The Pathogenesis of Nosocomial Pneumonia in Mechanically Ventilated Patients

  • M. J. M. Bonten
  • C. A. Gaillard
  • G. Ramsay
Conference paper
Part of the Yearbook of Intensive Care and Emergency Medicine book series (YEARBOOK, volume 1995)

Abstract

Among mechanically ventilated patients, pneumonia is an important infection associated with increased morbidity and mortality [1–6]. Due to its association with mechanical ventilation, this infection has also been called ventilator-associated pneumonia (VAP), although this falsely suggests a predominant causative role of the ventilator in its pathogenesis. Many studies elucidating pathogenic pathways, therapeutic options, prevention and accurate diagnosis of VAP have been performed over the last twenty years. The pathogens causing VAP have been assumed to be from endogenous origin, and current hypothesis suggests that the gastropulmonary route of colonization is of major importance in the pathogenesis of VAP [7, 8]. The gastropulmonary route assumes that enteric microorganisms colonize the stomach, migrate to the oropharynx and eventually reach the lungs of mechanically ventilated patients by aspiration. Although the gastropulmonary route has been assumed to be of major importance, other routes of colonization, like exogenous colonization and the rectopulmonary route, may also lead to the development of VAP. The possible role of these routes will be discussed as well.

Keywords

Catheter Pneumonia Acidity Bacillus Histamine 

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References

  1. 1.
    Torres A, Aznar R, Gatell JM, et al (1990) Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. Am Rev Respir Dis 142: 523–528PubMedCrossRefGoogle Scholar
  2. 2.
    Jimenez P, Torres A, Rodriguez-Roisin R, et al (1989) Incidence and etiology of pneumonia acquired during mechanical ventilation. Crit Care Med 17: 882–886PubMedCrossRefGoogle Scholar
  3. 3.
    Craven DE, Kunches LM, Kilinsky V, Lichtenberg DA, Make BJ, McCabe WR (1986) Risk factors for pneumonia and fatality in patients receiving continuous mechanical ventilation. Am Rev Respir Dis 113: 792–796Google Scholar
  4. 4.
    Leu HS, Kaiser DL, Mori M, Woolson RF, Wenzel RP (1989) Hospital-acquired pneumonia. Attributable mortality and morbidity. Am J Epidemiol 129: 1258–1267PubMedGoogle Scholar
  5. 5.
    Celis R, Torres A, Gatell JM, Almela M, Rodriguez-Roisin R, Agusti-Vidal A (1988) Nosocomial pneumonia. A multivariate analysis of risk and prognosis. Chest 93: 318–324PubMedCrossRefGoogle 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: 281–288PubMedCrossRefGoogle Scholar
  7. 7.
    Heyland D, Mandell LA (1992) Gastric colonization by gram-negative bacilli and nosocomial pneumonia in the intensive care unit patients: Evidence for causation. Chest 101: 187–193PubMedCrossRefGoogle Scholar
  8. 8.
    Tryba M (1991) The gastropulmonary route of infection — fact or fiction? Am J Med 91 (Suppl 2A): 135–146CrossRefGoogle Scholar
  9. 9.
    Fagon JY, Chastre J, Domart Y, et al (1991) Nosocomial pneumonia in patients receiving continuous mechanical ventilation. Am Rev Respir Dis 139: 877–884Google Scholar
  10. 10.
    Rello J, Quintana E, Ausina V, et al (1991) Incidence, etiology and outcome of nosocomial pneumonia in mechanically ventilated patients. Chest 100: 439–444PubMedCrossRefGoogle Scholar
  11. 11.
    Rello J, Ausina V, Castella J, Net A, Prats G (1992) Nosocomial respiratory tract infections in multiple trauma patients. Influence of level of consciousness with implications for therapy. Chest 102: 525–529PubMedCrossRefGoogle Scholar
  12. 12.
    Driks MR, Craven DE, Celli BR, et al (1987) Nosocomial pneumonia in intubated patients given sucralfate as compared with antacids or histamine type 2 blockers. N Engl J Med 317: 1376–1382PubMedCrossRefGoogle Scholar
  13. 13.
    Kerver AJH, Rommes JH, Mevissen-Verhage EAE, et al (1988) Prevention of colonization and infection in critically ill patients: A prospective randomized study. Crit Care Med 16: 1087–1093PubMedCrossRefGoogle Scholar
  14. 14.
    Fagon JY, Chastre J, Hance AJ, Domart Y, Trouillet JL, Gibert C (1993) Evaluation of clinical judgement in the identification and treatment of nosocomial pneumonia in ventilated patients. Chest 103: 547–553PubMedCrossRefGoogle Scholar
  15. 15.
    Torres A, De la Bella Casa JP, Xaubet A, et al (1989) Diagnostic value of quantitative cultures of bronchoalveolar lavage and telescoping plugged catheters in mechanically ventilated patients with bacterial pneumonia. Am Rev Respir Dis 140: 306–310PubMedCrossRefGoogle Scholar
  16. 16.
    Scheid WM, Mandell GL (1991) Nosocomial pneumonia: Pathogenesis and recent advances in diagnosis and therapy. Rev Infect Dis 13 (Suppl 9): 743–751Google Scholar
  17. 17.
    Horan T, Culver D, Jarvis W, et al (1988) Pathogens causing nosocomial infections. Antimicrob Newslett 5: 65–67CrossRefGoogle Scholar
  18. 18.
    Bartlett JG, O’Keefe P, Tally FP, Louie TJ, Gorbach SL (1986) Bacteriology of hospital acquired pneumonia. Arch Intern Med 146: 868–871PubMedCrossRefGoogle Scholar
  19. 19.
    Johanson WG, Pierce AK, Sanford JP (1969) Changing pharyngeal bacterial flora of hospitalized patients. N Engl J Med 281: 1137–1140PubMedCrossRefGoogle Scholar
  20. 20.
    Johanson WG, Pierce AK, Sanford JP, Thomas GD (1972) Nosocomial respiratory infections with gram-negative bacilli: The significance of colonization of the respiratory tract. Ann Intern Med 77: 701–706PubMedGoogle Scholar
  21. 21.
    Torres A, El-Ebiary M, Gonzalez J, et al (1993) Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. Am Rev Respir Dis 148: 352–357PubMedGoogle Scholar
  22. 22.
    Schwarz SN, Dowling JN, Benkovic C, DeQuittner-Buchanan M, Prostko T, Yee RB (1978) Sources of gram-negative bacilli colonizing the trachea of intubated patients. J Infect Dis 138: 227–231CrossRefGoogle Scholar
  23. 23.
    Daschner F, Reuschenbach K, Pfisterer J, et al (1987) The influence of stress ulcer prophylaxis on the incidence of pneumonia in artifically ventilated patients. Anaesthesist 36: 9–18PubMedGoogle Scholar
  24. 24.
    Torres A, Serra-Batlles J, Ros E, et al (1992) Pulmonary aspiration of gastric contents in patients receiving mechanical ventilation: The effect of body position. Ann Intern Med 116: 540–543PubMedGoogle Scholar
  25. 25.
    Reinarz JA, Pierce AK, Mays BB, et al (1967) The potential role of inhalation therapy equipment in nosocomial pulmonary infection. J Clin Invest 44: 831–839CrossRefGoogle Scholar
  26. 26.
    McNamara MJ, Hill MC, Balows A, et al (1967) A hospital outbreak of Klebsiella pneumonia from inhalation therapy with contaminated aerosol solutions. Am Rev Respir Dis 95: 454–460Google Scholar
  27. 27.
    Du Moulin, Paterson DG, Hedley-Whyte J, Lisbon A (1982) Aspiration of gastric bacteria in antacid-treated patients: A frequent cause of postoperative colonisation of the airway. Lancet 1: 242–245PubMedGoogle Scholar
  28. 28.
    Hillman KM, Riordan T, O’Farrel SM, Tabaqchal S (1982) Colonization of gastric contents in critically ill patients. Crit Care Med 10: 444–447PubMedCrossRefGoogle Scholar
  29. 29.
