract infections (UTIs) due to extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli is increasing worldwide. Infections with ESBL-producing E. coli are associated with prolonged length of hospital stay, cost, and need for parenteral therapy. This study was aimed to describe the prevalence and assess the risk factors of UTIs due to ESBL-producing E. coli and to describe the antimicrobial susceptibility patterns against E. coli. Methods: A retrospective, cross-sectional study was conducted at King Saud University Medical City from May 1, 2015, to May 1, 2016, and included all adult cases of UTIs caused by E. coli.Results: E. coli urine isolates were obtained from 301 patients; 107 (35.5%) isolates had ESBL-producing E. coli, and 194 (64.5%) had non-ESBL E. coli. On multivariate analysis, urinary catheterization (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.17–1.55, P < 0.00), antibiotic use in the past 3 months, (OR 1.3, 95% CI 1.16–1.4, P < 0.00), and diabetes mellitus (OR 1.2, 95% CI 1.04–1.31, P < 0.00) were significantly associated with ESBL-producing E. coli. infection. As expected, these ESBL producing isolates demonstrated higher resistance compared to non-ESBL E. coli to trimethoprim/sulfamethoxazole (64.5% vs. 43.8%), ciprofloxacin (64.4% vs. 28.7%), and gentamycin (36.4% vs. 9.2%). Conclusion: About one-third of UTI patients with E. coli presented with ESBL-producing bacteria. Significant risk factors were urinary catheterizations, history of antibiotic use, and diabetes mellitus. However, the associated OR was low for all predictors indicating their limited value in identifying patients at risk of ESBL.

Keywords: Drug resistance, Escherichia coli, extended spectrum ß-lactamases, urinary tract infections


How to cite this article:
Majrashi AA, Alsultan AS, Balkhi B, Somily AM, Almajid FM. Risk factor for urinary tract infections caused by Gram-negative Escherichia coli extended spectrum ß lactamase-producing bacteria. J Nat Sci Med 2020;3:257-61

How to cite this URL:
Majrashi AA, Alsultan AS, Balkhi B, Somily AM, Almajid FM. Risk factor for urinary tract infections caused by Gram-negative Escherichia coli extended spectrum ß lactamase-producing bacteria. J Nat Sci Med [serial online] 2020 [cited 2020 Oct 24];3:257-61. Available from: https://www.jnsmonline.org/text.asp?2020/3/4/257/289805




  Introduction Top


Urinary tract infections (UTIs) are one of the common types of infections in the world.[1]Escherichia coli is the most common causative pathogen responsible for community and healthcare-associated UTIs.[1] Strains of gram-negative bacteria, which release enzymes called the extended-spectrum ß-lactamases (ESBL) were first recognized in Europe in 1980. These ESBL enzymes are mostly produced by E. coli and Klebsiella pneumoniae.[2] ESBL-producing bacteria are resistant to penicillins, monobactams, and third-generation cephalosporins, but usually remain susceptible to carbapenems.[3] Over the past two decades, we have seen an increase in the prevalence of UTIs caused by ESBL-producing Gram-negative organisms. This makes the treatment of UTIs more challenging. Cross-resistance with fluoroquinolone and aminoglycosides is common.[4],[5] Therefore, carbapenems are usually considered the treatment of choice for the infections caused by ESBL-producing bacteria.[3] Infections caused by ESBL-producing organisms are associated with increased cost, length of hospital stay, and need for outpatient parenteral therapy.[6]

There are a few studies that assessed the epidemiology of UTIs caused by E. coli ESBL in Saudi Arabia. However, these studies focused on the prevalence of ESBL-producing E. coli with no focus on risk factors. The two studies that have assessed the risk factors in the Saudi population reported the following risk factors: Renal disease and renal transplant, recurrent UTIs, diabetes, previous hospitalization, and antibiotic use.[7],[8]

A previous study describing the epidemiology of UTI at King Saud University Medical City demonstrated that ESBL prevalence was highest among patients with E. coli. Therefore, a further analysis focusing on ESBL caused by E. coli is warranted to explore this issue in more detail.[9] The primary objective of this study was to identify the risk factors associated with UTIs caused by ESBL-producing E. coli. A secondary objective was to describe the antimicrobial susceptibility patterns of ESBL and non-ESBL-producing E. coli.


  Methods Top


Study design

This is a retrospective, cross-sectional study conducted at King Saud University Medical City. Adult patients aged >18 years with a culture-confirmed UTI caused by E. coli, who required treatment from May 1, 2015, to May 1, 2016, were included in the study. The Infectious Diseases Society of America treatment guidelines were followed to identify patients diagnose with UTIs, discover its source (community vs. hospital), and determine its complexity.[10],[11]

Data collection

Data collected from patients' electronic medical records at King Saud University Medical City included: age, gender, patients' comorbidity, type of UTIs, antibiotic use in the past 3 months, the presence of an indwelling catheter, symptomatic or asymptomatic, and history of urological surgeries.

