Clinical Outcomes of Linezolid vs Vancomycin in Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia

Background: Vancomycin has been the treatment standard for methicillin-resistant Staphylococcus aureus (MRSA) infections, but clinical efficacy is limited. We report outcomes of a cohort with MRSA ventilator-associated pneumonia (VAP) treated with vancomycin vs linezolid. Methods: Retrospective analysis of 113 participants with MRSA VAP confirmed by bronchoscopy who have been initiated on therapy with either vancomycin or linezolid within 24 hours after bronchoscopy and completed ≥7 days of therapy during their hospitalization from July 2003 to June 2007. The primary endpoints were hospital survival and clinical cure, defined as resolution of signs and symptoms of VAP or microbiological eradication after completion of therapy along with clinical pulmonary infection score (CPIS) ≤6 at day 7 of therapy. Results: At hospital discharge, 23/27 (85.2%) of linezolid and 72/86 (83.7%) of vancomycin recipients had survived (P = .672). In comparison to linezolid recipients, the adjusted odds ratio (OR) for survival was 0.72 (95% confidence interval [CI]: 0.16-3.27) with vancomycin therapy. Clinical cure was achieved in 24/27 (88.9%) of linezolid and 63/86 (73.3%) of vancomycin recipients (P = .066). Compared to linezolid recipients, the adjusted OR for clinical cure was 0.24 (95% CI: 0.05-1.10) with vancomycin therapy. Survival and clinical cure did not differ significantly between vancomycin recipients with trough level ≥15 and <15 μg/mL, respectively. Conclusions: Our results suggested no survival benefit but a trend toward higher cure rate with linezolid therapy. The optimal treatment of MRSA VAP requires further study through randomized, controlled trials.

[1]  G. Drusano,et al.  Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[2]  古谷 良輔,et al.  Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. , 2008, American journal of respiratory and critical care medicine.

[3]  V. Tam,et al.  Risk factors for nephrotoxicity associated with continuous vancomycin infusion in outpatient parenteral antibiotic therapy. , 2008, The Journal of antimicrobial chemotherapy.

[4]  G. Drusano,et al.  Larger Vancomycin Doses (at Least Four Grams per Day) Are Associated with an Increased Incidence of Nephrotoxicity , 2008, Antimicrobial Agents and Chemotherapy.

[5]  M. Furue,et al.  Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant Staphylococcus aureus in Japan. , 2007, The Journal of antimicrobial chemotherapy.

[6]  Joshua A. Doherty,et al.  A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. , 2007, Clinical therapeutics.

[7]  A. Wong-Beringer,et al.  High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. , 2006, Archives of internal medicine.

[8]  Joshua A. Doherty,et al.  Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices. , 2006, Chest.

[9]  Marin H Kollef,et al.  Epidemiology and outcomes of health-care-associated pneumonia: results from a large US database of culture-positive pneumonia. , 2005, Chest.

[10]  R. Wunderink,et al.  Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin , 2004, Intensive Care Medicine.

[11]  R. Wunderink,et al.  Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. , 2003, Chest.

[12]  T. Bauer Nosocomial pneumonia: therapy is just not good enough. , 2003, Chest.

[13]  M. Niederman,et al.  Resolution of ventilator-associated pneumonia: Prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome* , 2003, Critical care medicine.

[14]  J. Rello,et al.  Impact of Gram-positive resistance on outcome of nosocomial pneumonia. , 2001, Critical care medicine.

[15]  Jerome J. Schentag,et al.  Area under the inhibitory curve and a pneumonia scoring system for predicting outcomes of vancomycin therapy for respiratory infections by Staphylococcus aureus. , 2000, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[16]  M. González,et al.  Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[17]  G Sherman,et al.  Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. , 1999, Chest.

[18]  E. Concia,et al.  Penetration of vancomycin into human lung tissue. , 1996, The Journal of antimicrobial chemotherapy.

[19]  J. Rello,et al.  Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. , 1994, American journal of respiratory and critical care medicine.

[20]  R. Farinotti,et al.  Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients , 1993, Antimicrobial Agents and Chemotherapy.

[21]  D. Levine,et al.  Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. , 2009, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[22]  R. Moellering Vancomycin: a 50-year reassessment. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[23]  M. Rybak,et al.  The pharmacokinetic and pharmacodynamic properties of vancomycin. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  Jerome J. Schentag,et al.  Pharmacodynamics of Vancomycin and Other Antimicrobials in Patients with Staphylococcus aureus Lower Respiratory Tract Infections , 2004, Clinical pharmacokinetics.