Download PDF
Semin Respir Crit Care Med 2002; 23(5): 427-434
DOI: 10.1055/s-2002-35713
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

The Pathogenesis of Ventilator-Associated Pneumonia

Mark J. Rumbak
  • Division of Pulmonary, Critical Care, and Occupational Medicine, College of Medicine, University of South Florida, Tampa, Florida
Further Information

Publication History

Publication Date:
25 November 2002 (online)

    Permissions and Reprints

ABSTRACT

Of the four routes of infection pathogenic bacteria can take, the inhalation and aspiration ones are the most important. Inhalation pneumonia is usually due to manipulation of the ventilator tubing and aspiration of the infected condensate. Aspiration of the colonized oropharyngeal contents through the open vocal cords and eventually around the blown up endotracheal cuff allows bacteria to invade the trachea and main bronchi. Reflux of the bacteria and infection of the biofilm on the inner surface of the endotracheal tube is the source for recurrent seeding of pathogenic bacteria into the lungs, causing ventilator-associated pneumonia.

KEYWORDS

Ventilator-associated pneumonia - etiology - pathogenesis - aspiration - inhalation

REFERENCES

  • 1 Haley R W, Hooten T M, Culver D H. Nosocomial infections in US hospitals, 1975-1976; estimated frequency by selected characteristics of patients.  Am J Med . 1981;  70 947-959
    PubMedGoogle Scholar
  • 2 Centers for Disease Control and Prevention. Monitoring hospital-acquired infections to promote patient safety: United States, 1990-1999.  MMWR . 2000;  49 149-153
    PubMedGoogle Scholar
  • 3 Bell R C, Coalson J J, Smith J D, Johanson W G. Multiple organ system failure and infection in ARDS.  Ann Intern Med . 1983;  99 293-298
    PubMedGoogle Scholar
  • 4 Meduri G U. Ventilator-associated pneumonia in patients with respiratory failure.  Chest . 1990;  97 1208-1218
    PubMedGoogle Scholar
  • 5 Rumbak M J. Ventilator-associated pneumonia.  J Respir Dis . 2000;  21 321-327
    PubMedGoogle Scholar
  • 6 Green G M, Jukab G J, Low R B. Defence mechanisms of the respiratory membrane.  Am Rev Respir Dis . 1997;  155
    PubMedGoogle Scholar
  • 7 Huxley E J, Viroslav F, Gray W R. Pharyngeal aspiration in normal adults and patients with depressed level of consciousness.  Am J Med . 1978;  307
    CrossrefPubMedGoogle Scholar
  • 8 Kunkel S L, Streiter R M. Cytokine networking in lung inflammation.  Hosp Pract . 1990;  153 63-69
    PubMedGoogle Scholar
  • 9 Dail D H, Hammer S P. Bacterial Infection, Pulmonary Pathology.  New York: Springer 1994: 155-330
    Google Scholar
  • 10 Fabragas N, Torres A, El Ebiary M. Histopathologic and microbiologic aspects of ventilator-associated pneumonia.  Anesth . 1984;  4 760-771
    PubMedGoogle Scholar
  • 11 Fabregas N, Ewig S, Torres A. The clinical diagnosis of ventilator-associated pneumonia revisited: comparative validation using immediate post-mortem lung biopsies.  Thorax . 1999;  54 10
    PubMedGoogle Scholar
  • 12 Craven D E, Goularte T A, Make B J. Contaminated condensate in mechanical-ventilator circuits: a risk factor for nosocomial pneumonia?.  Am Rev Respir Dis . 1984;  129 625-628
    PubMedGoogle Scholar
  • 13 Daschner F, Kappenstein L, Schuster F. Influence of disposal (``Conchapak'') and reusable humidifying systems on the incidence of ventilation pneumonia.  J Hosp Infect . 1988;  11 161-168
    PubMedGoogle Scholar
