Duration of Antibiotic Treatment for Early VAP (DATE) Trial (DATE)

A Randomized Clinical Trial of 4 vs. 8 Days of Definitive Antibiotic Therapy for Early Ventilator-Associated Pneumonia in the Surgical Intensive Care Unit

Hypothesis: 4 days of antibiotic therapy, as compared to 8 days, is equally effective and results in decreased antibiotic exposure among surgical ICU patients with early VAP.

Study Overview

• Status: Completed
• Conditions: Early Ventilator Associated Pneumonia
• Intervention / Treatment: Drug: Default 4 days antibiotic therapy

Detailed Description

The prevalence of multi-drug resistant (MDR) pathogens in intensive care units (ICUs) worldwide has reached epidemic proportions. In some cases, the choice of potential therapy is limited or even non-existent. Antibiotic prescription, through selection pressure, represents the main mechanism by which resistance emerges. Limitations in the development of new antibiotics underscores the importance of adherence to the principles of antibiotic stewardship.

Ventilator associated pneumonia (VAP) is the most common serious infection in mechanically ventilated, critically ill patients. Approximately one half of antibiotic prescription in the ICU is related to VAP, including prophylactic, empiric, and definitive therapy. The development of evidence-based algorithms for the rational use of antibiotics in the management of patients with both suspected and confirmed VAP is pivotal to decreasing the emergence of MDR pathogens.

Shortening the duration of antimicrobial therapy for VAP represents one strategy to curtail the emergence of MDR pathogens. Although current guidelines recommend a treatment course of 8-14 days, both clinical and microbiologic resolution (MR) of infection typically occur much sooner [10, 11]. In one study of ICU patients ventilated for > 5 days who developed VAP, 8 days of antimicrobial therapy was equally as effective as 14 days, provided VAP was not caused by a non-lactose fermenting gram negative bacillus. Favorable results following shorter courses of therapy for VAP have been observed, albeit in small, uncontrolled series.

One subset of patients for whom a decreased duration of antimicrobial therapy may be particularly effective is those who develop VAP ≤ 5 days after intubation (early VAP). Early VAP comprises approximately one half of cases of pneumonia diagnosed in the ICU. Furthermore, as compared to patients who develop late VAP, patients who develop early VAP are more likely to be infected with community-acquired pathogens sensitive to narrow spectrum antibiotics. Finally, nearly all cases of early VAP caused by sensitive pathogens demonstrate MR after relatively short (3-5 days) courses of therapy.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Surgical patient
2. VAP, defined as clinical suspicion plus a bronchoalveolar lavage (BAL) culture showing ≥105 cfu/mL of at least one pathogen. The quantitative microbiology threshold will be lowered to ≥104 cfu/mL if the patient was being treated with antibiotics to which the pathogen is sensitive at the time of the BAL. Clinical suspicion of VAP is defined as at least one point for ≥ 2 variables in the Clinical Pulmonary Infection Score (CPIS, described below).
3. Ventilated ≤ 5 days at the time that the BAL was obtained.
4. Hospital LOS ≤ 5 days at the time that the BAL was obtained.

Exclusion Criteria:

1. Age < 18 years.
2. Prior episode of VAP for the index admission (the patient may have had prior BALs sent for culture, but these cannot have met the above mentioned diagnostic criteria for VAP).
3. VAP caused by a MDR pathogen: Early VAP is rarely caused by a MDR pathogen; in a recent analysis of our surgical ICU, 94% of cases of early VAP were caused by a highly sensitive pathogen (MSSA 39%, H flu 35%, S. pneumo 16%, E. coli 9%) (Pieracci in press). Patients with early VAP caused by the following MDR pathogens will be excluded: Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-intermediate Staphylococcus aureus (VISA), pseudomonas aeruginosa, Vancomycin-resistant enterococcus (VRE), Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum beta lactamase producing gram negative bacilli.
4. Antibiotic therapy for ≥ 5 of the last 10 days preceding the BAL.
5. Septic shock, defined as evidence of tissue hypoperfusion after adequate volume expansion, due to infection, and requiring ≥ 1 vasopressor.
6. Current or recent (within 30 days) use of immunosuppressive medications.
7. Length of stay ≥ 48 hours in a transferring facility.
8. Inpatient hospitalization within 30 days of admission.
9. Pregnancy or lactation.
10. Legal arrest or incarceration.

11. Moribund state in which death is imminent.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Default 4 days antibiotic therapy	Drug: Default 4 days antibiotic therapy; The intervention for this trial involves a shorter duration of antibiotic therapy. Specifically, a default of 4 vs. 8 days.; Other Names: Antibiotic for 4 days
No Intervention: Default 8 days antibiotic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response	Clinical Pulmonary Infection Score (CPIS) score. Scales of this score include Temperature, Blood Leukocytes, Tracheal Secretions, Oxygenation, Pulmonary Radiography, and Culture of Tracheal Aspirate. Each scale can have sub-scores ranging from 0-2, with a total CPIS score ranging from 0-12. In this outcome measure, higher scores mean worse functioning and risk for worse outcomes. Scores for the patients analyzed on this outcome measure were taken daily for 28 days and then averaged across that time point.	Daily for 28 days

Collaborators and Investigators

• Sponsor: Denver Health and Hospital Authority

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): November 5, 2021
• Study Completion (Actual): November 5, 2021

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 21, 2013
• First Posted (Estimate): November 26, 2013

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Ventilator-Associated; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 13-0205