Ventilator-associated Pneumonia (VAP) Diagnostic Stewardship Trial

Implementation of a Diagnostic Stewardship Bundle for Ventilator-associated Pneumonia Among Mechanically-ventilated Patients

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

Study Overview

• Status: Completed
• Conditions: VAP - Ventilator Associated Pneumonia
• Intervention / Treatment: Other: VAP diagnostic stewardship bundle

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.

• Study Type: Interventional
• Enrollment (Actual): 4892
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48170
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria for performance of bronchoalveolar lavage:

  • international normalized ratio (INR)>2,
  • platelet count <50,
  • gross blood in endotracheal secretions,
  • ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2), ratio (P/F ratio)<80,
  • major lung surgery within prior 30 days.

Inclusion Criteria healthcare providers included:

• healthcare providers working in units (CCU and CCMU) as part of routine clinical care.

Exclusion Criteria healthcare providers included:

• healthcare providers that are not as part of routine care in CCU and CCMU

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VAP diagnostic stewardship; Intervention group - all patients hospitalized in study ICUs who were mechanically ventilated Feb 17 2022 - Feb 17 2023.	Other: 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.
No Intervention: 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. While these patients were all mechanically ventilated, their treatment took place prior to the beginning of the study, under what standard or standards of care existed at the time. They received no treatment during the course of the study. No interventions could be assigned because their treatment was performed prior to study start date.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
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.	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
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

Outcome Measure	Measure Description	Time Frame
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	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
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.	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
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. .	During the period of mechanical ventilation (generally ranging between 1-2 days and 1 year).
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

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institutes of Health (NIH); National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Owen Albin, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2022
• Primary Completion (Actual): February 12, 2023
• Study Completion (Actual): March 14, 2023

Study Registration Dates

• First Submitted: November 23, 2021
• First Submitted That Met QC Criteria: January 3, 2022
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Ventilator-associated pneumonia; Antimicrobial stewardship
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Cross Infection; Iatrogenic Disease; Pneumonia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: HUM00203162; 5UL1TR002240-05 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No