Early microbiological response to linezolid vs vancomycin in ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus.
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 (>or= 10(4) cfu/mL) comprised the study population. The primary outcome was microbiological response (<or= 10(2) 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.


CONCLUSIONS
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.


BACKGROUND
Clinicaltrials.gov Identifier: NCT00572559.
Wunderink
Richard G
RG
Northwestern University, Chicago, IL. Electronic address: r-wunderink@northwestern.edu.
Mendelson
Meryl H
MH
Pfizer Inc, New York, NY.
Somero
Michael S
MS
Desert Regional Medical Center, Palm Springs, CA.
Fabian
Timothy C
TC
University of Tennessee, Memphis, TN.
May
Addison K
AK
Vanderbilt University, Nashville, TN.
Bhattacharyya
Helen
H
Pfizer Inc, New York, NY.
Leeper
Kenneth V
KV
Emory University, Atlanta, GA.
Solomkin
Joseph S
JS
University of Cincinnati College of Medicine, Cincinnati, OH.
D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069349:Linezolid; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D008875:Middle Aged; D023303:Oxazolidinones / Q000627:therapeutic use*; D053717:Pneumonia, Ventilator-Associated / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D013997:Time Factors; D016896:Treatment Outcome; D014640:Vancomycin / Q000627:therapeutic use*
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid