Clinical trial NCT04616352: Cefuroxime Resistance in Pyelonephritis
Official title: Effect of Inappropriate Therapy With Cefuroxime in Adult Patients Hospitalized With Pyelonephritis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Urinary Tract Infections
Keywords: pyelonephritis
urinary tract infections, complicated
cefuroxime
cephalosporins
Escherichia coli
Drug Resistance, Microbial
Lead sponsor: Universidad Nacional de Colombia
Sponsor class: OTHER
First posted: 2020-11-04
Enrollment: 973
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patiens with ≥ 18 years with a clinical diagnosis of community acquired pyelonephritis that require hospitalization and with positive culture for Escherichia coli.

Brief summary: Resistance to empirical antibiotic treatment has resulted in increased mortality and morbidity in serious infections caused by certain common resistant pathogens in the community. The risk for increased mortality has been also the motivation for recent guidelines that suggest early empirical antimicrobial treatment with broad spectrum antibiotics within a few hours of suspecting sepsis, regardless of the potential microorganism or infection focus. Resistance to second-generation cephalosporins among patients with community-acquired urinary tract infection by E. coli has exceeded 20% in an increasing number of institutions and communities, without being clear about the impact of such resistance on the effectiveness of treatment. This is especially important in urinary infections, since, in general, mortality is very low. We expect to establish if there is a relationship between inappropriate empirical therapy and morbidity (in terms of length of stay or readmission) among hospitalized patients with pyelonephritis treated with empirical cefuroxime therapy to help to define the need for a change in the current guidelines. These guidelines will have application not only in Colombia, but also in other countries in Latin America or other countries that still use this empirical therapy. It will also define the need for use of broader spectrum antibiotics in this clinical scenario.

Detailed description: Objectives:

1. Establish the relationship between inappropriate empirical cefuroxime therapy in adult patients hospitalized with pyelonephritis and hospital stay.
2. Establish the relationship between inappropriate empirical cefuroxime therapy in adult patients hospitalized with pyelonephritis and readmission due to pyelonephritis.
3. Establish the relationship between inappropriate empirical therapy with cefuroxime in adult patients hospitalized with pyelonephritis and the time to readmission caused pyelonephritis.

The investigators proposed a retrospective cohort of hospitalized pyelonephritis patients with empirical antimicrobial management with cefuroxime in one institution of third complexity level. Exposure is understood as resistance to cefuroxime, that is, the impact of inappropriate empirical cefuroxime therapy on patients receiving this antibiotic. Patients who are admitted to the cohort had the diagnosis of pyelonephritis and were hospitalized for intravenous antimicrobial treatment and are followed up to the following outcomes: hospital discharge, or readmission due to pyelonephritis to the same or another institution of the insurance network.

The study will be conducted following the Good Clinical Practices for Research and approval by the Research Ethics Committee (REC) or Investigation Research Boards (IRB) of the participating institutions. The clinical information will be collected through online forms based on the information in the electronic medical record. Microbiological information will be taken from clinical laboratory reports (Whonet ver 5.5., WHO). The accuracy of the information collected will be verified by evaluating 100% of the formats. A pilot test will be carried out after approval by the IRB (25 february, 2020). The information will be stored anonymously, discarding from the database personal information of the patient that might allow the identification. Variables collected from the Electronic Medical Record include demographic, clinical (comorbidities, clinical status) and microbiological information. Other variables include time to change antibiotic (if done) and time of use of antibiotic. Information for the outcomes proposed include length of stay (in days), readmission (new admission because of pyelonephritis in the following 30 days after the first episode), and time to readmission (in days).

A propensity score matching will be performed to diminish the risk of selection bias and unbalanced subjects. Alternatively, and inverse probability treatment weighting can be used to balance the variables included. Both models will be constructed using a logistic regression for the probability of cefuroxime resistant. Final comparison between the exposed population and control population will be done using survival curves for the time to hospital discharge.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years.
* Clinical diagnosis of pyelonephritis.
* Antibiotic treatment with cefuroxime.
* Urine culture positive for Escherichia coli

Exclusion Criteria:

* Use of antibiotic for less than 24 hours.
* Not availability of antimicrobial susceptibility testing.
* Use of urinary catheter for more than 30 days.

Primary outcomes:
measure: Time to hospital discharge
timeFrame: Up to 30 days
measure: Readmission
timeFrame: Up to 30 days after discharge
measure: Time to readmission
timeFrame: Up to 30 days after discharge
Secondary outcomes:
Other outcomes:
Locations:
city: Bogota
country: Colombia
facility: Clínica Reina Sofía
state: DC
Study officials:
affiliation: Univesidad Nacional de Colombia
name: Jorge A Cortes, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nocua-Baez LC, Cortes JA, Leal AL, Arias GF, Ovalle-Guerro MV, Saavedra-Rojas SY, Buitrago G, Escobar-Perez JA, Castro-Cardozo B. [Antimicrobial susceptibility profile in urinary pathogens causing community-acquired infections in diabetic patients in Colombia]. Biomedica. 2017 Sep 1;37(3):353-360. doi: 10.7705/biomedica.v37i3.3348. Spanish.
citation: Leal AL, Cortes JA, Arias G, Ovalle MV, Saavedra SY, Buitrago G, Escobar JA, Castro BE; GREBO. [Emergence of resistance to third generation cephalosporins by Enterobacteriaceae causing community-onset urinary tract infections in hospitals in Colombia]. Enferm Infecc Microbiol Clin. 2013 May;31(5):298-303. doi: 10.1016/j.eimc.2012.04.007. Epub 2012 Jun 15. Spanish.