Log in | Register

Ventilator-associated pneumonia: present understanding and ongoing debates

Girish B. Nair| Michael S. Niederman
Review
Volume 41, Issue 1 / January , 2015

Pages 34 - 48

Abstract

Introduction

Ventilator-associated pneumonia (VAP) is a common cause of nosocomial infection, and is related to significant utilization of health-care resources. In the past decade, new data have emerged about VAP epidemiology, diagnosis, treatment and prevention.

Results

Classifying VAP strictly based on time since hospitalization (early- and late-onset VAP) can potentially result in undertreatment of drug-resistant organisms in ICUs with a high rate of drug resistance, and overtreatment for patients not infected with resistant pathogens. A combined strategy incorporating diagnostic scoring systems, such as the Clinical Pulmonary Infection Score (CPIS), and either a quantitative or qualitative microbiological specimen, plus serial measurement of biomarkers, leads to responsible antimicrobial stewardship. The newly proposed ventilator-associated events (VAE) surveillance definition, endorsed by the Centers for Disease Control and Prevention, has low sensitivity and specificity for diagnosing VAP and the ability to prevent VAE is uncertain, making it a questionable surrogate for the quality of ICU care. The use of adjunctive aerosolized antibiotic treatment can provide high pulmonary concentrations of the drug and may facilitate shorter durations of therapy for multi-drug-resistant pathogens. A group of preventive strategies grouped as a ‘ventilator bundle’ can decrease VAP rates, but not to zero, and several recent studies show that there are potential barriers to implementation of these prevention strategies.

Conclusion

The morbidity and mortality related to VAP remain high and, in the absence of a gold standard test for diagnosis, suspected VAP patients should be started on antibiotics based on recommendations per the 2005 ATS guidelines and knowledge of local antibiotic susceptibility patterns. Using a combination of clinical severity scores, biomarkers, and cultures might help with reducing the duration of therapy and achieving antibiotic de-escalation.

Keywords

References

  1. Niederman MS, Craven D, Bonten MJ, Chastre J, Craig W, Fagon J, Hall J, Jacoby G, Kollef M, Luna C, Mandell L, Torres A, Wunderink R (2005) Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 171:388–416
    • View reference on publisher's website
  2. Dudeck MA, Horan TC, Peterson KD, Allen-Bridson K, Morrell GC, Pollock DA, Edwards JR (2011) National Healthcare Safety Network (NHSN) report, data summary for 2009, device-associated module. Am J Infect Control 39:349–367
    • View reference on PubMed
    • View reference on publisher's website
  3. Klompas M (2012) Is a ventilator-associated pneumonia rate of zero really possible? Curr Opin Infect Dis 25:176–182
    • View reference on PubMed
    • View reference on publisher's website
  4. Klompas M, Magill S, Robicsek A, Strymish JM, Kleinman K, Evans RS, Lloyd JF, Khan Y, Yokoe DS, Stevenson K, Samore M, Platt R (2012) Objective surveillance definitions for ventilator-associated pneumonia. Crit Care Med 40:3154–3161
    • View reference on PubMed
    • View reference on publisher's website
  5. Heyland D, Cook D, Dodek P, Muscedere J, Day A (2006) A randomized trial of diagnostic techniques for ventilator-associated pneumonia. N Engl J Med 355:2619–2630
    • View reference on publisher's website
  6. Aarts MA, Hancock JN, Heyland D, McLeod RS, Marshall JC (2008) Empiric antibiotic therapy for suspected ventilator-associated pneumonia: a systematic review and meta-analysis of randomized trials. Crit Care Med 36:108–117
    • View reference on PubMed
    • View reference on publisher's website
  7. Kett DH, Cano E, Quartin AA, Mangino JE, Zervos MJ, Peyrani P, Cely CM, Ford KD, Scerpella EG, Ramirez JA (2011) Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study. Lancet Infect Dis 11:181–189
    • View reference on PubMed
    • View reference on publisher's website
  8. Morris AC, Hay AW, Swann DG, Everingham K, McCulloch C, McNulty J, Brooks O, Laurenson IF, Cook B, Walsh TS (2011) Reducing ventilator-associated pneumonia in intensive care: impact of implementing a care bundle. Crit Care Med 39:2218–2224
    • View reference on PubMed
    • View reference on publisher's website
  9. Giantsou E, Liratzopoulos N, Efraimidou E, Panopoulou M, Alepopoulou E, Kartali-Ktenidou S, Minopoulos GI, Zakynthinos S, Manolas KI (2005) Both early-onset and late-onset ventilator-associated pneumonia are caused mainly by potentially multiresistant bacteria. Intensive Care Med 31:1488–1494
  10. Muscedere J, Dodek P, Keenan S, Fowler R, Cook D, Heyland D (2008) Comprehensive evidence-based clinical practice guidelines for ventilator-associated pneumonia: diagnosis and treatment. J Crit Care 23:138–147
    • View reference on PubMed
    • View reference on publisher's website
  11. Gastmeier P, Sohr D, Geffers C, Rüden H, Vonberg RP, Welte T (2009) Early- and late-onset pneumonia: is this still a useful classification? Antimicrob Agents Chemother 53:2714–2718
    • View reference on PubMed
    • View reference on publisher's website
  12. Restrepo M, Peterson J, Fernandez JF, Qin Z, Fisher AC, Nicholson SC (2013) Comparison of the bacterial etiology of early-onset and late-onset ventilator-associated pneumonia in subjects enrolled in 2 large clinical studies. Respir Care 58:1220–1225
    • View reference on PubMed
    • View reference on publisher's website
  13. Ferrer M, Liapikou A, Valencia M, Esperatti M, Theessen A, Antonio Martinez J, Mensa J, Torres A (2010) Validation of the American Thoracic Society-Infectious Diseases Society of America guidelines for hospital-acquired pneumonia in the intensive care unit. Clin Infect Dis 50:945–952
    • View reference on PubMed
    • View reference on publisher's website
  14. Martin-Loeches Deja M, Koulenti D, Dimopoulos G, Marsh B, Torres A, Niederman MS, Rello J (2013) Potentially resistant microorganisms in intubated patients with hospital-acquired pneumonia: the interaction of ecology, shock and risk factors. Intensive Care Med 39:672–681
  15. Iregui M, Ward S, Sherman G, Fraser VJ, Kollef MH (2002) Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 122:262–268
    • View reference on PubMed
    • View reference on publisher's website
  16. Kumar A, Zarychanski R, Light B, Parrillo J, Maki D, Simon D, Laporta D, Lapinsky S, Ellis P, Mirzanejad Y, Martinka G, Keenan S, Wood G, Arabi Y, Feinstein D, Kumar A, Dodek P, Kravetsky L, Doucette S (2010) Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis. Crit Care Med 38:1773–1785
    • View reference on PubMed
    • View reference on publisher's website
  17. Kollef MH (2000) Inadequate antimicrobial treatment: an important determinant of outcome for hospitalized patients. Clin Infect Dis 31(Suppl 4):S131–S138
    • View reference on PubMed
    • View reference on publisher's website
  18. Jones RN (2010) Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis 50:S81–S87
    • View reference on publisher's website
  19. Esperatti M, Ferrer M, Theessen A, Liapikou A, Valencia M, Saucedo LM, Zavala E, Welte T, Torres A (2010) Nosocomial pneumonia in the intensive care unit acquired by mechanically ventilated versus nonventilated patients. Am J Respir Crit Care Med 182:1533–1539
    • View reference on PubMed
    • View reference on publisher's website
  20. Weber DJ, Rutala WA, Sickbert-Bennett EE, Samsa GP, Brown V, Niederman MS (2007) Microbiology of ventilator-associated pneumonia compared with that of hospital-acquired pneumonia. Infect Control Hosp Epidemiol 28:825–831
    • View reference on PubMed
    • View reference on publisher's website
  21. Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332
    • View reference on PubMed
    • View reference on publisher's website
  22. Chastre J, Fagon JY (2002) Ventilator-associated pneumonia. Am J Respir Crit Care Med 165:867–903
    • View reference on PubMed
    • View reference on publisher's website
  23. Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM (1991) Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 143:1121–1129
    • View reference on PubMed
    • View reference on publisher's website
  24. Singh N, Rogers P, Atwood CW, Wagener MM, Yu VL (2000) Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 162:505–511
    • View reference on PubMed
    • View reference on publisher's website
  25. Craven DE, Chroneou A, Zias N, Hjalmarson KI (2009) Ventilator-associated tracheobronchitis: the impact of targeted antibiotic therapy on patient outcomes. Chest 135:521–528
    • View reference on PubMed
    • View reference on publisher's website
  26. Nseir S, Favory R, Jozefowicz E, Decamps F, Dewavrin F, Brunin G, Di Pompeo C, Mathieu D, Durocher A (2008) Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study. Crit Care 12:R62
    • View reference on PubMed
    • View reference on publisher's website
  27. Dallas J, Skrupky L, Abebe N, Boyle WA 3rd, Kollef MH (2011) Ventilator-associated tracheobronchitis in a mixed surgical and medical ICU population. Chest 139:513–518
    • View reference on PubMed
    • View reference on publisher's website
  28. Craven DE, Hjalmarson K (2008) Prophylaxis of ventilator-associated pneumonia: changing culture and strategies to trump disease. Chest 134:898–900
    • View reference on PubMed
    • View reference on publisher's website
  29. Shorr AF, Sherner JH, Jackson WL, Kollef MH (2005) Invasive approaches to the diagnosis of ventilator-associated pneumonia: a meta-analysis. Crit Care Med 33:46–53
    • View reference on PubMed
    • View reference on publisher's website
  30. Berton DC, Kalil AC, Teixeira PJ (2012) Quantitative versus qualitative cultures of respiratory secretions for clinical outcomes in patients with ventilator-associated pneumonia. Cochrane Database Syst Rev 1:CD006482
  31. Zilberberg MD, Shorr AF (2010) Ventilator-associated pneumonia: the clinical pulmonary infection score as a surrogate for diagnostics and outcome. Clin Infect Dis 51:S131–S135
    • View reference on PubMed
    • View reference on publisher's website
  32. Luyt CE, Chastre J, Fagon JY (2004) Value of the clinical pulmonary infection score for the identification and management of ventilator-associated pneumonia. Intensive Care Med 30:844–852
  33. Michel F, Franceschini B, Berger P, Arnal JM, Gainnier M, Sainty JM, Papazian L (2005) Early antibiotic treatment for BAL-confirmed ventilator-associated pneumonia: a role for routine endotracheal aspirate cultures. Chest 127:589–597
    • View reference on PubMed
    • View reference on publisher's website
  34. Luna CM, Blanzaco D, Niederman MS, Matarucco W, Baredes NC, Desmery P, Palizas F, Menga G, Rios F, Apezteguia C (2003) Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med 31:676–682
    • View reference on PubMed
    • View reference on publisher's website
  35. Luyt CE, Guérin V, Combes A, Trouillet JL, Ayed SB, Bernard M, Gibert C, Chastre J (2005) Procalcitonin kinetics as a prognostic marker of ventilator-associated pneumonia. Am J Respir Crit Care Med 171:48–53
    • View reference on PubMed
    • View reference on publisher's website
  36. Ramirez P, Garcia MA, Ferrer M, Aznar J, Valencia M, Sahuquillo JM, Menéndez R, Asenjo MA, Torres A (2008) Sequential measurements of procalcitonin levels in diagnosing ventilator-associated pneumonia. Eur Respir J 31:356–362
    • View reference on PubMed
    • View reference on publisher's website
  37. Klompas M, Kleinman K, Khan Y, Evans RS, Lloyd JF, Stevenson K, Samore M, Platt R (2012) Rapid and reproducible surveillance for ventilator-associated pneumonia. Clin Infect Dis 54:370–377
    • View reference on PubMed
    • View reference on publisher's website
  38. Klompas M, Khan Y, Kleinman K, Evans RS, Lloyd JF, Stevenson K, Samore M, Platt R (2011) Multicenter evaluation of a novel surveillance paradigm for complications of mechanical ventilation. PLoS One 6:e18062
    • View reference on PubMed
    • View reference on publisher's website
  39. Magill SS, Klompas M, Balk R, Burns SM, Deutschman CS, Diekema D, Fridkin S, Greene L, Guh A, Gutterman D, Hammer B, Henderson D, Hess DR, Hill NS, Horan T, Kollef M, Levy M, Septimus E, Vanantwerpen C, Wright D, Lipsett P (2013) Executive summary: developing a new, national approach to surveillance for ventilator-associated events. Ann Am Thorac Soc 10:S220–S223
    • View reference on PubMed
    • View reference on publisher's website
  40. Hayashi Y, Morisawa K, Klompas M, Jones M, Bandeshe H, Boots R, Lipman J, Paterson DL (2013) Toward improved surveillance: the impact of ventilator-associated complications on length of stay and antibiotic use in patients in intensive care units. Clin Infect Dis 56:471–477
    • View reference on PubMed
    • View reference on publisher's website
  41. Muscedere J, Sinuff T, Heyland DK, Dodek PM, Keenan SP, Wood G, Jiang X, Day AG, Laporta D, Klompas M (2013) The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilated. Chest 144:1453–1460
    • View reference on PubMed
    • View reference on publisher's website
  42. Klein Klouwenberg PM, van Mourik MS, Ong DS, Horn J, Schultz MJ, Cremer OL, Bonten MJ (2014) Electronic implementation of a novel surveillance paradigm for ventilator-associated events: feasibility and validation. Am J Respir Crit Care Med 189:947–955
    • View reference on PubMed
    • View reference on publisher's website
  43. Kollef MH (2001) Hospital-acquired pneumonia and de-escalation of antimicrobial treatment. Crit Care Med 29:1473–1475
    • View reference on PubMed
    • View reference on publisher's website
  44. Heyland DK, Dodek P, Muscedere J, Day A, Cook D (2008) Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 36:737–744
    • View reference on PubMed
    • View reference on publisher's website
  45. Wilke M, Grube RF, Bodmann KF (2011) Guideline-adherent initial intravenous antibiotic therapy for hospital-acquired/ventilator-associated pneumonia is clinically superior, saves lives and is cheaper than non guideline adherent therapy. Eur J Med Res 16:315–323
    • View reference on PubMed
    • View reference on publisher's website
  46. Piskin N, Aydemir H, Oztoprak N, Akduman D, Comert F, Kokturk F, Celebi G (2012) Inadequate treatment of ventilator-associated and hospital-acquired pneumonia: risk factors and impact on outcomes. BMC Infect Dis 12:268
    • View reference on PubMed
    • View reference on publisher's website
  47. Tumbarello M, De Pascale G, Trecarichi EM, Spanu T, Antonicelli F, Maviglia R, Pennisi MA, Bello G, Antonelli M (2013) Clinical outcomes of Pseudomonas aeruginosa pneumonia in intensive care unit patients. Intensive Care Med 39:682–692
  48. Trouillet JL, Vuagnat A, Combes A, Kassis N, Chastre J, Gibert C (2002) Pseudomonas aeruginosa ventilator-associated pneumonia: comparison of episodes due to piperacillin-resistant versus piperacillin-susceptible organisms. Clin Infect Dis 34:1047–1054
    • View reference on PubMed
    • View reference on publisher's website
  49. Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, Huskins WC, Paterson DL, Fishman NO, Carpenter CF, Brennan PJ, Billeter M, Hooton TM (2007) Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 44:159–177
    • View reference on PubMed
    • View reference on publisher's website
  50. Niederman MS, Soulountsi V (2011) De-escalation therapy: is it valuable for the management of ventilator-associated pneumonia? Clin Chest Med 32:517–534
    • View reference on PubMed
    • View reference on publisher's website
  51. Joung MK, Lee JA, Moon SY, Cheong HS, Joo EJ, Ha YE, Sohn KM, Chung SM, Suh GY, Chung DR, Song JH, Peck KR (2011) Impact of de-escalation therapy on clinical outcomes for intensive care unit-acquired pneumonia. Crit Care 15:R79
    • View reference on PubMed
    • View reference on publisher's website
  52. Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A, Corcia-Palomo Y, Fernández-Delgado E, Herrera-Melero I, Ortiz-Leyba C, Márquez-Vácaro JA (2014) De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med 40:32–40
  53. Raman K, Nailor MD, Nicolau DP, Aslanzadeh J, Nadeau M, Kuti JL (2013) Early antibiotic discontinuation in patients with clinically suspected ventilator-associated pneumonia and negative quantitative bronchoscopy cultures. Crit Care Med 41:1656–1663
    • View reference on PubMed
    • View reference on publisher's website
