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Attributable mortality of ventilator-associated pneumonia: respective impact of main characteristics at ICU admission and VAP onset using conditional logistic regression and multi-state models

Molière Nguile-Makao| Jean-Ralph Zahar| Adrien Français| Alexis Tabah| Maité Garrouste-Orgeas| Bernard Allaouchiche| Dany Goldgran-Toledano| Elie Azoulay| Christophe Adrie| Samir Jamali| Christophe Clec’h| Bertrand Souweine| Jean-Francois Timsit
Original
Volume 36, Issue 5 / May , 2010

Pages 781 - 789

Abstract

Purpose

Methods for estimating the excess mortality attributable to ventilator-associated pneumonia (VAP) should handle VAP as a time-dependent covariate, since the probability of experiencing VAP increases with the time on mechanical ventilation. VAP-attributable mortality (VAP-AM) varies with definitions, case-mix, causative microorganisms, and treatment adequacy. Our objectives here were to compare VAP-AM estimates obtained using a traditional cohort analysis, a multistate progressive disability model, and a matched-cohort analysis; and to compare VAP-AM estimates according to VAP characteristics.

Methods

We used data from 2,873 mechanically ventilated patients in the Outcomerea® database. Among these patients from 12 intensive care units, 434 (15.1%) experienced VAP; of the remaining patients, 1,969 (68.5%) were discharged alive and 470 (16.4%) died. With the multistate model, VAP-AM was 8.1% (95% confidence interval [95%CI], 3.1–13.1%) for 120 days’ complete observation, compared to 10.4% (5.6–24.5%) using a matched-cohort approach (2,769 patients) with matching on mechanical ventilation duration followed by conditional logistic regression. VAP-AM was higher in surgical patients and patients with intermediate (but not high) Simplified Acute Physiologic Score II values at ICU admission. VAP-AM was significantly influenced by time to VAP but not by resistance of causative microorganisms. Higher Logistic Organ Dysfunction score at VAP onset dramatically increased VAP-AM (to 31.9% in patients with scores above 7).

Conclusion

A multistate model that appropriately handled VAP as a time-dependent event produced lower VAP-AM values than conditional logistic regression. VAP-AM varied widely with case-mix. Disease severity at VAP onset markedly influenced VAP-AM; this may contribute to the variability of previous estimates.