  • 14 Rhame F S, Streifel S T, McComb C. Bubbling humidifier produces microaerosols, which can carry bacteria.  Infect Control . 1986;  7 403-407
    PubMedGoogle Scholar
  • 15 Craven D E, Connolly Jr G M, Lichenberg D A, et al Contamination of mechanical ventilators with tubing changes every 24 or 48 hours. N Engl J Med .  1982;  306 1505-1509
    PubMedGoogle Scholar
  • 16 Dreyfuss D, Djedaini K, Weber P. Prospective study of nosocomial pneumonia and of patients and circuit colonization during mechanical ventilation with circuit changes every 48 hours versus no change.  Am Rev Respir Dis . 1991;  143 738-743
    PubMedGoogle Scholar
  • 17 Kollef M H, Shapiro S D, Fraser V J. Mechanical ventilation with or without 7-day circuit changes: a randomized controlled trial.  Ann Intern Med . 1995;  123 168-174
    PubMedGoogle Scholar
  • 18 Stamm A M. Ventilator-associated pneumonia and frequency of circuit changes.  Am J Infect Control . 1998;  26 71-73
    PubMedGoogle Scholar
  • 19 Dreyfus D, Djedaini K, Gros I. Mechanical ventilation with heated humidifiers, or heat and moisture exchangers: effects on patient colonization and incidence of nosocomial pneumonia.  Am J Respir Crit Care Med . 1995;  151 986-992
    PubMedGoogle Scholar
  • 20 Kirton O C, DeHaven B, Morgan J. A prospective, randomized comparison of an in-line heat moisture exchange filter and heated wire humidifies: rates of ventilator-associated early-onset (community-acquired) or late-onset (hospital-acquired) pneumonia and incidence of endotracheal tube occlusion.  Chest . 1997;  112 1055-1059
    PubMedGoogle Scholar
  • 21 Boisson C, Viviand X, Arnaund X. Changing a hydrophobic heat and moisture exchanger after 48 hours rather than 24 hours: a clinical and microbiological evaluation.  Intens Care Med . 1999;  25 1237-1243
    PubMedGoogle Scholar
  • 22 Cobley M, Atkins M, Jones P L. Environmental contamination during tracheal suction: a comparison of disposable conventional catheters with a multiple-use closed system device.  Anesthesia . 1991;  46 957-961
    PubMedGoogle Scholar
  • 23 Kollef M H, Prentice D, Shapiro S D. Mechanical ventilation with or without daily changes of in-line suction catheters.  Am J Respir Crit Care Med . 1997;  156 466-472
    PubMedGoogle Scholar
  • 24 Macrae W, Wallace P. Aspiration around high-volume, low-pressure endotracheal cuff.  Brit Med J Clin Res Ed . 1981;  283 1220
    PubMedGoogle Scholar
  • 25 Feldman C, Kassel M, Cantrell J. The presence and sequence of endotracheal tube colonization in patients undergoing mechanical ventilation.  Eur Respir J . 1999;  13 546-551
    CrossrefPubMedGoogle Scholar
  • 26 Marquette C H, Copin M C, Wallet F. Diagnostic tests for pneumonia in ventilated patients: prospective evaluation of diagnostic accuracy using histology as a diagnostic gold standard.  Am J Respir and Crit Care Med . 1995;  151 1878-1888
    CrossrefPubMedGoogle Scholar
  • 27 Rumbak M J, Newton M, Truncale T. A prospective, randomized study comparing early percutaneous dilatational tracheotomy to prolonged translaryngeal intubation in critically ill medical patients (in press).  N Engl J Med.
    PubMedGoogle Scholar
  • 28 Torres A, Aznar R, Gatell J R. Incidence, risk factors and prognostic factors of nosocomial pneumonia in mechanical ventilated patients.  Am Rev Respir Dis . 1990;  142 523-528
    CrossrefPubMedGoogle Scholar
  • 29 Vallês J, Artigas A, Rello J. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia.  Ann Intern Med . 1995;  122 179-186
    PubMedGoogle Scholar
