Clinically Significant Bacteremia Clinical Trial
Official title:
Impact of Specific Antimicrobials and Minimal Inhibitory Concentration(MIC) Values on the Outcome of Bloodstream Infections Due to ESBL or Carbapenemase-producing Enterobacteriaceae: an Observational Multinational Study
Main objective: to observationally assess the efficacy of different antimicrobials in
Bloodstream Infection (BSI) due to Enterobacteriaceae producing ESBLs or carbapenemases.
Specific objectives:
Bacteraemic infections due to ESBL-producing Enterobacteriaceae:
- To demonstrate that β-lactam/β-lactam inhibitors are not associated with worse cure
rate and mortality than carbapenems after controlling for confounders, both as
empirical and definitive therapy.
- To demonstrate that fluoroquinolones as definitive therapy are not associated with
worse cure rate and mortality than carbapenems after controlling for confounders.
- To demonstrate that empirical cephalosporins in monotherapy are associated with worse
cure rate and mortality than carbapenems after controlling for confounders in
infections others than urinary tract infections.
- To demonstrate that the association of active aminoglycosides with cephalosporins or
fluoroquinolines is not associated with worse cure rate and mortality than carbapenems
after controlling for confounders.
- To demonstrate that combination empirical and definitive therapy is not associated with
better cure rate than monotherapy after controlling for confounders.
- For tigecycline, colistin, and fosfomycin, no hypothesis. The objective is to provide
adjusted estimations of their association with outcome variables in comparison with
carbapenem monotherapy according to clinical situation and infection.
Bacteraemic infections due to carbapenemase-producing Enterobacteriaceae:
- To demonstrate that combination therapy is associated with worse cure rate and
mortality than monotherapy after controlling for confounders.
- To show that carbapenems are associated with worse cure rate and mortality when used in
infections other than urinary tract caused by isolates showing MIC <2 µg/mL for
imipenem or meropenem in comparison to those caused by isolates with higher MIC, after
controlling for confounders.
- To show that colistin used at a dose >6 million IU per day is associated with improved
outcomes in comparison with lower dose, after controlling for confounders.
METHODS
Study design: multicentre, international retrospective cohort study.
Sites: multiple expert investigators from different countries are invited.
Conditions to fulfil to participate include availability of a database with the required
data or ability to retrospectively collect the data in a timely manner.
Procedure
The participant centres are asked to include:
- Previously published cases: all these cases should be included if possible. The fact
that the case had been previously published should be specified in the database.
- Additionally, participants are asked to include consecutive episodes detected by
reviewing their databases (clinical, infection control or microbiological records) from
January 2004 to June 2012, according to the following criteria:
- For ESBL producers:
A minimum of 20 and a maximum of 50 cases should be included from each centre (the more
recent ones should be selected).
- Cases for which the enzyme is characterised at least to group level by polymerase chain
reaction, PCR, (it is, CTX-M, SHV, TEM) should be prioritised despite the date of
diagnosis.
- If not enough number of cases with PCR-characterized enzymes are available, or
PCR-characterisation has not been performed, the total number of cases should be
completed by including cases in which ESBL-production was identified using a standard
phenotypic method.
- For carbapenemase-producers: only cases in which the carbapenemase was
characterised by PCR should be included. All episodes up to a limit of 50 cases
per centre may be included.
Overall, to avoid selection biases, consecutive cases according to previous criteria should
be included.
Variables
A common online database has been designed. Individual access to the database will be
provided.
Main outcome variable: Cure rate at day 14
Secondary outcome variables: Mortality at 72 hours, 7, 14 and 30 days, clinical improvement
at 72 hours, clinical cure at day 28.
Explanatory variables:
- Demographics
- Severity of chronic underlying conditions: McCabe and Charlson index
- Acute severity of underlying disease: Pitt score during the the day before BSI.
- Type of acquisition
- Source of BSI
- Severity of SIRS at presentation
- Microorganism, betalactamase, MICs
- Empirical therapy
- Definitive therapy
Quality of data. Data will be approved and signed by the responsible investigator in each
center. All data will be centrally reviewed; queries will be sent for lacking data and those
showing inconsistencies or discrepancies. Data will be analysed per center; those with data
showing significant differences with the average will be requested for review.
Statistical Analysis Plan
- Subcohorts with patients treated with the treatment to be compared will be selected.
- A propensity score to receive the 2 treatment types to compare will be calculated by
obtaining a non-parsimonious multivariate model by logistic regression in which the
outcome variable will be the treatment type. The explanatory variables will include
age, gender, center, type of ward, acquisition, Charlson index, Pitt score, severity of
SIRS and source.
- After univariate analysis, multivariate analysis to investigate the adjusted
association of treatment type with the main and secondary outcome variables will be
performed by using logistic regression (for clinical response at day 14) and by Cox
regression for mortality. If time until death is unavailable, logistic regression will
be used for 30-day mortality. Logistic regression will also be used for 72-hour and
30-day clinical response. The propensity score will be added in all cases; also,
Charlson score, Pitt score, severity of SIRS and source will be added. Finally,
interaction between treatment type and source classified as urinary tract and others
will be included.
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Observational Model: Cohort, Time Perspective: Retrospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02852902 -
Impact of Specific Antimicrobials and MIC Values on the Outcome of Bloodstream Infections Due to ESBL- or Carbapenemase-producing Enterobacterales in Solid Organ Transplantation: an Observational Multinational Study.
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