Keywords

References

  1. Klompas M, Platt R (2007) Ventilator-associated pneumonia—the wrong quality measure for benchmarking. Ann Intern Med 147:803–805
    • View reference on PubMed
  2. Safdar N, Dezfulian C, Collard HR, Saint S (2005) Clinical and economic consequences of ventilator-associated pneumonia: a systematic review. Crit Care Med 33:2184–2193
    • View reference on publisher's website
    • View reference on PubMed
  3. Melsen WG, Rovers MM, Bonten MJ (2009) Ventilator-associated pneumonia and mortality: a systematic review of observational studies. Crit Care Med 37:2709–2718
    • View reference on publisher's website
    • View reference on PubMed
  4. Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903
    • View reference on PubMed
  5. Klompas M (2007) Does this patient have ventilator-associated pneumonia? Jama 297:1583–1593
    • View reference on publisher's website
    • View reference on PubMed
  6. Valles J, Pobo A, Garcia-Esquirol O, Mariscal D, Real J, Fernandez R (2007) Excess ICU mortality attributable to ventilator-associated pneumonia: the role of early vs late onset. Intensive Care Med 33:1363–1368
  7. Timsit JF (2007) Bronchoalveolar lavage for VAP diagnosis: patients must be sampled before any change of antimicrobial therapy. Intensive Care Med 33:1690–1693
  8. Baker AM, Meredith JW, Haponik EF (1996) Pneumonia in intubated trauma patients Microbiology and outcomes. Am J Respir Crit Care Med 153:343–349
    • View reference on PubMed
  9. Markowicz P, Wolff M, Djedaini K, Cohen Y, Chastre J, Delclaux C, Merrer J, Herman B, Veber B, Fontaine A, Dreyfuss D (2000) Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome. Incidence, prognosis, and risk factors. ARDS Study Group. Am J Respir Crit Care Med 161:1942–1948
    • View reference on PubMed
  10. Nseir S, Di Pompeo C, Soubrier S, Cavestri B, Jozefowicz E, Saulnier F, Durocher A (2005) Impact of ventilator-associated pneumonia on outcome in patients with COPD. Chest 128:1650–1656
    • View reference on publisher's website
    • View reference on PubMed
  11. Delclaux C, Roupie E, Blot F, Brochard L, Lemaire F, Brun-Buisson C (1997) Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: incidence and diagnosis. Am J Respir Crit Care Med 156:1092–1098
    • View reference on PubMed
  12. Clec’h C, Timsit JF, De Lassence A, Azoulay E, Alberti C, Garrouste-Orgeas M, Mourvilier B, Troche G, Tafflet M, Tuil O, Cohen Y (2004) Efficacy of adequate early antibiotic therapy in ventilator-associated pneumonia: influence of disease severity. Intensive Care Med 30:1327–1333
  13. Moine P, Timsit JF, De Lassence A, Troche G, Fosse JP, Alberti C, Cohen Y (2002) Mortality associated with late-onset pneumonia in the intensive care unit: results of a multi-center cohort study. Intensive Care Med 28:154–163
  14. Barlow WE, Ichikawa L, Rosner D, Izumi S (1999) Analysis of case-cohort designs. J Clin Epidemiol 52:1165–1172
    • View reference on publisher's website
    • View reference on PubMed
  15. Wolkewitz M, Beyersmann J, Gastmeier P, Schumacher M (2009) Modeling the effect of time-dependent exposure on intensive care unit mortality. Intensive Care Med 35:826–832
  16. Beyersmann J, Gastmeier P, Grundmann H, Barwolff S, Geffers C, Behnke M, Ruden H, Schumacher M (2006) Use of multistate models to assess prolongation of intensive care unit stay due to nosocomial infection. Infect Control Hosp Epidemiol 27:493–499
    • View reference on publisher's website
    • View reference on PubMed
  17. Schumacher M, Wangler M, Wolkewitz M, Beyersmann J (2007) Attributable mortality due to nosocomial infections: a simple and useful application of multistate models. Methods Inf Med 46:595–600
    • View reference on PubMed
  18. Zahar JR, Nguile-Makao M, Français A, Schwebel C, Garrouste-Orgeas M, Goldgran-Toledano D, Azoulay E, Thuong M, Jamali S, Cohen Y et al (2009) Predicting the risk of documented ventilator-associated pneumonia for benchmarking: construction and validation of a score. Crit Care Med 37:2545–2551
    • View reference on publisher's website
    • View reference on PubMed
  19. Wangler M, Beyersmann J, Schumacher M (2006) changeLOS: an R-package for change in length of hospital stay based on the Aalen-Johansen estimator. R Newsl 6(2):31–35
  20. Wolkewitz M, Vonberg R, Grundmann H, Beyersmann J, Gastmeier P, Bärwolff S, Geffers C, Behnke M, Rüden H, Schumacher M (2008) Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. Critical Care 12:R44–R44