  • 30 Kollef M H, Skubas N J, Sundt T M. A randomized clinical trial or continuous aspiration of subglottic secretions in cardiac surgical patients Chest .  1999;  116 1339-1346
    PubMedGoogle Scholar
  • 31 Niederman M S. Pathogenesis of airway colonization: lessons learned from studies of bacterial adherence.  Eur Resp J . 1994;  7 1737-1740
    PubMedGoogle Scholar
  • 32 Johanson W G, Pierce A K, Sanford J P. Changing pharyngeal bacterial flora of hospitalized patients.  N Engl J Med . 1969;  281 1137-1140
    CrossrefPubMedGoogle Scholar
  • 33 Ewig S, Torres A, El-Ebiary M. Bacterial colonization patterns in mechanically ventilated patients with traumatic head injury.  Am J Respir Crit Care Med . 1999;  159 188-198
    CrossrefPubMedGoogle Scholar
  • 34 Delclaux C, Roupie E, Blot F. Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome.  Am J Respir Crit Care Med . 1997;  156 1092-1098
    PubMedGoogle Scholar
  • 35 Sirvent J M, Torres A, Vidaur L. Tracheal colonization within 24 hours of intubated patients with head trauma: risk factor for developing early-onset ventilator-associated pneumonia.  Intens Care Med . 2000;  26 1369-1372
    PubMedGoogle Scholar
  • 36 Torres A, Aznar R, Gatell J M. Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients.  Am Rev Respir Dis . 1990;  142 523-528
    CrossrefPubMedGoogle Scholar
  • 37 Johanson Jr G W, Pierce A K, Sanford J P, Thomas G D. Nosocomial respiratory infections with gram negative bacilli: the significance of colonization of the respiratory tract.  Ann Intern Med . 1992;  77 701-706
    PubMedGoogle Scholar
  • 38 Bonten M J, Gaillard C A, van der Geest S. The role of intragastric acidity and stress ulcer prophylaxis on colonization and infection in mechanically ventilated patients: a stratified, randomized, double blind study of sucralfate versus antacids.  Am J Respir Crit Care Med . 1997;  152 1825-1834
    PubMedGoogle Scholar
  • 39 Delclaux C, Roupie E, Blot F. Lower respiratory tract colonization and infection during severe acute respiratory distress syndrome: incidence and diagnosis.  Am J Respir Crit Care Med . 1997;  156 1092-1098
    PubMedGoogle Scholar
  • 40 Niederman M S, Mantovani R, Schoch P. Patterns and routes of tracheobronchial colonization in mechanically ventilated patients.  Chest . 1989;  95 155-161
    PubMedGoogle Scholar
  • 41 Rumbak M J, Bass R. Sputum correlates with protected specimen brush in long term ventilated who have clinical pneumonia.  Chest . 1994;  106 531-534
    PubMedGoogle Scholar
  • 42 Pittet D, Eggimann P, Rubinovitch B. Prevention of ventilator-associated pneumonia by oral decontamination: just another SDD study?.  Am J Respir Crit Care Med . 2001;  164 338-339
    PubMedGoogle Scholar
  • 43 Bergmans D C, Bonten M J, Gaillard C A. Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.  Am J Respir Crit Care Med . 2001;  164 382-388
    PubMedGoogle Scholar
  • 44 Estes R J, Meduri G U. The pathogenesis of ventilator-associated pneumonia, I: Mechanism of bacterial transcolonization and airway inoculation.  Intens Care Med . 1995;  21 365-383
    PubMedGoogle Scholar
  • 45 Scannapieco F A, Stewart E M, Mylotte J M. Colonization of dental plaque by respiratory pathogens in medical intensive care unit.  Crit Care Med . 1992;  20 740-745
    CrossrefPubMedGoogle Scholar
  • 46 Rumbak M J, Cancio M. Significant reduction in methicillin-resistant Staphylococcus aureus ventilator-associated pneumonia following institution of a prevention protocol.  Crit Care Med . 1995;  23 1200-1203
