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Original Research: CRITICAL CARE MEDICINE |

Early Microbiological Response to Linezolid vs Vancomycin in Ventilator-Associated Pneumonia Due to Methicillin-Resistant Staphylococcus aureus

Richard G. Wunderink, MD, FCCP; Meryl H. Mendelson, MD; Michael S. Somero, MD; Timothy C. Fabian, MD; Addison K. May, MD; Helen Bhattacharyya, PhD; Kenneth V. Leeper, Jr., MD, FCCP; Joseph S. Solomkin, MD
Author and Funding Information

*From Northwestern University (Dr. Wunderink), Chicago, IL; Pfizer Inc (Drs. Mendelson and Bhattacharyya), New York, NY; Desert Regional Medical Center (Dr. Somero), Palm Springs, CA; University of Tennessee (Dr. Fabian), Memphis, TN; Vanderbilt University (Dr. May), Nashville, TN; Emory University (Dr. Leeper), Atlanta, GA; University of Cincinnati College of Medicine (Dr. Solomkin), Cincinnati, OH.

Correspondence to: Richard G. Wunderink, MD, FCCP, Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care, 676 N St. Clair, Suite 14–044, Chicago, IL 60611; e-mail: r-wunderink@northwestern.edu


This study was funded by Pfizer Inc. Editorial support was provided by Phil Matthews and Elizabeth Melby Wells at PAREXEL and was funded by Pfizer Inc.

Dr. Wunderink is a paid consultant, is on the speaker's bureau, and has received an investigator-initiated grant from Pfizer. Dr. Mendelson was employed by Pfizer when this study was conducted. She is currently an employee of Novartis Pharmaceuticals (East Hanover, NJ). Dr. Fabian is an investigator for Pfizer. Dr. May is on the speaker's bureau and is an investigator for Pfizer. Dr. Bhattacharyya is an employee of Pfizer. Dr. Leeper is on the speaker's bureau for Pfizer. Drs. Somero and Solomkin have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2008;134(6):1200-1207. doi:10.1378/chest.08-0011
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Background:  Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of ventilator-associated pneumonia (VAP). This prospective, open-label, multicenter clinical trial compared the early microbiological efficacy of linezolid (LZD) therapy with that of vancomycin (VAN) therapy in patients with MRSA VAP.

Methods:  A total of 149 patients with suspected MRSA VAP were randomized to receive either LZD, 600 mg, or VAN, 1 g every 12 h. Patients with baseline bronchoscopic BAL (BBAL) fluid quantitative culture findings that were positive for MRSA (≥ 104 cfu/mL) comprised the study population. The primary outcome was microbiological response (≤ 102 cfu/mL) in a second BBAL performed 72 to 96 h following the start of treatment.

Results:  Thirty LZD-treated patients and 20 VAN-treated patients had microbiologically confirmed MRSA at baseline; 23 and 19 patients, respectively, underwent repeat BBAL. While a greater number of LZD-treated patients than VAN-treated patients achieved a microbiological cure (56.5% vs 47.4%, respectively; p = 0.757; 95% confidence interval, −21.1 to 39.4), this difference was not statistically significant. Nonstatistically significant differences were also seen for LZD-treated patients vs VAN-treated patients in terms of clinical cure (66.7% vs 52.9%, respectively), survival rate (86.7% vs 70.0%, respectively), and the mean duration of ventilation (10.4 vs 14.3 d, respectively), hospitalization (18.8 vs 20.1 d, respectively), ICU stay (12.2 vs 16.2 d, respectively), and time spent alive and not receiving mechanical ventilation (15.5 vs 11.1 d, respectively). Three patients who had been extubated prior to undergoing repeat BBAL had been randomized to receive LZD therapy.

Conclusion:  Early microbiological cure rates were not statistically significantly higher with LZD therapy than with VAN therapy despite trends in all secondary clinical outcomes favoring LZD therapy. These results suggest that any beneficial effect of LZD therapy may be due to factors other than increased bacterial clearance.

Trial registration:  Clinicaltrials.gov Identifier: NCT00572559

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