  54. Luna CM, Sarquis S, Niederman MS, Sosa FA, Otaola M, Bailleau N, Vay CA, Famiglietti A, Irrazabal C, Capdevila AA (2013) Is a strategy based on routine endotracheal cultures the best way to prescribe antibiotics in ventilator-associated pneumonia? Chest 144:63–71
    • View reference on PubMed
    • View reference on publisher's website
  55. Brusselaers N, Labeau S, Vogelaers D, Blot S (2013) Value of lower respiratory tract surveillance cultures to predict bacterial pathogens in ventilator-associated pneumonia: systematic review and diagnostic test accuracy meta-analysis. Intensive Care Med 39:365–375
  56. Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, Schortgen F, Lasocki S, Veber B, Dehoux M, Bernard M, Pasquet B, Régnier B, Brun-Buisson C, Chastre J, Wolff M (2010) Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet 375:463–474
    • View reference on PubMed
    • View reference on publisher's website
  57. Stolz D, Smyrnios N, Eggimann P, Pargger H, Thakkar N, Siegemund M, Marsch S, Azzola A, Rakic J, Mueller B, Tamm M (2009) Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study. Eur Respir J 34:1364–1375
    • View reference on PubMed
    • View reference on publisher's website
  58. Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S (2003) Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 290:2588–2598
    • View reference on PubMed
    • View reference on publisher's website
  59. Capellier G, Mockly H, Charpentier C, Annane D, Blasco G, Desmettre T, Roch A, Faisy C, Cousson J, Limat S, Mercier M, Papazian L (2012) Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One 7:e41290
    • View reference on PubMed
    • View reference on publisher's website
  60. Kollef MH, Chastre J, Clavel M, Restrepo MI, Michiels B, Kaniga K, Cirillo I, Kimko H, Redman R (2012) A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Crit Care 16:R218
    • View reference on PubMed
    • View reference on publisher's website
  61. Dimopoulos G, Poulakou G, Pneumatikos IA, Armaganidis A, Kollef MH, Matthaiou DK (2013) Short- vs long-duration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis. Chest 144:1759–1767
    • View reference on PubMed
    • View reference on publisher's website
  62. Walkey AJ, O’Donnell MR, Wiener RS (2011) Linezolid vs glycopeptide antibiotics for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a meta-analysis of randomized controlled trials. Chest 139:1148–1155
    • View reference on PubMed
    • View reference on publisher's website
  63. Kalil AC, Murthy MH, Hermsen ED, Neto FK, Sun J, Rupp ME (2010) Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: a systematic review and meta-analysis. Crit Care Med 38:1802–1808
    • View reference on PubMed
    • View reference on publisher's website
  64. Wunderink RG, Niederman MS, Kollef MH, Shorr AF, Kunkel MJ, Baruch A, McGee WT, Reisman A, Chastre J (2012) Linezolid in methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a randomized, controlled study. Clin Infect Dis 54:621–629
    • View reference on PubMed
    • View reference on publisher's website
  65. Kalil AC, Klompas M, Haynatzki G, Rupp ME (2013) Treatment of hospital-acquired pneumonia with linezolid or vancomycin: a systematic review and meta-analysis. BMJ Open 3:e003912
    • View reference on PubMed
    • View reference on publisher's website
  66. Wunderink RG, Shorr AF, Niederman MS, Kollef MH, McGee WT, Chastre J (2014) Which antibiotic for hospital acquired pneumonia caused by MRSA? http://www.bmj.com/content/348/bmj.g1469/rr/689916. Accessed 6 Apr 14
  67. Jiang H, Tang RN, Wang J (2013) Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: meta-analysis of randomised controlled trials. Eur J Clin Microbiol Infect Dis 32:1121–1128
    • View reference on PubMed
    • View reference on publisher's website
  68. Peyrani P, Wiemken TL, Kelley R, Zervos MJ, Kett DH, File TM Jr, Stein GE, Ford KD, Scerpella EG, Welch V, Ramirez JA (2014) Higher clinical success in patients with ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus treated with linezolid compared with vancomycin: results from the IMPACT-HAP study. Crit Care 18:R118
    • View reference on PubMed
    • View reference on publisher's website
  69. Freire AT, Melnyk V, Kim MJ, Datsenko O, Dzyublik O, Glumcher F, Chuang YC, Maroko RT, Dukart G, Cooper CA, Korth-Bradley JM, Dartois N, Gandjini H (2010) Comparison of tigecycline with imipenem/cilastatin for the treatment of hospital-acquired pneumonia. Diagn Microbiol Infect Dis 68:140–151
    • View reference on PubMed
    • View reference on publisher's website
  70. Guner R, Hasanoglu I, Keske S, Kalem AK, Tasyaran MA (2011) Outcomes in patients infected with carbapenem-resistant Acinetobacter baumannii and treated with tigecycline alone or in combination therapy. Infection 39:515–518
    • View reference on PubMed
    • View reference on publisher's website
  71. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC (2013) Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother 57:1756–1762
    • View reference on PubMed
    • View reference on publisher's website
  72. Montravers P, Dupont H, Bedos JP, Bret P (2014) Tigecycline use in critically ill patients: a multicentre prospective observational study in the intensive care setting. Intensive Care Med 40:988–997
  73. Niederman MS, Chastre J, Corkery K, Fink JB, Luyt CE, García MS (2012) BAY41-6551 achieves bactericidal tracheal aspirate amikacin concentrations in mechanically ventilated patients with Gram-negative pneumonia. Intensive Care Med 38:263–271
  74. Lu Q, Yang J, Liu Z, Gutierrez C, Aymard G, Rouby JJ (2011) Nebulized ceftazidime and amikacin in ventilator-associated pneumonia caused by Pseudomonas aeruginosa. Am J Respir Crit Care Med 184:106–115
    • View reference on PubMed
    • View reference on publisher's website
  75. Nicasio AM, Eagye KJ, Nicolau DP, Shore E, Palter M, Pepe J (2010) Pharmacodynamic-based clinical pathway for empiric antibiotic choice in patients with ventilator-associated pneumonia. J Crit Care 25:69–77
    • View reference on PubMed
    • View reference on publisher's website
  76. Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C, Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL (2013) Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Disease 56:236–244
    • View reference on publisher's website
  77. Croce MA, Brasel KJ, Coimbra R, Adams CA Jr, Miller PR, Pasquale MD, McDonald CS, Vuthipadadon S, Fabian TC, Tolley EA (2013) National Trauma Institute prospective evaluation of the ventilator bundle in trauma patients: does it really work? J Trauma Acute Care Surg 74:354–360
  78. Chaari A, Kssibi H, Zribi W, Medhioub F, Chelly H, Algia NB, Hamida CB, Bahloul M, Bouaziz M (2013) Ventilator-associated pneumonia in trauma patients with open tracheotomy: predictive factors and prognosis impact. J Emerg Trauma Shock 6:246–251
    • View reference on PubMed
    • View reference on publisher's website
  79. Parks NA, Magnotti LJ, Weinberg JA, Zarzaur BL, Schroeppel TJ, Swanson JM, Fabian TC, Croce MA (2012) Use of the clinical pulmonary infection score to guide therapy for ventilator-associated pneumonia risks antibiotic overexposure in patients with trauma. J Trauma Acute Care Surg 73:52–58
    • View reference on PubMed
    • View reference on publisher's website
  80. Schmelzer TM, Christmas AB, Norton HJ, Heniford BT, Sing RF (2013) Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients. Am Surg 79:1185–1190
    • View reference on PubMed
  81. Bouadma L, Wolff M, Lucet JC (2012) Ventilator-associated pneumonia and its prevention. Curr Opin Infect Dis 25:395–404
    • View reference on PubMed
    • View reference on publisher's website
  82. Resar R, Pronovost P, Haraden C, Simmonds T, Rainey T, Nolan T (2005) Using a bundle approach to improve ventilator care processes and reduce ventilator-associated pneumonia. Jt Comm J Qual Patient Saf 31:243–248
    • View reference on PubMed
  83. Sinuff T, Muscedere J, Cook DJ, Dodek PM, Anderson W, Keenan SP, Wood G, Tan R, Haupt MT, Miletin M, Bouali R, Jiang X, Day AG, Overvelde J, Heyland DK (2013) Implementation of clinical practice guidelines for ventilator-associated pneumonia: a multicenter prospective study. Crit Care Med 41:15–23
    • View reference on PubMed
    • View reference on publisher's website
  84. Griffiths J, Barber VS, Morgan L, Young JD (2005) Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation. BMJ 330:1243
    • View reference on PubMed
    • View reference on publisher's website
  85. Blot F, Similowski T, Trouillet JL, Chardon P, Korach JM, Costa MA, Journois D, Thiéry G, Fartoukh M, Pipien I, Bruder N, Orlikowski D, Tankere F, Durand-Zaleski I, Auboyer C, Nitenberg G, Holzapfel L, Tenaillon A, Chastre J, Laplanche A (2008) Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients. Intensive Care Med 34:1779–1787
  86. Terragni PP, Antonelli M, Fumagalli R, Faggiano C, Berardino M, Pallavicini FB, Miletto A, Mangione S, Sinardi AU, Pastorelli M, Vivaldi N, Pasetto A, Della Rocca G, Urbino R, Filippini C, Pagano E, Evangelista A, Ciccone G, Mascia L, Ranieri VM (2010) Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients: a randomized controlled trial. JAMA 303:1483–1489
    • View reference on PubMed
    • View reference on publisher's website
  87. Young D, Harrison DA, Cuthbertson BH, Rowan K (2013) Effect of early vs late tracheostomy placement on survival in patients receiving mechanical ventilation: the TracMan randomized trial. JAMA 309:2121–2129
    • View reference on PubMed
    • View reference on publisher's website

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement