Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: A matched cohort study

doi:10.1016/j.jinf.2015.08.012

Journal of Infection

Volume 71, Issue 6, December 2015, Pages 667-674

https://doi.org/10.1016/j.jinf.2015.08.012 Get rights and content

Highlights

•
We analyze the clinical and economic impact of UTI caused by ESBL-producing Escherichia coli. These infections have worse clinical outcomes than those caused by non-ESBL producers.
•
UTI due to ESBL-producing E. coli leads to increased consumption of health care resources.
•
UTI due to ESBL-producint E. coli increase antibiotic costs.

Summary

Objective

To analyze the clinical and economic impact of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli requiring hospitalization.

Methods

Matched cohort study including adults with UTI caused by ESBL-producing E. coli admitted to a tertiary care hospital in Barcelona, Spain, between August 2010 and July 2013. Demographic, clinical and economic data were analyzed.

Results

One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 due to non-ESBL-producing E. coli. Bivariate analysis showed that prior antimicrobial treatment (p = 0.007) and ESBL production (p < 0.001) were related to clinical failure during the first 7 days. Multivariate analysis selected ESBL as the sole risk factor for clinical failure (p = 0.002). Regarding the economic impact of infections caused by ESBL-producing E. coli, an ESBL-producing infection cost more than a non-ESBL-producing E. coli infection (mean €4980 vs. €2612). Looking at hospital expenses separately, the total pharmacy costs and antibiotic costs of ESBL infections were considerably higher than for non-ESBL infections (p < 0.001), as was the need for outpatient parenteral antibiotic therapy (OPAT) and its related costs. Multivariate analysis performed for the higher costs of UTI episodes found statistically significant differences for males (p = 0.004), chronic renal failure (p = 0.025), ESBL production (p = 0.008) and OPAT (p = 0.009).

Conclusion

UTIs caused by EBSL-producing E. coli requiring hospital admission are associated with worse clinical and economic outcomes.

Introduction

Extended-spectrum beta-lactamases (ESBLs) are enzymes produced by gram-negative bacilli capable of hydrolyzing broad-spectrum cephalosporins and monobactams as well as conferring high rates of resistance to other families of antibiotics.1, 2, 3 This peculiarity reduces both empirical and directed treatment options and is related to a worse prognosis.

ESBLs have been increasingly reported in Europe since they were first described in 1983. In the 1990s, they were described in Klebsiella pneumoniae as the cause of nosocomial outbreaks and are now often found in Escherichia coli, which cause community-acquired infections.4, 5, 6 The European Center for Disease Control (ECDC) registered an increase in ESBL-producing E. coli, from 1.1% in 2004 to 10.4% in 2013.⁷ In 2006, the Spanish Hospital Infection Study Group (GEIH) developed the second national survey of ESBL-producing E. coli and K. pneumonia in order to study the epidemiology and evolution of this problem in Spain. This study showed eight- and two fold increases in the percentage of ESBL-producing E. coli and K. pneumoniae isolates respectively since 2000, the vast majority of urinary origin. Interestingly, a high proportion of the isolated ESBL E. coli strains came from outpatients, approximately 32% of which could be considered community-acquired infections.⁸

Antimicrobial resistance hinders the treatment of UTI and increases the use of health care resources.9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 Our aim was to analyze the clinical and economic impact of UTIs caused by ESBL-producing versus non-ESBL-producing E. coli.

Section snippets

Methods

We conducted a matched cohort study from August 2010 to July 2013 in a university-affiliated 420-bed tertiary care hospital in Barcelona (Spain) serving a population of 300,000 people.

The study was approved by the Clinical Research Ethical Committee of the Parc de Salut Mar (CEIC – Parc de Salut Mar).

The case-cohort included adults (over 18 years old) admitted to the Hospital del Mar during the study period who had symptomatic UTI caused by ESBL-producing E. coli. The control cohort included

Data collection and variables analyzed

Data were retrospectively collected from electronic charts. The following variables were recorded: demographic and epidemiological factors (age, gender, underlying diseases, use of immunosuppressive therapy, prior treatment with antibiotics), clinical and microbiological data (fever at admission, bacteremia, severe sepsis or septic shock, ICU admission, adequacy of empirical antimicrobial treatment, time to adequate treatment, clinical response within 7 days, need for and number of successive

Definitions

Symptomatic UTI was established when the patient presented at least one of the following symptoms: increase of urinary frequency, urgency, dysuria or suprapubic tenderness associated with a positive urine culture (more than 10⁵ CFU of uropathogen per mL urine).

Four UTI syndromes were considered:

1.
Cystitis: the presence of dysuria and increased urinary frequency or urgency, with or without hematuria, in patients without fever (axillary temperature <37.5 °C).
2.
Pyelonephritis: presence of fever

Statistical analysis

Quantitative variables were analyzed using the Student's t-test and qualitative variables using the Chi-square test or Fisher's exact test, as appropriate. A multivariate logistic regression analysis was used to determine the independent variables related to the clinical and economic impact of ESBL-producing E. coli UTI. For the statistical analysis, a p value of <0.05 was considered significant. All data were analyzed using the SPSS 15.0 statistical package.

Results

One hundred and twenty episodes of UTI were studied: 60 due to ESBL-producing E. coli and 60 to non-ESBL-producing E. coli. Patient characteristics are described in Table 1. Among ESBL-producing E. coli infections, inadequate empirical treatment, a worse clinical response, increased LOS and greater need for OPAT were more frequently observed than among non-ESBL-producing infections. ESBL production was the only variable significantly related to clinical failure, while pyelonephritis was

Discussion

Infections caused by ESBL-producing Enterobacteriaceae are associated with inadequate empirically prescribed antibiotic treatment, poor clinical outcome and increased use of health care resources.11, 13, 14, 15, 16, 17 However, the information about the impact of UTI caused by ESBL-producing microorganisms comes principally from studies conducted with bacteremia.11, 14, 15, 16, 17, 19, 20 Our study was based on patients who all had a diagnosis of UTI and required hospitalization. The study

Conflict of interest

None.

Acknowledgments

We would like to thank Sergi Mojal for his support in the data analysis of this study. He is an experienced statistician currently responsible for methodological consultation in biomedical research at the IMIM, Hospital del Mar. He also carried out the statistical analysis for standardized monitoring of hospital antimicrobial consumption of the Surveillance of Health Care-Associated Infections in Catalonia (Spain) (VINCat program).

References (30)

D.J. Hoban et al.
Antimicrobial susceptibility of global inpatient urinary tract isolates of Escherichia coli: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program: 2009–2010
Diagn Microbiol Infect Dis
(2011)
R. Cantón et al.
Prevalence and spread of extended-spectrum beta-lactamase-producing Enterobacteriaceae in Europe
Clin Microbiol Infect
(2008)
Miguel Ángel Díaz et al.
Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Spanish hospitals: 2nd multicenter study (GEIH-BLEE project, 2006)
Enferm Infecc Microbiol Clin
(2009)
A.R. Marra et al.
Health and economic outcomes of the detection of Klebsiella pneumoniae-produced extended-spectrum beta-lactamase (ESBL) in a hospital with high prevalence of this infection
Int J Infect Dis
(2006)
M. Melzer et al.
Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli
J Infect
(2007)
M.E. Charlson et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987)
J. Rodríguez-Baño et al.
Programas de optimización de uso de antimicrobianos (PROA) en hospitales españoles: documento de consenso GEIH-SEIMC, SEFH y SEMPSPH
Enferm Infecc Microbiol Clin
(2012)
G.V. Bochicchio et al.
In vitro susceptibilities of Escherichia coli isolated from patients with intra-abdominal infections worldwide in 2002–2004: results from SMART (Study for Monitoring Antimicrobial Resistance Trends)
SurgInfect (Larchmt)
(2006)
A. Andreau et al.
Etiology of community-acquired lower urinary infections and antimicrobial resistance of Escherichia coli: a national surveillance study
Med Clin (Barc)
(2008)
T.M. Coque et al.
Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe
Eurosurveillance
(20 November 2008)

Antonio Oliver and Rafael Cantón. Enterobacterias productoras de beta-lactamasas plasmídicas de espectro extendido....

EARS-Net Report, Quarter 1 2014. June...

M.H. Kollef

Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients

Clin Infect Dis

(2000)

E. Lautenbach et al.

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes

Clin Infect Dis

(2001)

Mitchell J. Schwaber et al.

Clinical and economic impact of bacteremia with extended-spectrum-b-lactamase-producing Enterobacteriaceae

Antimicrob Agents Chemother

(Apr. 2006)

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View full text

Clinical and economic impact of urinary tract infections caused by ESBL-producing Escherichia coli requiring hospitalization: A matched cohort study

Highlights

Summary

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Data collection and variables analyzed

Definitions

Statistical analysis

Results

Discussion

Conflict of interest

Acknowledgments

Diagn Microbiol Infect Dis

Clin Microbiol Infect

Enferm Infecc Microbiol Clin

Int J Infect Dis

J Infect

J Chronic Dis

Enferm Infecc Microbiol Clin

In vitro susceptibilities of Escherichia coli isolated from patients with intra-abdominal infections worldwide in 2002–2004: results from SMART (Study for Monitoring Antimicrobial Resistance Trends)

SurgInfect (Larchmt)

Etiology of community-acquired lower urinary infections and antimicrobial resistance of Escherichia coli: a national surveillance study

Med Clin (Barc)

Increasing prevalence of ESBL-producing Enterobacteriaceae in Europe

Eurosurveillance

Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients

Clin Infect Dis

Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes

Clin Infect Dis

Clinical and economic impact of bacteremia with extended-spectrum-b-lactamase-producing Enterobacteriaceae

Antimicrob Agents Chemother