Ventilator-associated Pneumonia (VAP) Diagnostic Stewardship Trial

Not Applicable

Completed

Conditions: VAP - Ventilator Associated Pneumonia

Interventions: Other: VAP diagnostic stewardship bundle

Registration Number: NCT05176353

Lead Sponsor: University of Michigan

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 4892

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VAP diagnostic stewardship	VAP diagnostic stewardship bundle	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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. .
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).
Percentage of Respiratory Cultures Obtained by Bronchoalveolar Lavage (BAL)	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
Percentage of Respiratory Cultures From BAL Samples With Alveolar Neutrophils <50% Following Study Intervention.	6 months post-intervention