Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06574776
Status:
COMPLETED
Last Update Posted:
None
First Post:
2024-08-23
Brief Title:
Prevalence and Associated Mortality of Infections by Multidrug-Resistant Organisms in Adults Intensive Care Units
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Prevalence and Associated Mortality of Infections by Multidrug-Resistant Organisms in Adults Intensive Care Units in Argentina PREV-AR
Status:
COMPLETED
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PREV-AR
Brief Summary:
Observational 24-hr point prevalence study with longitudinal follow-up at 164 ICUs in Argentina All adult patients aged 18 years at a participating ICU on November 24-28 2023 with 60- day follow-up were included Epidemiological variables sites of infection isolated microorganisms CPE colonisation and hospital characteristics were collected Main outcome measure was ICU mortality
Detailed Description:
Methods Study design PREVAR PREValence of infection by MDR-microorganisms in ARgentina was a national cross-sectional 24-hour multicentre study designed and conducted by SADI and SATI in Argentine ICUs
Participants Sites were recruited to participate via announcements in national meetings official societies websites social media three online meetings explaining the project and emails to all society members Hospitals were registered on a secure website where local investigators recorded main site characteristics in an electronic form
Patient data were entered in an electronic case report form CRF using the Research Electronic Data Capture REDCap database appendix 2 Local researchers were trained through online meetings on how to fill out the CRF A centralized data center was responsible for managing the database and monitoring data quality in close contact with local researchers to minimize the occurrence of missing data A dedicated email address was created to streamline communication
Individual patient data were anonymised by assigning a numerical code to each case and recorded in order of admission
Each local institutional review board approved the study and established the requirement for informed consent
The PREVAR study protocol is available in appendix 3 All adult patients 18 years and older present on a participating ICU on the study day during the 24-h period beginning at 800 am were included The exact date could be selected from November 24-28 2023 to ease logistics for individual sites The patients present on day 1 in the ICU were available for inclusion in the cohort which was then followed for mortality There were no exclusion criteria
Procedures The CRF included baseline and demographic characteristics of the study participants date of hospital and ICU admission age gender comorbid conditions APACHE II and SOFA scores registered on admission risk factors for MDRO infection during the previous six months such as previous admission to a hospital colonisation by Enterobacterales spp only colonisation by CPE was measured as it is the only type of colonisation usually monitored in Argentinian ICUs and antibiotic utilization type of admission medical elective or emergency surgery was also collected Data regarding colonisation by carbapenemase-producing Enterobacterales during the period occurring between hospital admission to enrollment was documented whether colonisation had been detected in the hospital or in the ICU SOFA score was also calculated on the day of enrollment
Patient clinical status regarding infection was recorded by the treating physician according to the SEPSIS-3 definitions as without infection with infection but no sepsis sepsis and septic shock10 In addition infections were considered as definite microbiologically confirmed and probable or possible according to the International Sepsis Forum definitions ISF for pneumonia bloodstream infections including infective endocarditis intravascular catheter-related sepsis intra-abdominal infections urosepsis and surgical wound infections 11 In the cases where culture results were pending categorisation was reviewed with the main investigators when the results were made available Definitions of infection sites were those provided by the ISF 11 Infections were registered as community-acquired ICU-acquired hospital non-ICU acquired or as originating in long term care facilities
According to microbiological findings infections were recorded as MDRO or non-MDRO MDROs of interest were Abaumannii difficult-to treat P aeruginosa carbapenemase-producing enterobacterales extended spectrum β-lactamase producing microorganisms ESBL vancomycin-resistant enterococci and methicillin-resistant S aureus MRSA If available further diagnostic methods were performed to further classified them as KPC carbapenemase-producing enterobacterales KPC metallo-beta-lactamases MBL oxacillinases OXA extended spectrum β-lactamase ESBL producing organisms and AMPC beta-lactamases The group of infections produced by non-MDRO for this study included infections by Spneumoniae Spyogenes Saureus EColi coagulase-negative Staphylococcus Proteus sp KES Klebsiella-Enterobacter-Serratia-Citrobacter KESC group C difficile and others
The prescribed antimicrobial treatment was classified as empiric or targeted according to the presence or not of positive cultures for targeted treatment as adequate or inadequate according to antimicrobial susceptibility testing as utilizing novel or old antibiotics according to the European guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli 12 and as receiving Access Watch and Reserve antibiotic groups according to the AWaRe WHO classification 13 Patients were followed until ICU discharge or death in the ICU
Hospitals were classified as general or specialized and as public or private The number of total hospital beds were recorded as well as ICU beds and the availability of certain relevant resources such as infection control committee and antimicrobial stewardship program Additionally MDRO surveillance for infections and colonisation and how frequently it was performed weekly at ICU admission andor before surgery was detailed Methods used to detect mechanisms of bacterial resistance were recorded as phenotypical molecular or immunochromatographic
The protocol of the study the CRF and all the definitions appear in the Operations Manual appendix 4
Outcomes The main outcome measure was the prevalence of infection by MDRO Secondary outcome measures were overall ICU mortality and its independent determinants 28-day ICU mortality determinants of infections by MDRO prevalence of colonisation by CPE and of infection in general and ICU length of stay Data was censored for 60 days
Statistical analysis Prevalence was calculated as the number of infections caused by MDROs divided by the number of patients in the ICU on the day of the study
Variables are reported as absolute numbers and percentages or as medians and interquartile ranges IQRs Differences in recorded variables between patients with MDRO and non-MDRO infections between survivors and non-survivors and between patients with and without infection were analyzed using the χ² test or Fishers exact test for categorical variables and the t test or Wilcoxon rank-sum test for continuous variables as appropriate
To estimate the associations of patient characteristics ICU organizational factors and hospital characteristics with infection by MDRO and ICU mortality a mixed-effects model was performed These models have a hierarchical structure with patients level 1 nested within hospitals level 2 This nesting accounts for the potential correlation of outcomes within the same hospital Random Effects Hospitals were treated as random effects to account for the potential correlation of outcomes within the same hospital and to capture variability between hospitals through random intercepts Fixed Effects Patient characteristics and ICU organizational factors were included as fixed effects as these are the primary predictors of interest
Only variables with a P value 20 in the bivariable analysis were introduced into the final model The results for fixed effects are reported as odds ratios ORs with 95 confidence intervals CIs Random effects or measures of variation are reported as the variance its standard error SE and the median OR The statistical significance of covariates was determined using the likelihood ratio test
All reported p values are two-sided with a p value 005 considered statistically significant
The funder of the study had no role in study design data collection data analysis data interpretation or writing of the report
Participants Sites were recruited to participate via announcements in national meetings official societies websites social media three online meetings explaining the project and emails to all society members Hospitals were registered on a secure website where local investigators recorded main site characteristics in an electronic form
Patient data were entered in an electronic case report form CRF using the Research Electronic Data Capture REDCap database appendix 2 Local researchers were trained through online meetings on how to fill out the CRF A centralized data center was responsible for managing the database and monitoring data quality in close contact with local researchers to minimize the occurrence of missing data A dedicated email address was created to streamline communication
Individual patient data were anonymised by assigning a numerical code to each case and recorded in order of admission
Each local institutional review board approved the study and established the requirement for informed consent
The PREVAR study protocol is available in appendix 3 All adult patients 18 years and older present on a participating ICU on the study day during the 24-h period beginning at 800 am were included The exact date could be selected from November 24-28 2023 to ease logistics for individual sites The patients present on day 1 in the ICU were available for inclusion in the cohort which was then followed for mortality There were no exclusion criteria
Procedures The CRF included baseline and demographic characteristics of the study participants date of hospital and ICU admission age gender comorbid conditions APACHE II and SOFA scores registered on admission risk factors for MDRO infection during the previous six months such as previous admission to a hospital colonisation by Enterobacterales spp only colonisation by CPE was measured as it is the only type of colonisation usually monitored in Argentinian ICUs and antibiotic utilization type of admission medical elective or emergency surgery was also collected Data regarding colonisation by carbapenemase-producing Enterobacterales during the period occurring between hospital admission to enrollment was documented whether colonisation had been detected in the hospital or in the ICU SOFA score was also calculated on the day of enrollment
