Clinical trial NCT06370299: Screening of Multidrug Resistant Bacteria, and the Clinical Implication for the Patient
Official title: Screening of Multidrug Resistant Bacteria, and the Implication of a Positive Screening Result Compared to a Negative on Subsequent Infection and Mortality.
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Multi-antibiotic Resistance
Keywords: Multidrug Resistance
Acinetobacter baumannii
Pseudomonas aeruginosa
carbapenem-resistant
gram-negative resistance
ESBL
carbapenemase-producing Enterobacterales
colonization
screening
Lead sponsor: Region Skane
Sponsor class: OTHER
Collaborators: name: Lund University
First posted: 2024-04-17
Enrollment: 10000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Population of Scania region in Sweden consisting of 1.4 million inhabitants. At the time of admission to a hospital in Scania, patients with risk factors for acquisition of MDR undergo screening for MDR carriage. Screenings for MDR are carried out according to local guideline "Suspected MDR - routines for hospitalized patients" and analysed and reported from the one Department of Clinical Microbiology in Lund in Scania region.

Brief summary: The goal of this observational study is to evaluate the screening for multidrug resistant bacteria in patients admitted to hospitals in Scania. The main questions it aims to answer are:

* admission rates after screening
* 30-day and one-year mortality after screening Participants will be evaluated for positive screening results with following multidrug resistant gram negative bacilli: ESBL producing Enterobacterales, Carbapenemase producing Enterobacterales, Carbapenem resistant P.aeruginosa and carbapenem resistant Acinetobacter baumannii. Researchers will compare patients with positive and negative screening results to see, if the relative risks in the two groups differ in admission rates and mortality.

Detailed description: Infections with multidrug resistant bacteria (MDR) cause more than one millions deaths globally according to World Health Organisation. While Scandinavia is still a low-endemic area of resistance compared to other parts of the world, such as South-Asia, South-Europe, a worrisome rise in MDR has been observed in the past decade. Of concern is particularly gram negative bacilli, e.g extended spectrum beta-lactamase (ESBL) and carbapenemase producing Enterobacterales (EPE and CPE) as well as carbapenem resistant Pseudomonas aeruginosa (CRPA) and Acinetobacter baumannii (CRAB). They can cause extremely 'difficult-to-treat' infections, while concomitantly give rise to outbreaks following dissemination in hospital settings for years. Hence patients with risk factors such as contact with health care systems outside of Scandinavia are routinely submitted to MDR screening on admission to hospitals in Scania in Sweden. Resource demanding isolation measures are upheld until negative screening results are reported.

The aim of this study is to evaluate our MDR screening in terms of the clinical course of patients with positive and negative screenings results, respectively.

Primary objective: to compare patients with positive screening results and patients with negative screening results regarding

1. admission rate within a year of screening;
2. occurrence rate of other MDR in clinical samples at the time of screening;
3. 30-day mortality and one-year mortality.

Secondary objective:

1. To evaluate the prevalence of positive screening results;
2. To characterize the MDR species and their phenotypical and genotypical resistance mechanisms;
3. To evaluate prevalence of MDR in clinical samples and time to first occurrence of phenotypically same MDR;
4. To evaluate prevalence of MDR in clinical samples within 30 days in patients with negative screening results.

For relevant primary and secondary outcomes, risk stratifications are performed for total, species and resistance mechanisms.

Methods Study design: population based observational cohort study.

Screening samples are defined as samples collected for purpose of infection prevention and control, and sent for targeted analysis of EPE, CPE, CRPA and CRAB. Following locations are typically screened: rectum/faeces, urine and risk factors such as indwelling catheters, drainage material and wound. Clinical samples are defined as all samples sent for culturing, inherently presumed for suspected infection. Isolates in clinical samples are determined as same as in screening, if they have phenotypically identical susceptibility.

Data collection: All patients included in screening (with negative and positive results) are identified through search in database (LIMS and wwBakt) at Department of Clinical Microbiology, Scania region. Social security numbers are thereafter linked to Regional Patient Register (Informationsplattformen) to collect information on comorbidities, hospital admissions, length of stay, death, antibiotics dispensed in outpatient care in general and specialised practices two weeks prior screening and up till one year after. Antibiotics during inpatient care is also collected. No medical journals will be investigated.

Condition of investigation: patients with positive screening results with following multidrug resistant gram negative bacilli: EPE, CPE, CRPA and CRAB.

"Unexposed" group consists of patients with comparable MDR risk factors but tested negative for EPE, CPE, CRPA and CRAB in screening during study time.

Eligibility criteria: Inclusion Criteria:

* patients with a registered screening for MDR.
* screening performed from October 1st 2013 till December 31st 2022.

Exclusion Criteria:

* carriers of MDR in question before October 1st 2013.
* patients transferred from other regions.

Primary outcomes:
measure: The ratio of the probability of all-cause admission in patients who are screening positive to the probability of all-cause admission in patients who are screening negative.
timeFrame: within one year of screening
measure: The ratio of the probability of death in patients who are screening positive to the probability of death in patients who are screening negative.
timeFrame: 30 days and one year of screening
measure: The ratio of the probability of antibiotic use in patients who are screening positive to the probability of antibiotic use in patients who are screening negative.
timeFrame: within one year of screening
Secondary outcomes:
measure: prevalence of positive screening results
timeFrame: through study completion
measure: prevalence of MDR in clinical samples
timeFrame: through study completion
measure: time to first occurrence of phenotypically same MDR as in screening
timeFrame: through study completion
measure: prevalence of MDR in clinical samples in patients with negative screening results
timeFrame: within 30 days of screening
Other outcomes:
Locations:
Study officials:
affiliation: Region Skane
name: Oskar Ljungquist, M.D PhD
role: PRINCIPAL_INVESTIGATOR
References: