VAP - Ventilator Associated Pneumonia
Conditions
Keywords
Antimicrobial stewardship, Ventilator-associated pneumonia
Brief summary
This is a prospective pilot/feasibility trial of a bundled diagnostic stewardship intervention at the level of the microbiologic testing pathway in ventilator-associated pneumonia (VAP). The study utilized a pre/post design and was initially registered as a single-arm trial because the study intervention could only be applied prospectively to a single group (all patients hospitalized in study ICUs requiring ventilation during the trial intervention period). The study objectives are to safely and effectively reduce antibiotic overuse and its attendant hazards (adverse drug events, Clostridioides difficile diarrhea and generation of multidrug-resistant organisms) among mechanically-ventilated patients. Participating ICUs will have the following three modifications made in their respiratory culture workflows for mechanically-ventilated patients: 1) providers will be required to select a valid indication for respiratory culture performance (worsening ventilator requirements, purulent sputum production, and/or new radiographic infiltrate on chest imaging); 2) respiratory cultures will be preferentially obtained via bronchoscopic or nonbronchoscopic BAL (by respiratory therapists) rather than via endotracheal aspiration; and 3) BAL samples will be sent for cell count and differentials, and respiratory culture results will not be released for samples with \<50% neutrophils. The study will carefully monitor adherence to study interventions, ICU-specific antibiotic utilization rates, and important safety metrics including rates of mortality, ventilator-dependence and ventilator-associated events. The trial hypotheses are: * Implementation of a VAP diagnostic stewardship bundle will be successfully implemented without significant increases in mortality or ventilator-associated events. * Implementation of a VAP diagnostic stewardship bundle will be associated with a reduction in ICU-specific antibiotic utilization rates
Detailed description
Overdiagnosis of ventilator-associated pneumonia (VAP) is common among mechanically-ventilated patients and contributes to antibiotic overuse and the generation of multidrug resistant organisms within intensive care units (ICUs). Identification of interventions that safely and effectively lower VAP overdiagnosis and antibiotic overuse are important for antimicrobial stewardship programs. Antibiotic stewardship interventions targeting VAP have heretofore focused on therapeutic interventions-antibiotic de-escalation or discontinuation-in established VAP cases, but have not leveraged interventions at the level of the VAP diagnostic testing pathway to minimize overdiagnosis in the first place. Current microbiologic testing practices-specifically, indiscriminate ordering, collection and interpretation of respiratory cultures-incents VAP overdiagnosis and antibiotic overuse. This is a prospective pilot/feasibility trial of a bundled diagnostic stewardship intervention targeting the microbiologic diagnostic testing pathway among mechanically-ventilated patients. The study utilized a pre/post design and was initially registered as a single-arm trial because the study intervention could only be applied prospectively to a single group (all patients hospitalized in study ICUs requiring ventilation during the trial intervention period). This pilot/feasibility trial will implement system-based changes within ICUs in microbiologic diagnostic testing workflows with the goal of safely lowering antibiotic utilization rates in mechanically-ventilated patients. Specifically, the study will sequentially implement the following 3 changes in the diagnostic testing workflow for clinical providers: 1. Ordering respiratory cultures: 1. Current workflow: respiratory cultures can be ordered by frontline clinical providers without preconditions. 2. Study intervention: frontline clinical providers will be required to select a valid indication for respiratory culture collection through a custom order set in the institutional electronic medical record (EMR). 2. Collection of respiratory cultures: 1. Current workflow: providers may collect endotracheal aspirates (proximal lung secretions) or bronchoalveolar lavage (distal lung secretions) for analysis. 2. Study intervention: providers will be required to preferentially use only bronchoalveolar lavage (BAL) to minimize false positive test results (assuming no contraindications to BAL performance). This will be accomplished through a custom order set in the institutional EMR. 3. Reporting of respiratory cultures: 1. Current workflow: positive respiratory culture results are automatically released in the EMR, regardless of likelihood of infection. 2. Study intervention: respiratory culture results will be automatically released in the EMR only for BAL samples with a polymorphonuclear (PMN) percentage of \>50% (to minimize false positive test results). Respiratory culture results for BAL samples with PMN% \<50% will be released if the primary team calls the microbiology lab directly and requests result release. All proposed interventions are within the standard of care for routine clinical practice, but have not been operationalized in parallel to each other and studied explicitly with the goal of reducing antibiotic overuse. The first two study interventions will be implemented at the beginning of the trial period and the final study intervention will be implemented 6 months after. The interventions will be operationalized through use of a custom order set in the institutional EMR and modifications to Clinical Microbiology Laboratory Workflows, as well as through bimonthly provider educational sessions performed by study personnel during morning ICU rounds. Use of the clinical decision support tool within the EMR by frontline providers will be entirely volitional. The study population in this trial includes all patients admitted to participating study ICUs for routine clinical care. Providers will engage in routine clinical care utilizing the aforementioned modified diagnostic testing workflows and the study will compare safety outcomes and ICU antibiotic utilization rates pre- and post-intervention implementation. Healthcare providers in participating ICUs will provide routine clinical care utilizing these novel diagnostic testing workflows. Adherence to study interventions by these healthcare providers will be assessed during this study to inform project feasibility on a larger scale.
Interventions
OTHERVAP diagnostic stewardship bundle
Multifaceted VAP diagnostic stewardship bundle targeting the respiratory culture testing workflow through a custom order set within the institutional electronic medical record. Interventions will be made at the three levels of the diagnostic testing pathway (ordering, collection and reporting of test results). Full details available in detailed study description.
Sponsors
National Institutes of Health (NIH)
National Center for Advancing Translational Sciences (NCATS)
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Masking description
Due to the nature of this pilot trial the study will obtain an exemption from informed consent.
Intervention model description
Implementation of a VAP diagnostic stewardship bundled intervention targeting ordering, collection and reporting results of respiratory cultures among mechanically-ventilated patients. Interventions will be implemented through a custom order set within the institutional electronic medical record in 2-month sequential intervals. Safety, ICU-specific antibiotic utilization rates and adherence to study interventions will be monitored.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Patients included: * All patients hospitalized within the Michigan Medicine Cardiac Care Unit (CCU, 7D) and the Michigan Medicine Critical Care Medicine Unit (CCMU, 6D)
Exclusion criteria
Patients included: * For the study intervention requiring performance of bronchoalveolar lavage rather than endotracheal aspirate for respiratory culture collection, the following are
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Deaths in the Pre vs Post-intervention Time Periods Among Study Participants Per 1000 Mechanically Ventilated Patient Days | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | The number of deaths that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period. |
| Change in Ventilator-associated Events (V-A Events) (Using Centers for Disease Control/National Healthcare Safety Network Definitions) Per 1000 Patient Days | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | The change in ventilator-associated events that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation, as shown by comparing pre-intervention data to post-intervention data. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period. |
| Median Duration of Mechanical Ventilation Per Patient | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Respiratory Cultures Ordered Per 1000 Mechanically-ventilated Patient Days | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | — |
| Number of Positive Respiratory Cultures (RCs) Per 1,000 Mechanically-ventilated Patient Days (MVPDs) | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | Positive respiratory cultures were defined as any respiratory culture growing a bacterial organism, regardless of total colony-forming units/mL |
| Percentage of Respiratory Cultures From BAL Samples With Alveolar Neutrophils <50% Following Study Intervention. | 6 months post-intervention | — |
| Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL) | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | — |
| Total ICU Antibiotic Utilization Rates | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | Rates are shown as total antibiotic days of therapy per 1000 mechanically-ventilated patient days. A Day of therapy is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy. |
| Broad-spectrum ICU Antibiotic Utilization Rates | During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year). | Utilization rates are shown as broad-spectrum antibiotic days of therapy per 1000 mechanically-ventilated patient days. Broad-spectrum antibiotics were defined as antibiotics with expected coverage against methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. A day of therapy is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy. . |
Countries
United States
Participant flow
Pre-assignment details
The entire study operated under waiver of consent. There was no assignment to the historical control arm. Rather, there was a collection of data retrospectively from persons on ventilators during the five-year period preceding the intervention period.
Participants by arm
| Arm | Count |
|---|---|
| Pre-VAP Diagnostic Stewardship Pre-intervention historical control group - all patients hospitalized in study ICUs who were mechanically ventilated Feb 17, 2017- Feb 16, 2022. | 4,205 |
| VAP Diagnostic Stewardship Intervention group - all patients hospitalized in study ICUs who were mechanically ventilated Feb 17, 2022 - Feb 17, 2023.
VAP diagnostic stewardship bundle: Multifaceted VAP diagnostic stewardship bundle targeting the respiratory culture testing workflow through a custom order set within the institutional electronic medical record. Interventions will be made at the three levels of the diagnostic testing pathway (ordering, collection and reporting of test results). Full details available in detailed study description. | 687 |
| Total | 4,892 |
Baseline characteristics
| Characteristic | Pre-VAP Diagnostic Stewardship | VAP Diagnostic Stewardship | Total |
|---|---|---|---|
| Age, Continuous | 58.7 years STANDARD_DEVIATION 16.2 | 57.8 years STANDARD_DEVIATION 16.8 | 58.6 years STANDARD_DEVIATION 16.27 |
| Race/Ethnicity, Customized Black | 609 Participants | 103 Participants | 712 Participants |
| Race/Ethnicity, Customized Other | 293 Participants | 67 Participants | 360 Participants |
| Race/Ethnicity, Customized White | 3303 Participants | 517 Participants | 3820 Participants |
| Region of Enrollment United States | 4205 Participants | 687 Participants | 4892 Participants |
| Sex: Female, Male Female | 1705 Participants | 277 Participants | 1982 Participants |
| Sex: Female, Male Male | 2500 Participants | 410 Participants | 2910 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1,666 / 4,205 | 284 / 687 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 278 / 4,205 | 34 / 687 |
Outcome results
Primary
Change in Ventilator-associated Events (V-A Events) (Using Centers for Disease Control/National Healthcare Safety Network Definitions) Per 1000 Patient Days
The change in ventilator-associated events that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation, as shown by comparing pre-intervention data to post-intervention data. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period.
