Methicillin-resistant Staphylococcus Aureus
Conditions
Keywords
MRSA infection
Brief summary
The Randomized Evaluation of Decolonization versus Universal Clearance to Eliminate MRSA (REDUCE MRSA) Trial is a cluster randomized trial of the comparative effectiveness of three strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) in intensive care units. The three strategies to be evaluated are: * screening on admission followed by isolation of MRSA+ patients * screening on admission followed by isolation and decolonization of MRSA+ patients * universal decolonization on admission with no screening. The decolonization regimen involves bathing with chlorhexidine plus intra-nasal application of mupirocin. The main outcome will be MRSA+ clinical cultures. The study is a partnership between the CDC, the CDC Prevention Epicenters, and the Hospital Corporation of America.
Detailed description
Baseline data involving 12 months of data for participating hospitals (July 2008 - June 2009) was collected prior to randomization to account for size and ICU baseline prevalence of MRSA in randomization scheme. Randomization occurred at the hospital level. Eligibility survey was conducted to determine exclusion criteria. As of May 2010, enrollment has been closed. 45 hospitals were randomized, but two were found to meet exclusion criteria and were excluded. As-randomized (or as-assigned) analysis included 43 hospitals, representing 74 ICUs. Individual (patient-level) subject enrollment during intervention is 74,256.
Interventions
DRUGChlorhexidine bath and nasal mupirocin
The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US - a combination of daily baths with 2% chlorhexidine cloths , plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily)
Sponsors
Agency for Healthcare Research and Quality (AHRQ)
Centers for Disease Control and Prevention
Hospital Corporation of America
University of California, Irvine
Department of Population Medicine, Harvard Medical School / Harvard Pilgrim Healthcare Institute
Harvard Pilgrim Health Care
Study design
Allocation
RANDOMIZED
Primary purpose
PREVENTION
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Inclusion criteria will include all HCA hospitals that reside in US states where physicians do NOT routinely prescribe decolonization for MRSA + ICU patients.
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Main Outcome: Patients With Nosocomial MRSA Clinical Cultures | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | Hazard ratio for ICU-attributable MRSA+ clinical cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU-attributable All-pathogen Bloodstream Infection | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | Hazard ratio for ICU-attributable positive blood culture from any pathogen, comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. |
| Intervention Impact on Healthcare Costs | 12-month period | Costs (in dollars) per 1000 ICU-admissions associated with 3 ICU strategies to reduce ICU Bloodstream infection (BSI), (Arms 1-3). |
| Blood Culture Contamination Rates | 24-month time frame for this analysis represents a 6-month baseline and 18-month intervention period. | Odds ratio for ICU-attributable blood culture contamination rates, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital. |
| MRSA Bloodstream Infection | The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge. | Hazard ratio for ICU-attributable MRSA+ blood cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital. |
| Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | 25-month time frame represents 7-month baseline and 18-month intervention periods | Odds ratio for MRSA+ isolates from ICU patients expressing low-level mupirocin resistance (LLMR) and high-level mupirocin resistance (HLMR), comparing baseline to intervention period across arms, accounting for clustering by hospital. |
| Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates | 25-month time frame represents 7-month baseline and 18-month intervention periods | Frequency of MRSA+ isolates from ICU patients with reduced susceptibility to chlorhexidine (CHG) (MIC \>4 μg/ml), comparing baseline to intervention period across arms, accounting for clustering by hospital. |
| Intervention Impact on Bacteriuria and Candiduria | 30-month time frame represents 12-month baseline and 18-month intervention periods. | Proportional hazard ratio for as-randomized, unadjusted, ICU-attributable bacteriuria, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital. High-level bacteriuria is defined as ≥50,000 CFU/mL, high-level candiduria is defined as ≥50,000 CFU/mL. |
Countries
United States
Participant flow
Recruitment details
45 out of 165 Hospital Corporation of America (HCA) hospitals were recruited for this trial of adult ICUs. There was a 12-month baseline period from January 1 through December 31, 2009; a phase-in period from January 1 through April 7, 2010; and an 18-month intervention period from April 8, 2010 through September 30, 2011.