Patient clinical status regarding infection was recorded by the treating physician according to the SEPSIS-3 definitions as without infection with infection but no sepsis sepsis and septic shock10 In addition infections were considered as definite microbiologically confirmed and probable or possible according to the International Sepsis Forum definitions ISF for pneumonia bloodstream infections including infective endocarditis intravascular catheter-related sepsis intra-abdominal infections urosepsis and surgical wound infections 11 In the cases where culture results were pending categorisation was reviewed with the main investigators when the results were made available Definitions of infection sites were those provided by the ISF 11 Infections were registered as community-acquired ICU-acquired hospital non-ICU acquired or as originating in long term care facilities
According to microbiological findings infections were recorded as MDRO or non-MDRO MDROs of interest were Abaumannii difficult-to treat P aeruginosa carbapenemase-producing enterobacterales extended spectrum β-lactamase producing microorganisms ESBL vancomycin-resistant enterococci and methicillin-resistant S aureus MRSA If available further diagnostic methods were performed to further classified them as KPC carbapenemase-producing enterobacterales KPC metallo-beta-lactamases MBL oxacillinases OXA extended spectrum β-lactamase ESBL producing organisms and AMPC beta-lactamases The group of infections produced by non-MDRO for this study included infections by Spneumoniae Spyogenes Saureus EColi coagulase-negative Staphylococcus Proteus sp KES Klebsiella-Enterobacter-Serratia-Citrobacter KESC group C difficile and others
The prescribed antimicrobial treatment was classified as empiric or targeted according to the presence or not of positive cultures for targeted treatment as adequate or inadequate according to antimicrobial susceptibility testing as utilizing novel or old antibiotics according to the European guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli 12 and as receiving Access Watch and Reserve antibiotic groups according to the AWaRe WHO classification 13 Patients were followed until ICU discharge or death in the ICU
Hospitals were classified as general or specialized and as public or private The number of total hospital beds were recorded as well as ICU beds and the availability of certain relevant resources such as infection control committee and antimicrobial stewardship program Additionally MDRO surveillance for infections and colonisation and how frequently it was performed weekly at ICU admission andor before surgery was detailed Methods used to detect mechanisms of bacterial resistance were recorded as phenotypical molecular or immunochromatographic
The protocol of the study the CRF and all the definitions appear in the Operations Manual appendix 4
Outcomes The main outcome measure was the prevalence of infection by MDRO Secondary outcome measures were overall ICU mortality and its independent determinants 28-day ICU mortality determinants of infections by MDRO prevalence of colonisation by CPE and of infection in general and ICU length of stay Data was censored for 60 days
Statistical analysis Prevalence was calculated as the number of infections caused by MDROs divided by the number of patients in the ICU on the day of the study
Variables are reported as absolute numbers and percentages or as medians and interquartile ranges IQRs Differences in recorded variables between patients with MDRO and non-MDRO infections between survivors and non-survivors and between patients with and without infection were analyzed using the χ² test or Fishers exact test for categorical variables and the t test or Wilcoxon rank-sum test for continuous variables as appropriate
To estimate the associations of patient characteristics ICU organizational factors and hospital characteristics with infection by MDRO and ICU mortality a mixed-effects model was performed These models have a hierarchical structure with patients level 1 nested within hospitals level 2 This nesting accounts for the potential correlation of outcomes within the same hospital Random Effects Hospitals were treated as random effects to account for the potential correlation of outcomes within the same hospital and to capture variability between hospitals through random intercepts Fixed Effects Patient characteristics and ICU organizational factors were included as fixed effects as these are the primary predictors of interest
Only variables with a P value 20 in the bivariable analysis were introduced into the final model The results for fixed effects are reported as odds ratios ORs with 95 confidence intervals CIs Random effects or measures of variation are reported as the variance its standard error SE and the median OR The statistical significance of covariates was determined using the likelihood ratio test
All reported p values are two-sided with a p value 005 considered statistically significant
The funder of the study had no role in study design data collection data analysis data interpretation or writing of the report
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None