    • View reference on publisher's website
    • View reference on PubMed
  21. Beyersmann J, Wolkewitz M, Schumacher M (2008) The impact of time-dependent bias in proportional hazards modelling. Stat Med 27:6439–6454
    • View reference on publisher's website
    • View reference on PubMed
  22. Andersen PK, Keiding N (2002) Multi-state models for event history analysis. Stat Methods Med Res 11:91–115
    • View reference on publisher's website
    • View reference on PubMed
  23. Chevret S (2001) Logistic or Cox model to identify risk factors of nosocomial infection: still a controversial issue. Intensive Care Med 27:1559–1560
  24. Schoenfeld D (2006) Survival methods, including those using competing risk analysis, are not appropriate for intensive care unit outcome studies. Crit Care 10:103
    • View reference on publisher's website
    • View reference on PubMed
  25. Bueno-Cavanillas A, Delgado-Rodriguez M, Lopez-Luque A, Schaffino-Cano S, Galvez-Vargas R (1994) Influence of nosocomial infection on mortality rate in an intensive care unit. Crit Care Med 22:55–60
    • View reference on PubMed
  26. Kim PW, Perl TM, Keelaghan EF, Langenberg P, Perencevich EN, Harris AD, Song X, Roghmann MC (2005) Risk of mortality with a bloodstream infection is higher in the less severely ill at admission. Am J Respir Crit Care Med 171:616–620
    • View reference on publisher's website
    • View reference on PubMed
  27. Heyland DK, Cook DJ, Griffith L, Keenan SP, Brun-Buisson C (1999) The attributable morbidity and mortality of ventilator-associated pneumonia in the critically ill patient. The Canadian Critical Trials Group. Am J Respir Crit Care Med 159:1249–1256
    • View reference on PubMed
  28. Ibrahim EH, Ward S, Sherman G, Kollef MH (2000) A comparative analysis of patients with early-onset vs late-onset nosocomial pneumonia in the ICU setting. Chest 117:1434–1442
    • View reference on publisher's website
    • View reference on PubMed
  29. Kollef MH, Silver P, Murphy DM, Trovillion E (1995) The effect of late-onset ventilator-associated pneumonia in determining patient mortality. Chest 108:1655–1662
    • View reference on publisher's website
    • View reference on PubMed
  30. Timsit JF, Fosse JP, Troche G, de Lassence A, Alberti C, Garrouste-Orgeat M, Bornstain C, Adrie C, Cheval C, Chevret S (2002) Calibration and discrimination of daily LOD score in predicting hospital mortality of critically ill patients, comparison with daily SOFA score. Crit Care Med 30:2003–2013
  31. Combes A, Luyt CE, Fagon JY, Wollf M, Trouillet JL, Gibert C, Chastre J (2004) Impact of methicillin resistance on outcome of Staphylococcus aureus ventilator-associated pneumonia. Am J Respir Crit Care Med 170:786–792
    • View reference on publisher's website
    • View reference on PubMed
  32. Zahar JR, Clec’h C, Tafflet M, Garrouste-Orgeas M, Jamali S, Mourvillier B, De Lassence A, Descorps-Declere A, Adrie C, Costa de Beauregard MA, Azoulay E, Schwebel C, Timsit JF (2005) Is methicillin resistance associated with a worse prognosis in Staphylococcus aureus ventilator-associated pneumonia? Clin Infect Dis 41:1224–1231
    • View reference on publisher's website
    • View reference on PubMed
  33. Linares JF, Lopez JA, Camafeita E, Albar JP, Rojo F, Martinez JL (2005) Overexpression of the multidrug efflux pumps MexCD-OprJ and MexEF-OprN is associated with a reduction of type III secretion in Pseudomonas aeruginosa. J Bacteriol 187:1384–1391
    • View reference on publisher's website
    • View reference on PubMed
  34. Crouch Brewer S, Wunderink RG, Jones CB, Leeper KV Jr (1996) Ventilator-associated pneumonia due to Pseudomonas aeruginosa. Chest 109:1019–1029
    • View reference on publisher's website
    • View reference on PubMed
  35. Lisboa T, Diaz E, Sa-Borges M, Socias A, Sole-Violan J, Rodriguez A, Rello J (2008) The ventilator-associated pneumonia PIRO score: a tool for predicting ICU mortality and health-care resources use in ventilator-associated pneumonia. Chest 134:1208–1216
    • View reference on publisher's website
    • View reference on PubMed
  36. Uckay I, Ahmed QA, Sax H, Pittet D (2008) Ventilator-associated pneumonia as a quality indicator for patient safety? Clin Infect Dis 46:557–563
    • View reference on publisher's website
    • View reference on PubMed

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