Pre-assignment details
74,256 patients were involved in the intervention period among adult ICUs from the 43 participating hospitals. Routinely collected information for about 48,390 individuals cared for during the baseline period was used for comparison to the experience of the patients in all three arms of the Intervention period.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Usual Care-Active Surveillance Active Surveillance in All Adult ICUs, Contact Precautions for MRSA+ | 39,296 |
| Arm 2: Targeted Decolonization Continue Active Surveillance (AS), MRSA decolonization based on AS, Continue Contact Precautions for MRSA+
Chlorhexidine bath and nasal mupirocin: The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US - a combination of daily baths with 2% chlorhexidine cloths plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily) | 39,970 |
| Arm 3: Universal Decolonization Chlorhexidine bath and nasal mupirocin for all, Discontinuation of Active Surveillance, Contact Precautions for MRSA+
Chlorhexidine bath and nasal mupirocin: The intervention / decolonization regimen will consist of the most commonly used topical regimen in the US - a combination of daily baths with 2% chlorhexidine cloths plus 5 days of topical intranasal mupirocin ointment (bilateral nares, twice daily) | 43,380 |
| Total | 122,646 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Hospital | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1: Usual Care-Active Surveillance | Arm 2: Targeted Decolonization | Arm 3: Universal Decolonization | Total |
|---|---|---|---|---|
| Age, Continuous Baseline Age | 65 Years | 66 Years | 65 Years | 65 Years |
| Age, Continuous Intervention Age | 65 Years | 66 Years | 65 Years | 65 Years |
| Overall Number of Participants, by Phase Baseline Participants | 15816 Admissions | 15218 Admissions | 17356 Admissions | 48390 Admissions |
| Overall Number of Participants, by Phase Intervention Participants | 23480 Admissions | 24752 Admissions | 26024 Admissions | 74256 Admissions |
| Sex/Gender, Customized Females - Baseline | 7465 participants | 7183 participants | 8314 participants | 22962 participants |
| Sex/Gender, Customized Females - Intervention | 11176 participants | 11683 participants | 12361 participants | 35220 participants |
| Sex/Gender, Customized Males - Baseline | 8351 participants | 8035 participants | 9042 participants | 25428 participants |
| Sex/Gender, Customized Males - Intervention | 12304 participants | 13069 participants | 13663 participants | 39036 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 23,480 | 2 / 24,752 | 5 / 26,024 |
| serious Total, serious adverse events | 0 / 23,480 | 0 / 24,752 | 0 / 26,024 |
Outcome results
Primary
Main Outcome: Patients With Nosocomial MRSA Clinical Cultures
Hazard ratio for ICU-attributable MRSA+ clinical cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
Time frame: The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge.
Population: The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Main Outcome: Patients With Nosocomial MRSA Clinical Cultures | 0.92 hazard ratio |
| Arm 2: Targeted Decolonization | Main Outcome: Patients With Nosocomial MRSA Clinical Cultures | 0.75 hazard ratio |
| Arm 3: Universal Decolonization | Main Outcome: Patients With Nosocomial MRSA Clinical Cultures | 0.63 hazard ratio |
p-value: 0.01Proportional-hazards models
Secondary
Blood Culture Contamination Rates
Odds ratio for ICU-attributable blood culture contamination rates, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital.
Time frame: 24-month time frame for this analysis represents a 6-month baseline and 18-month intervention period.
Population: The number of participants analyzed reflects the combined total of baseline and intervention admissions, with an ICU stay and a blood draw set, for each arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Blood Culture Contamination Rates | As randomized, unadjusted | 0.74 Odds Ratio |
| Arm 1: Usual Care-Active Surveillance | Blood Culture Contamination Rates | As randomized, adjusted | 0.73 Odds Ratio |
| Arm 2: Targeted Decolonization | Blood Culture Contamination Rates | As randomized, unadjusted | 0.94 Odds Ratio |
| Arm 2: Targeted Decolonization | Blood Culture Contamination Rates | As randomized, adjusted | 0.93 Odds Ratio |
| Arm 3: Universal Decolonization | Blood Culture Contamination Rates | As randomized, unadjusted | 0.56 Odds Ratio |
| Arm 3: Universal Decolonization | Blood Culture Contamination Rates | As randomized, adjusted | 0.55 Odds Ratio |
Secondary
ICU-attributable All-pathogen Bloodstream Infection
Hazard ratio for ICU-attributable positive blood culture from any pathogen, comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
Time frame: The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge.
Population: The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Usual Care-Active Surveillance | ICU-attributable All-pathogen Bloodstream Infection | 0.99 Hazard ratio |
| Arm 2: Targeted Decolonization | ICU-attributable All-pathogen Bloodstream Infection | 0.78 Hazard ratio |
| Arm 3: Universal Decolonization | ICU-attributable All-pathogen Bloodstream Infection | 0.56 Hazard ratio |
Secondary
Intervention Impact on Bacteriuria and Candiduria
Proportional hazard ratio for as-randomized, unadjusted, ICU-attributable bacteriuria, comparing Baseline to Intervention period across Arms, accounting for clustering by hospital. High-level bacteriuria is defined as ≥50,000 CFU/mL, high-level candiduria is defined as ≥50,000 CFU/mL.
Time frame: 30-month time frame represents 12-month baseline and 18-month intervention periods.
Population: The number of participants analyzed reflects the combined total of baseline and intervention admissions with an ICU stay, for each arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (all patients) | 1.14 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (men) | 1.01 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (men) | 1.21 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (women) | 1.09 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (all patients) | 1.02 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (women) | .91 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (men) | 1.09 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (women) | 0.97 Hazard Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (all patients) | .95 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (women) | 1.00 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (all patients) | 0.88 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (women) | 0.83 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (men) | 1.01 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (all patients) | .99 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (men) | 1.01 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (all patients) | .92 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (women) | .86 Hazard Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (men) | 1.04 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (men) | .78 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (all patients) | 0.87 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (all patients) | .86 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level bacteriuria (women) | 0.93 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (men) | .74 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (women) | .94 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (all patients) | .83 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | Any bacteriuria (women) | .95 Hazard Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Bacteriuria and Candiduria | High-level candiduria (men) | .63 Hazard Ratio |
Secondary
Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates
Frequency of MRSA+ isolates from ICU patients with reduced susceptibility to chlorhexidine (CHG) (MIC \>4 μg/ml), comparing baseline to intervention period across arms, accounting for clustering by hospital.
Time frame: 25-month time frame represents 7-month baseline and 18-month intervention periods
Population: The total number of participants analyzed reflects the combined total of baseline and intervention participants during the outcome time frame, for each arm. The total number of units analyzed reflects the combined total of MRSA+ isolates collected from ICU patients during baseline and intervention phase, for each arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates | 2 MRSA isolates non-susceptible to CHG |
| Arm 2: Targeted Decolonization | Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates | 0 MRSA isolates non-susceptible to CHG |
| Arm 3: Universal Decolonization | Intervention Impact on Chlorhexidine Susceptibility of MRSA Isolates | 0 MRSA isolates non-susceptible to CHG |
Secondary
Intervention Impact on Healthcare Costs
Costs (in dollars) per 1000 ICU-admissions associated with 3 ICU strategies to reduce ICU Bloodstream infection (BSI), (Arms 1-3).