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Change in Ventilator-associated Events (V-A Events) (Using Centers for Disease Control/National Healthcare Safety Network Definitions) Per 1000 Patient Days | 15 V-A events per 1000 pt days |
| VAP Diagnostic Stewardship | Change in Ventilator-associated Events (V-A Events) (Using Centers for Disease Control/National Healthcare Safety Network Definitions) Per 1000 Patient Days | 10 V-A events per 1000 pt days |
p-value: 0.05Z-score test for person-time rates
Primary
Median Duration of Mechanical Ventilation Per Patient
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Median Duration of Mechanical Ventilation Per Patient | 3 Calendar Days |
| VAP Diagnostic Stewardship | Median Duration of Mechanical Ventilation Per Patient | 3 Calendar Days |
p-value: 0.59Kruskal-Wallis
Primary
Total Number of Deaths in the Pre vs Post-intervention Time Periods Among Study Participants Per 1000 Mechanically Ventilated Patient Days
The number of deaths that occur across the entire study population will be divided by every 1000 days that the total number of patients were hospitalized in study ICUs, receiving mechanical ventilation. Data was collected retrospectively for 5 years prior to the intervention and for 1 year during the intervention period.
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Total Number of Deaths in the Pre vs Post-intervention Time Periods Among Study Participants Per 1000 Mechanically Ventilated Patient Days | 72 Deaths per 1000 patient-days |
| VAP Diagnostic Stewardship | Total Number of Deaths in the Pre vs Post-intervention Time Periods Among Study Participants Per 1000 Mechanically Ventilated Patient Days | 73 Deaths per 1000 patient-days |
p-value: 0.86Z-score test for person-time rates
Secondary
Broad-spectrum ICU Antibiotic Utilization Rates
Utilization rates are shown as broad-spectrum antibiotic days of therapy per 1000 mechanically-ventilated patient days. Broad-spectrum antibiotics were defined as antibiotics with expected coverage against methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa. A day of therapy is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy. .
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Broad-spectrum ICU Antibiotic Utilization Rates | 1199 days of therapy per 1000 patient-days |
| VAP Diagnostic Stewardship | Broad-spectrum ICU Antibiotic Utilization Rates | 1149 days of therapy per 1000 patient-days |
p-value: 0.03Z-score test for person-time rates
Secondary
Number of Positive Respiratory Cultures (RCs) Per 1,000 Mechanically-ventilated Patient Days (MVPDs)
Positive respiratory cultures were defined as any respiratory culture growing a bacterial organism, regardless of total colony-forming units/mL
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Number of Positive Respiratory Cultures (RCs) Per 1,000 Mechanically-ventilated Patient Days (MVPDs) | 127 positive RCs per 1,000 MVPDs |
| VAP Diagnostic Stewardship | Number of Positive Respiratory Cultures (RCs) Per 1,000 Mechanically-ventilated Patient Days (MVPDs) | 102 positive RCs per 1,000 MVPDs |
p-value: <0.01Z-score test for person-time rates
Secondary
Number of Respiratory Cultures Ordered Per 1000 Mechanically-ventilated Patient Days
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Number of Respiratory Cultures Ordered Per 1000 Mechanically-ventilated Patient Days | 334 Cultures ordered per 1000 patient-days |
| VAP Diagnostic Stewardship | Number of Respiratory Cultures Ordered Per 1000 Mechanically-ventilated Patient Days | 268 Cultures ordered per 1000 patient-days |
p-value: <0.01Z-score test for person-time rates
Secondary
Percentage of Respiratory Cultures From BAL Samples With Alveolar Neutrophils <50% Following Study Intervention.
Time frame: 6 months post-intervention
Population: This outcome measure only applied to the post-intervention arm. This was an optional test that providers could order, but many providers cancelled the test. Thus few BAL cell count/differentials were sent.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Percentage of Respiratory Cultures From BAL Samples With Alveolar Neutrophils <50% Following Study Intervention. | 4.3 Percentage of respiratory cultures |
Secondary
Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL)
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
Population: Some providers ordered more than one culture per patient over the course of their hospital stay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL) | 53.1 percentage of respiratory cultures |
| VAP Diagnostic Stewardship | Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL) | 56.9 percentage of respiratory cultures |
p-value: 0.05Chi-squared
Secondary
Total ICU Antibiotic Utilization Rates
Rates are shown as total antibiotic days of therapy per 1000 mechanically-ventilated patient days. A Day of therapy is defined as a calendar day in which a patient received a systemically-administered antibiotic, regardless of dose. Receipt of multiple, unique antibiotics on a given calendar day were counted cumulatively, that is, if a patient received 3 unique antibiotics that was counted as three days of therapy.
Time frame: During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pre-VAP Diagnostic Stewardship | Total ICU Antibiotic Utilization Rates | 1361 days of therapy per 1000 patient-days |
| VAP Diagnostic Stewardship | Total ICU Antibiotic Utilization Rates | 1335 days of therapy per 1000 patient-days |
p-value: 0.2Z-score test for person-time rates