    PubMedGoogle Scholar
  • 47 Kimura A, Mochizuki T, Nishizawa K. Trimethoprim-sulfamethoxazole for the prevention of methicillin resistant Staphylococcus aureus pneumonia in severely burned patients.  J Trauma-injury Infect Crit Care . 1998;  45 383-387
    PubMedGoogle Scholar
  • 48 Olson B, Weinstein R A, Nathan C. Epidemiology of endemic Pseudomonas aerogenosa: why infection control efforts have failed. J Infect Dis .  1984;  150 808
    PubMedGoogle Scholar
  • 49 Bonten M J, Gaillard C A, de Leeuw. Role of colonization of the upper intestinal tract in the pathogenesis of ventilator-associated pneumonia.  Clin Infect Dis . 1997;  24 309-319
    CrossrefPubMedGoogle Scholar
  • 50 Torres A, el-Ebiary M, Gonzalez J. Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation.  Am Rev Respir Dis . 1993;  148 352-357
    CrossrefPubMedGoogle Scholar
  • 51 Bertrand X, Thouverez M, Talon D. Endemicity, molecular diversity and colonization routes of Pseudomonas aeruginosa in intensive care units.  Intens Care Med . 2001;  21 1263-1268
    PubMedGoogle Scholar
  • 52 Bonten M J, Gaillard C A, Johanson Jr G W. Colonization in patients receiving and not receiving topical antimicrobial prophylaxis.  Am J Respir Crit Care Med . 1994;  150 1332-1340
    PubMedGoogle Scholar
  • 53 Caplan E S, Hoyt N J. Nosocomial sinusitis.  JAMA . 1982;  247 639-641
    CrossrefPubMedGoogle Scholar
  • 54 Salord F, Gaussorgues P, Marti-Flinch J. Nosocomial maxillary sinusitis during mechanical ventilation: a prospective comparison of orotracheal versus the nasotracheal route for intubation.  Intens Care Med . 1990;  16 390-393
    PubMedGoogle Scholar
  • 55 Bach A, Boehrer H, Schmidt H. Nosocomial sinusitis in ventilator patients: nasotracheal versus orotracheal intubation.  Anesthesia . 1992;  47 335-339
    PubMedGoogle Scholar
  • 56 Rouby J-J, Laurent P, Gosnach M. Risk factors and clinical relevance of nosocomial maxillary sinusitis in the critically ill.  Am J Respir Crit Care Med . 1994;  150 776-783
    CrossrefPubMedGoogle Scholar
  • 57 Westergren V, Forsum U, Lundgren J. Possible errors in diagnosis of bacterial sinusitis in tracheal intubated patients.  Acta Anaesthesiol Scand . 1994;  38 699-703
    PubMedGoogle Scholar
  • 58 Westergren V, Lundblad L, Forsum U. Ventilator-associated sinusitis: antroscopic findings and bacteriology when excluding contaminants.  Acta Otolaryngol (Stockh) . 1998;  118 574-580
    CrossrefPubMedGoogle Scholar
  • 59 Mayhall C G. International Consensus Conference in Intensive Care Medicine: ICU-acquired pneumonia. American Thoracic Society, European Respiratory Society and European Society of Intensive Care Medicine, Chicago, Illinois, May 23-24, 2002 In: press. 
    Google Scholar
  • 60 Holzapfel L, Chevret S, Madinier G. Influence of long term oro- or nasotracheal intubation on nosocomial maxillary sinusitis and pneumonia: results of a prospective, randomized, clinical trial.  Crit Care Med . 1993;  21 1132-1138
    CrossrefPubMedGoogle Scholar
  • 61 Holzapfel L, Chastang C, Demingeon G. A randomized study assessing the systemic search for maxillary sinusitis in nasotracheally mechanically ventilated patients: influence of nosocomial maxillary sinusitis on the occurrence of ventilator-associated pneumonia.  Am J Respir Crit Care Med . 1999;  159 695-701
    PubMedGoogle Scholar
  • 62 Kollef M H. The prevention of ventilator-associated pneumonia.  N Engl J Med . 1999;  340 627-634
    CrossrefPubMedGoogle Scholar
  • 63 Prod'hom G, Leuenberger P, Loerfer J. Nosocomial pneumonia in mechanically ventilated patients receiving antacid, ranitidine, or sucralfate as prophylaxis for stress ulcer: a randomized controlled trial.  Ann Intern Med . 1994;  120 620-653
    PubMedGoogle Scholar
  • 64 Tryba M. The gastropulmonary route of infection: fact or fiction?.  Am J Med . 1991;  S135-S146
    PubMedGoogle Scholar
  • 65 Dricks M R, Craven D E, Celli B R. Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers: the role of gastric colonization.  N Engl J Med . 1987;  317 1376-1382
    PubMedGoogle Scholar
  • 66 Bonten M J, Gaillard C A, de Leeuw W P. The role of intragastric acidity and stress ulcer prophylaxis on colonization and infection in mechanically ventilated ICU patients: a stratified, randomized, double-blind study of sucralfate versus antacids.  Am J Respir Crit Care Med . 1995;  152 1825-1834
    PubMedGoogle Scholar
  • 67 Cook D J, Guyatt G, Marshall J. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation: Canadian critical care trials groups.  N Engl J Med . 1998;  338 791-797
    CrossrefPubMedGoogle Scholar
  • 68 Cook D J, Reeve B K, Guyatt G. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analysis.  JAMA . 1996;  275 308-314
    CrossrefPubMedGoogle Scholar
  • 69 Bonten M J, Gaillard C A, van Tiel H F. The stomach is not the source for colonization of the upper respiratory tract and pneumonia in ICU patients.  Chest . 1994;  105 878-884
    CrossrefPubMedGoogle Scholar
  • 70 George D L, Falk P S, Wunderink R G. Epidemiology of ventilator-acquired pneumonia based on protected bronchoscopic sampling.  Am J Respir Crit Care Med . 1998;  158 1839-1847
    PubMedGoogle Scholar
  • 71 Kollef M H. The role of selective digestive decontamination on mortality and respiratory tract infections: a meta-analysis.  Chest . 1994;  105 1101-1108
    PubMedGoogle Scholar
  • 72 D'Amico R, Pifferi S, Leonetti C, et al Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomized controlled trials. Brit Med J .  1998;  316 1275-1285
    PubMedGoogle Scholar
  • 73 Jacobs S, Chang R W, Lee B. Continuous enteral feeding: a major cause of pneumonia among ventilated intensive unit patients.  J Parenteral Enteral Nutr . 1990;  14 353-356
    PubMedGoogle Scholar
  • 74 File Jr M T, Tran J S, Thompson Jr B R. An outbreak of Pseudomonas aeruginosa ventilator-associated pneumonia respiratory tract infections due to contaminated food dye: further evidence of the significance of gastric colonization preceding nosocomial pneumonia.  Infect Control & Hosp Epidemiol . 1995;  16 417-418
    PubMedGoogle Scholar
  • 75 Drakulovic M, Torres A, Brauer T. Supine body position as a risk factor for nosocomial pneumonia in mechanical ventilated patients: a randomized trial.  Lancet . 1999;  354 1851-1858
    CrossrefPubMedGoogle Scholar
  • 76 Markowicz P, Woolf M, Djedaini K. Multicenter prospective study of ventilator-associated pneumonia during acute respiratory distress syndrome.  Am J Respir Crit Care Med . 2000;  161 1942-1948
    PubMedGoogle Scholar
  • 77 Ferrer M, Bauer T, Torres A. Gastro-esophageal reflux and micro aspiration to the lower airways in intubated patients; impact of nasogastric size.  Ann Intern Med . 1999;  130 991-994
    CrossrefPubMedGoogle Scholar
  • 78 Rumbak M J, Mayhall C G. Nosocomial pneumonia in the critically ill.  Crit Care Med . 1992;  20 905-906
    PubMedGoogle Scholar
      >