Time frame: 12-month period
Population: Annual adult ICU admissions per hospital, over the course of 1 year.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Healthcare Costs | Cost of MRSA screening tests | 9,120 Dollars per 1000 ICU-admissions |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Healthcare Costs | Cost of contact precautions | 69,010 Dollars per 1000 ICU-admissions |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Healthcare Costs | Cost of decolonization | 0 Dollars per 1000 ICU-admissions |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Healthcare Costs | ICU costs (not including intervention costs) | 19,320,000 Dollars per 1000 ICU-admissions |
| Arm 2: Targeted Decolonization | Intervention Impact on Healthcare Costs | ICU costs (not including intervention costs) | 19,250,000 Dollars per 1000 ICU-admissions |
| Arm 2: Targeted Decolonization | Intervention Impact on Healthcare Costs | Cost of MRSA screening tests | 9,120 Dollars per 1000 ICU-admissions |
| Arm 2: Targeted Decolonization | Intervention Impact on Healthcare Costs | Cost of decolonization | 4,679 Dollars per 1000 ICU-admissions |
| Arm 2: Targeted Decolonization | Intervention Impact on Healthcare Costs | Cost of contact precautions | 68,830 Dollars per 1000 ICU-admissions |
| Arm 3: Universal Decolonization | Intervention Impact on Healthcare Costs | ICU costs (not including intervention costs) | 19,170,000 Dollars per 1000 ICU-admissions |
| Arm 3: Universal Decolonization | Intervention Impact on Healthcare Costs | Cost of contact precautions | 24,890 Dollars per 1000 ICU-admissions |
| Arm 3: Universal Decolonization | Intervention Impact on Healthcare Costs | Cost of decolonization | 36,500 Dollars per 1000 ICU-admissions |
| Arm 3: Universal Decolonization | Intervention Impact on Healthcare Costs | Cost of MRSA screening tests | 0 Dollars per 1000 ICU-admissions |
Secondary
Intervention Impact on Mupirocin Susceptibility of MRSA Isolates
Odds ratio for MRSA+ isolates from ICU patients expressing low-level mupirocin resistance (LLMR) and high-level mupirocin resistance (HLMR), comparing baseline to intervention period across arms, accounting for clustering by hospital.
Time frame: 25-month time frame represents 7-month baseline and 18-month intervention periods
Population: The total number of participants analyzed reflects the combined total of baseline and intervention participants during the outcome time frame, for each arm. The total number of units analyzed reflects the combined total of MRSA+ isolates collected from ICU patients during baseline and intervention phase, for each arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: LLMR | 1.0 Odds Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: HLMR | 0.8 Odds Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: LLMR | 1.7 Odds Ratio |
| Arm 1: Usual Care-Active Surveillance | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: HLMR | 1.5 Odds Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: HLMR | 0.7 Odds Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: LLMR | 1.4 Odds Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: LLMR | 0.4 Odds Ratio |
| Arm 2: Targeted Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: HLMR | 0.9 Odds Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: HLMR | 1.4 Odds Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: HLMR | 0.7 Odds Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | ICU-attributable MRSA: LLMR | 0.7 Odds Ratio |
| Arm 3: Universal Decolonization | Intervention Impact on Mupirocin Susceptibility of MRSA Isolates | Clinical MRSA: LLMR | 0.5 Odds Ratio |
Secondary
MRSA Bloodstream Infection
Hazard ratio for ICU-attributable MRSA+ blood cultures comparing Baseline to Intervention period, by Arm, accounting for clustering by hospital.
Time frame: The 30-month time frame represents 12-month baseline and 18-month intervention periods. During these time periods, outcomes are defined as events occurring during attributed ICU time: from day 3 of the ICU stay until 2 days after ICU discharge.
Population: The total number of participants analyzed included the table reflects the combined total of baseline and intervention participants, for each arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Usual Care-Active Surveillance | MRSA Bloodstream Infection | 1.23 hazard ratio |
| Arm 2: Targeted Decolonization | MRSA Bloodstream Infection | 1.23 hazard ratio |
| Arm 3: Universal Decolonization | MRSA Bloodstream Infection | 0.72 hazard ratio |