Vancomycin De-escalation Therapy in Patients With Pneumonia

Study Overview
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Brief Summary
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This is a non-inferiority study evaluating clinical improvement rate when using MRSA nasal swabs to guide discontinuation of vancomycin for empiric coverage for MRSA pneumonia.

Detailed Description
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Current clinical guidelines recommend including vancomycin in initial empiric therapy if risk factors for MRSA infection are present, or there is a high incidence of MRSA locally. Prolonged exposure to vancomycin, however, has been linked with the risk of vancomycin-associated kidney failure. Studies have reported that a MRSA nasal swab may be used to predict the presence of MRSA pneumonia. Specifically, pneumonia patients with negative MRSA nasal swabs are 95-99% likely to not have pneumonia due to MRSA. There is limited data, however, evaluating the use of a MRSA nasal swab to guide vancomycin therapy. Accordingly, in this study, pneumonia patients in the intervention arm will have empiric vancomycin discontinued following a negative MRSA nasal swab. In the control arm, patients vancomycin will not be discontinued based on the MRSA nasal swab result. The rate of clinical resolution will be compared between these two study arms.

Official Title
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Vancomycin De-escalation Therapy in Patients With Pneumonia and Negative MRSA Nasal Swab

Conditions
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Pneumonia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years old Patients admitted to Charleston Area Medical Center (CAMC) through the Emergency Department who meet the CDC criteria for pneumonia. Nasal surveillance culture for MRSA obtained in the Emergency Department Patients receiving vancomycin and additional antibiotic therapy for gram-negative coverage Exclusion Criteria: Persistent vasopressor requirements when MRSA nasal swab results are available Patients not meeting the CDC criteria for pneumonia Patients presenting to the ED with leukopenia (≤4000) without previous documentation of normal or elevated WBC Patients receiving empiric MRSA antibiotic therapy other than vancomycin for pneumonia Patients with the diagnosis of lung abscess Patients not receiving vancomycin therapy before MRSA nasal swab results are reported Immunocompromised individuals. i.e. patients with AIDS/HIV, vasculitis on immune suppressor therapy, steroid therapy for more than one week prior admission or who received chemotherapy in the last 3 months Patients who do not have a MRSA nasal swab obtained in the ED Nares swab obtained after the completion of the first administered dose of an antibiotic with activity against MRSA Patients with MRSA bacteremia Patients with chronic tracheostomy

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treatment Group A<br>Patients admitted for pneumonia whose MRSA nasal swab is negative for MRSA, and empiric vancomycin is discontinued within 24 hours of the MRSA nasal swab results being documented in the electronic health record. | |
| Treatment Group B<br>Patients admitted for pneumonia whose empiric vancomycin is continued for ≥24 hours after electronic health record documentation of negative MRSA nasal swab results. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Clinical Improvement | Rate of clinical improvement following 7 days of antibiotic therapy for pneumonia. Clinical improvement rate is defined as the percentage of patients who had clinical documentation of improvement or resolution of all clinical signs and symptoms of pneumonia present at the time of pneumonia diagnosis. Afebrile: Temperature <38.0ºC or <100.4ºF Improvement of respiratory symptoms and signs per clinical documentation: cough, dyspnea, tachypnea, purulent sputum, increase respiratory secretions, increased suctioning requirements White blood count (WBC) trending down by at least 25%, or when baseline was≤ 15,000 mm3, or return to the normal values Less oxygen supplementation and ventilation Chest radiographic improvement per radiologist report (e.g. infiltrate, consolidation or cavitation) | Evaluation will be completed 48 hours after 7 days of antibiotic therapy for pneumonia. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital Length of Stay | Date of admission to date of discharge from the hospital | During patient hospital stay for up to 6 months | 
| In-hospital mortality | Number of deaths | During patient hospital stay for up to 6 months | 
| Rate of vancomycin-associated kidney injury defined as a 50% increase in serum creatinine or at least two consecutive increases in serum creatinine by 0.5 mg/dL after at least 48 hours of vancomycin therapy. | Number of kidney injuries following administration of vancomycin | Time between vancomycin administration and discharge from hospital for up to 6 months. | 
| Hospital complications, such as MRSA bacteremia and septic shock | Number of MRSA bacteremia and septic shock patients whose MRSA nasal swab is negative and have MRSA pneumonia | During patient hospital stay for up tp 6 months | 
| Billing cost associated with vancomycin therapy and laboratory monitoring | Total charges associated with vancomycin therapy and laboratory monitoring | During patient hospital stay for up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vancomycin, MRSA nasal swab, Pneumonia