Laboratory detection of extended-spectrum ß-lactamases strains

All significant Enterobacteriaceae bacteria including K. pneumoniae, K. oxytoca, E. coli, and P. mirabilis isolates from urine samples were tested by the commercial automated identification and antimicrobial susceptibility system, MicroScan WalkAway-96 plus using MicroScan ESβL plus® Panels (Beckman Coulter Inc., Brea, CA, USA) according to the manufacturer's recommendation and our hospital protocol. The E-test method (AB Biodisk, Solna, Sweden) was performed to confirm the minimum inhibitory concentrations for third-generation cephalosporins. Results were interpreted according to the 2014 Clinical and Laboratory Standards Institute guidelines®. The American Type Culture Collection (ATCC) control strains Escherichia coli ATCC® 25922 Pseudomonas aeruginosa ATCC® 27853 (for carbapenems) Escherichia coli ATCC® 35218 for ß-lactam/ß-lactamase inhibitor combinations.[12]

Data analysis

For continuous covariates, we described the mean and standard deviations (SD). For categorical covariates, we used percentages. To compare between continuous variables, we used the independent t-test. For categorical variables, we used the Chi-square test. Logistic regression was used for the multivariable analysis to identify the independent risk factors of UTI. Any risk factor with value of P < 0.05 was considered for inclusion in the multivariable logistic regression. All statistical analyses were performed using the R statistical software. Value of P < 0.05 was considered statistically significant.

Ethical considerations

Ethical approval was obtained from the Institutional Review Board at King Saud University Medical City.


  Results Top


Epidemiology of urinary tract infections at King Saud University Medical City

During the study period, 301 patients were identified with culture-confirmed E. coli and required treatment. Among the 301 patients with positive E. coli isolates, 107 (35.5%) were infected with ESBL-producing E. coli and 194 (64.5%) with non-ESBL E. coli. [Table 1] shows the clinical characteristics of patients. The mean (±SD) age of patients with ESBL-producing and non-producing E. coli was 52.6 (±20.6) years and 46.3 (±19.7) years. In patients with community-acquired UTI, 28% were ESBL, whereas in patients with hospital-acquired UTI 55% were ESBL
Table 1: Clinical characteristics of patients

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Risk factor analysis

In the univariate analysis, significant covariates were diabetes mellitus, recurrent UTIs, urinary catheterizations, antibiotic use in the past 3 months, infections source, and male gender [Table 2]. On multivariate analysis, urinary catheterizations (OR 1.4, 95% confidence interval [CI] 1.17–1.55, P < 0.00), antibiotic use in the past 3 months, (OR 1.3, 95% CI 1.16–1.4, P < 0.00), and diabetes mellitus (OR 1.2, 95% CI 1.04–1.31, P < 0.00) were significantly associated with ESBL-producing E. coli [Table 3].
Table 2: Patients demographics and univariate analysis of risk factors and comorbidity

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Table 3: Multivariate analysis of risk factors associates with urinary tract infections

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Antimicrobial susceptibility

ESBL-producing E. coli demonstrated high resistance to trimethoprim/sulfamethoxazole (TMP/SMX) (64.5%), followed by fluoroquinolones (ciprofloxacin, 64.4% and levofloxacin, 61.7%), amoxicillin/clavulanic acid (46%), and gentamycin (36.4%). Non-ESBL E. coli showed a lesser degree of resistance for TMP/SMX (43.8%), fluoroquinolones (ciprofloxacin, 28.7% and levofloxacin, 23.7%), and gentamycin (9.2%). In this study, ESBL-producing E. coli of community-origin showed higher resistance compared to ESBL-producing E. coli of hospital origin TMP/SMX (68% vs. 60%), ciprofloxacin (71% vs. 56%), levofloxacin (63% vs. 60%), and gentamycin (40% vs. 30%). Antimicrobial susceptibility patterns for patients with ESBL-producing E. coli and non-ESBL-producing E. coli are shown in [Table 4].
Table 4: Antimicrobial susceptibly patterns

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  Discussion Top


We retrospectively described the prevalence of ESBL-producing E. coli isolated from the patient's urine samples and identified three significant risk factors (urinary catheterizations, history of antibiotics uses, and diabetes mellitus). The odds ratio (OR) for all three predictors was low, suggesting their limited role in identifying patients at risk of ESBL infection.

Several studies in Saudi Arabia reported center-specific prevalence of ESBL-producing E. coli from urinary isolates, ranging from 5.13% to 33.3%.[8],[13]E. coli-producing ESBL from urinary isolates at King Saud University Medical City has been slightly increasing in the past decade, from 29.0% to 33.3%.[8],[14] This could be explained by the increasing use of broad-spectrum antibiotics.[15] Our study reported a slight increase in the prevalence of ESBL-producing E. coli in King Saud University Medical City from 33.3% in 2013 to 35.5%. In addition, more than a quarter of urine isolates of community origin were ESBL. This increase should be taken into consideration since these patients may not respond to standard treatment of community-acquired UTI. In the Gulf region, one study examined the prevalence of UTIs caused by ESBL-producing E. coli in Kuwait and reported a prevalence rate of 16.4%.[16] Worldwide, the prevalence of ESBL-producing E. coli varies widely by country. The reported prevalence in the USA is 18.3%, Canada 13%, Brazil 55.2%, Mexico 21%, Bulgaria 40%, United Kingdom 10.3%, Thailand 39%, India 37.5%, Egypt 88.6%, and Sudan 59.6%.[17],[18],[19],[20]

In this study, urinary catheterizations, antibiotics use, and diabetes mellitus were found to be associated with ESBL-producing E. coli. This is consistent with prior studies that assessed risk factors for ESBL infections.[19],[21],[22] In prior studies, exposure to second -cephalosporin cefuroxime,[23] third-generation cephalosporin,[24] fluoroquinolones,[24],[25] penicillins, and aminopenicillins[19],[25] were associated with ESBL-producing E. coli.

ESBL-producing E. coli demonstrated high resistance to antimicrobial agents that are used as empirical therapy for UTIs such as TMP/SMX, ciprofloxacin, and amoxicillin/clavulanic acid. These results are consistent with the prior study by[8] at the same hospital. In this study, ESBL-producing E. coli isolated from community origin showed even higher rates of resistance compared to hospital isolates. This could be explained by the high antibiotic misuse in community practice.[15] From April 2018, the ministry of health in Saudi started enforcing the policy of not selling antibiotics from community pharmacies without a prescription. This is a step in the right direction, but more policies and guidelines are needed to decrease threats of antimicrobial resistance and improve patients care. Another concerning point from our study is that even non-ESBL–producing E. coli isolates still showed high resistance against some first-line options for the treatment of UTI such as TMP/SMX and ciprofloxacin.

Carbapenems are still considered the drug of choice for ESBL-producing E. coli[3] In this study, the susceptibility of E. coli was approximately 99.1% for ertapenem, imipenem, and meropenem. ESBL-producing E. coli showed low resistance to piperacillin/tazobactam 4.7%. Evidence supports the use of B-lactam/b-lactamase inhibitors such as piperacillin/tazobactam for the treatment of ESBL UTI, especially for noncomplicated cases.[26],[27] However, a recently published randomized control trial showed piperacillin-tazobactam was inferior to meropenem for the treatment of bloodstream infections caused by ESBL,[28] although for a different site, this study raises questions on whether B-lactam/b-lactamase inhibitors can be used for ESBL infections. Fosfomycin is an antibiotic has broad-spectrum activity against Gram-positive pathogen, including methicillin-resistant Staphylococcus aureus and Gram-negative, including multidrug resistance with ESBL production pathogens.[29] Although fosfomycin not tested in this study, fosfomycin remains active against ESBL production uropathogens with low resistance rate and may considered an alternative option for the treatment of UTI with ESBL producing E. coli.[5],[30]

There is a need to implement antimicrobial stewardship programs (APS) across the country. APS can have a positive impact in improving patients care, reduce hospital costs and decrease antimicrobial resistance.[31] A study in a tertiary care university hospital in Saudi Arabia found the implementation of APS was a safe and cost-effective strategy for controlling antibiotic prescribing and decrease antimicrobial resistance. APS reduced antibiotic consumptions by 67.2% and the monthly cost-saving were $326,020.[32]

Our study has limitations, including its retrospective design, small sample size, and being a single-center study. For antimicrobial use, we did not have the specific antibiotic class each patient use. Furthermore, we did not evaluate clinical outcomes or costs associated with ESBL infections in comparison to non ESBL infections. In addition, we did not perform genotyping for the ESBL isolates in our study larger multicenter studies are needed to evaluate the risk factors in our populations.


  Conclusion Top


The prevalence of ESBL-producing E. coli was relatively high in our center and has been steadily increasing. The risk factors identified, such as urinary catheterizations, history of antibiotic use, and diabetes mellitus, had a low OR indicating their limited value in identifying patients at risk of ESBL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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