Microbiologic Response With Linezolid And Vancomycin In Ventilator-Associated Pneumonia Due To Methicillin Resistant Staphylococcus Aureus

Study Overview
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Brief Summary
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Ventilator-associated pneumonia (VAP) is a commonplace complication of intensive care patients ventilated for longer than 48 hours. Methicillin-resistant Staphylococcus aureus (MRSA) is the cause of late onset VAP in up to about 30% of cases in US hospitals. Ineffective treatment of MRSA VAP clearly leads to prolonged mechanical ventilation and is probably associated with higher mortality. The purpose of this protocol is to directly compare linezolid and vancomycin specifically for MRSA VAP.

Official Title
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A Randomized, Open Label, Multi-Center Clinical Trial, Comparing Microbiologic Response To Linezolid And Vancomycin In Ventilator-Associated Pneumonia (VAP) Due To Methicillin Resistant Staphylococcus Aureus (MRSA)

Conditions
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Pneumonia, Ventilator-Associated

Intervention / Treatment
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* Drug: Vancomycin
* Drug: Linezolid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must have or be suspected of having a ventilator-associated pneumonia (VAP) due to MRSA. Patient must be hospitalized for at least 5 days, must be ventilator-dependent ≥ 48 hours prior to screen/baseline, and anticipated to remain on the ventilator for 72 hours after enrollment so follow-up BAL can be performed. Clinical picture compatible with pneumonia (acquired during ventilation) Chest X Ray at baseline/screen or within 24 hours of initiation of therapy must be consistent with diagnosis of pneumonia Exclusion Criteria: Hypersensitivity to linezolid, vancomycin, or one of the excipients in any of these drug formulations. Infections due to gram-positive organisms known to be resistant to either of the study drugs. Any antibiotic used in the treatment of MRSA, such as vancomycin, TMP/SMX, rifampin, or linezolid, for more than 48 hours prior to patient's enrollment into the study. Patients with neutropenia, AIDS, lymphoma or anticipated chemotherapy. Patients who have long-term tracheostomy (for more than 60 days). Acute tracheostomy patients are allowed.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Vancomycin<br>* 1 gram IV every 12 hours for 7 to 14 days<br>|
| Experimental: 2<br> | Drug: Linezolid<br>* 600 mg every 12 hours (intravenously [IV] for a minimum of the first 4 days followed by a switch to oral if tolerated by patient) for a total duration of 7 to 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess early microbiologic response in patients with VAP due to MRSA based on semi-quantitative culture of bronchoscopic bronchoalveolar lavage (BAL) in patients treated with linezolid vs vancomycin. |  | 72-96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare duration of mechanical ventilation |  | 0000 | 
| To compare post treatment tracheal colonization |  | FU: 14 days after EOT +/- 2 days | 
| To identify clinical correlates of infection based on microbiologic sampling as determined by original and modified CPIS (Clinical Pulmonary Infection Score) |  | EOT: Day 14; FU: 14 days after EOT +/- 2 days | 
| To compare the microbiological cure based on BAL specimens with the traditional criteria for microbiologic cure |  | 72-96 hours | 
| To compare mortality at End Of Treatment (EOT) and Follow up (FU); To compare clinical outcome at EOT and FU |  | EOT: Day 14; FU: 14 days after EOT +/- 2 days |