Intensive Care Medicine

, Volume 30, Issue 3, pp 388–394 | Cite as

Clinical cure and survival in Gram-positive ventilator-associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin

  • Marin H. Kollef
  • Jordi Rello
  • Sue K. Cammarata
  • Rodney V. Croos-Dabrera
  • Richard G. Wunderink
Original

Abstract

Objective

To assess the effect of baseline variables, including treatment, on clinical cure and survival rates in patients with Gram-positive, ventilator-associated pneumonia (VAP).

Design

Retrospective analysis of two randomized, double-blind studies.

Setting

Multinational study with 134 sites.

Patients

544 patients with suspected Gram-positive VAP, including 264 with documented Gram-positive VAP and 91 with methicillin-resistant S. aureus (MRSA) VAP.

Interventions

Linezolid 600 mg or vancomycin 1 g every 12 h for 7–21 days, each with aztreonam.

Measurements and results

Clinical cure rates assessed 12–28 days after the end of therapy and excluding indeterminate or missing outcomes significantly favored linezolid in the Gram-positive and MRSA subsets. Logistic regression showed that linezolid was an independent predictor of clinical cure with odds ratios of 1.8 for all patients, 2.4 for Gram-positive VAP, and 20.0 for MRSA VAP. Kaplan-Meier survival rates favored linezolid in the MRSA subset. Logistic regression showed that linezolid was an independent predictor of survival with odds ratios of 1.6 for all patients, 2.6 for Gram-positive VAP, and 4.6 for MRSA VAP.

Conclusions

Initial linezolid therapy was associated with significantly better clinical cure and survival rates than was initial vancomycin therapy in patients with MRSA VAP.

Keywords

Linezolid Vancomycin Gram-positive pneumonia Methicillin-resistant Staphylococcus aureus Mechanical ventilation Regression analysis 

References

  1. 1.
    Kollef MH, Sherman G, Ward S, Fraser VJ (1999) Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 115:462–474PubMedGoogle Scholar
  2. 2.
    Dupont H, Mentec H, Sollet JP, Bleichner G (2001) Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia. Intensive Care Med 27:355–362Google Scholar
  3. 3.
    Rubinstein E, Cammarata S, Oliphant T, Wunderink R (2001) Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study. Clin Infect Dis 32:402–412CrossRefPubMedGoogle Scholar
  4. 4.
    Wunderink RG, Cammarata SK, Oliphant TH, Kollef MH (2003) Linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia: continuation of a randomized, double-blind, multicenter study. Clin Ther 25:980–992CrossRefPubMedGoogle Scholar
  5. 5.
    Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef M (2003) Linezolid versus vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphyloccus aureus nosocomial pneumonia. Chest 2003 (in press)Google Scholar
  6. 6.
    Fagon JY, Chastre J, Hance AJ, Montravers P, Novara A, Gibert C (1993) Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay. Am J Med 94:281–288PubMedGoogle Scholar
  7. 7.
    Fagon J, Patrick H, Haas DW, Torres A, Gibert C, Cheadle WG, Falcone RE, Anholm JD, Paganin F, Fabian TC, Lilienthal F (2000) Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group. Am J Respir Crit Care Med 161:753–762PubMedGoogle Scholar
  8. 8.
    Cruciani M, Gatti G, Lazzarini L, Furlan G, Broccali G, Malena M, Franchini C, Concia E (1996) Penetration of vancomycin into human lung tissue. J Antimicrob Chemother 38:865–869PubMedGoogle Scholar
  9. 9.
    Georges H, Leroy O, Alfandari S, Guery B, Roussel-Delvallez M, Dhennain C, Beaucaire G (1997) Pulmonary deposition of vancomycin in critically ill patients. Eur J Clin Microbial Infect Dis 16:385–388Google Scholar
  10. 10.
    Lamer C, de Beco V, Soler P, Calvat S, Fagon JY, Dombret MC, Farinotti R, Chastre J, Gibert C (1993) Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients. Antimicrob Agents Chemother 37:281–286PubMedGoogle Scholar
  11. 11.
    Conte JE Jr, Golden JA, Kipps J, Zurlinden E (2002) Intrapulmonary pharmacokinetics of linezolid. Antimicrob Agents Chemother 46:1475–1480CrossRefPubMedGoogle Scholar
  12. 12.
    Honeybourne D, Tobin C, Jevons G, Andrews A, Wise R (2002) Intrapulmonary penetration of linezolid. Chest 122 (4 Suppl):159S. AbstractGoogle Scholar
  13. 13.
    Cantu TG, Yamanaka-Yuen NA, Lietman PS (1994) Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis 18:533–543PubMedGoogle Scholar
  14. 14.
    Moise PA, Forrest A, Bhavnani SM, Birmingham MC, Schentag JJ (2000) Area under the inhibitory curve and a pneumonia scoring system for predicting outcomes of vancomycin therapy for respiratory infections by Staphylococcus aureus. Am J Health Syst Pharm 57 [Suppl 2]:S4–S9Google Scholar
  15. 15.
    Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, Thomas F, Timsit JF, Similowski T, Mentec H, Mier L, Dreyfuss D (2001) Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 45:2460–2467CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Marin H. Kollef
    • 1
  • Jordi Rello
    • 2
  • Sue K. Cammarata
    • 3
  • Rodney V. Croos-Dabrera
    • 3
  • Richard G. Wunderink
    • 4
  1. 1.Pulmonary and Critical Care Division, Department of Internal Medicine, School of MedicineWashington UniversitySt. LouisUSA
  2. 2.Critical Care Department, Joan XXIII University HospitalUniversity Rovira I VirgiliTarragonaSpain
  3. 3.PfizerKalamazooUSA
  4. 4.Methodist Healthcare MemphisMemphisUSA

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