    Garvey BM, McCambley JA, Tuxen DV (1989) Effects of gastric alkalization on bacterial colonization in critically ill patients. Crit Care Med 17: 211–216PubMedCrossRefGoogle Scholar
  30. 30.
    Torres A, El-Ebiary M, Gonzalez J, et al (1993) Gastric and pharyngeal flora in nosocomial pneumonia acquired during mechanical ventilation. Am J Respir Crit Care Med 148: 352–357Google Scholar
  31. 31.
    Caballero GA, Ausman RK, Quebbeman EJ, Schulte WJ, Lin L (1990) Gastric secretion pH measurement: What you see is not what you get! Crit Care Med 18: 396–399PubMedCrossRefGoogle Scholar
  32. 32.
    Dobkin ED, Valcour A, McCloskey CR, et al (1990) Does pH paper accurately reflect gastric pH? Crit Care Med 18: 985–988PubMedCrossRefGoogle Scholar
  33. 33.
    Fimmel CJ, Etienne A, Cilufo A, et al (1985) Long-term ambulatory gastric pH monitoring: Validation of a new method and effect of H2-antagonists. Gastroenterology 88: 1842–1851PubMedGoogle Scholar
  34. 34.
    Inglis TJJ, Sheratt MJ, Sproat LJ, Gibson JS, Hawkey PM (1993) Gastroduodenal dysfunction and bacterial colonisation of the ventilated lung. Lancet 341: 911–913PubMedCrossRefGoogle Scholar
  35. 35.
    Reusser P, Zimmerli W, Scheidegger D, Marbet GA, Buser M, Klaus G (1989) Role of gastric colonization in nosocomial infections and endotoxemia: A prospective study in neurosurgical patients on mechanical ventilation. J Infect Dis 160: 414–421PubMedCrossRefGoogle Scholar
  36. 36.
    Cade JF, McOwat E, Siganporia R, Keighly C, Presneill J, Sinickas V (1992) Uncertain relevance of gastric colonization in the seriously ill. Intensive Care Med 18: 210–217PubMedCrossRefGoogle Scholar
  37. 37.
    Bonten MJM, Gaillard CA, van Tiel FH, van der Geest S, Stobberingh EE (1994) The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest 105: 878–884PubMedCrossRefGoogle Scholar
  38. 38.
    McCarthy DM (1991) Sucralfate. N Engl J Med 325: 1017–1025PubMedCrossRefGoogle Scholar
  39. 39.
    Tryba M (1987) Risk of acute stress bleeding and nosocomial pneumonia in ventilated intensive care patients: Sucralfate versus antacids. Am J Med 83 (Suppl 3B): 117–124PubMedCrossRefGoogle Scholar
  40. 40.
    Laggner AN, Lenz K, Graninger W, et al (1988) Stressblutungsprophylaxe auf einer internen Intensivstation: Sucralfat versus Lanitidin. Anaesthesist 37: 704–710PubMedGoogle Scholar
  41. 41.
    Kappstein I, Schulgen G, Friedrich T, et al (1991) Incidence of pneumonia in mechanically ventilated patients treated with sucralfate or cimetidine as prophylaxis for stress bleeding: Bacterial colonization of the stomach. Am J Med 91 (Suppl 2A): 125S–131SPubMedCrossRefGoogle Scholar
  42. 42.
    Simms HH, DeMaria E, McDonald L, Peterson D, Robinson A, Burchard KW (1991) Role of gastric colonization in the development of pneumonia in critically ill trauma patients: Results of a prospective randomized trial. J Trauma 31: 531–537PubMedCrossRefGoogle Scholar
  43. 43.
    Eddlestone JM, Vohra A, Scott P, et al (1991) A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care patients. Crit Care Med 19: 1491–1496CrossRefGoogle Scholar
  44. 44.
    Prod’hom G, Leuenberger P, Koerfer J, et al (1994) Nosocomial pneumonia in mechanically ventilated patients receiving antacids, ranitidine, or sucralfate as prophylaxis for stress ulcer. A randomised trial. Ann Intern Med 120: 653–662PubMedGoogle Scholar
  45. 45.
    Moore JG, Englert E (1970) Circadian rythm of gastric acid secretion in man. Nature 226: 1261–1262PubMedCrossRefGoogle Scholar
  46. 46.
    Tryba M (1991) Sucralfate versus antacids or H2-antagonists for stress ulcer prophylaxis: A meta-analysis on efficacy and pneumonia rate. Crit Care Med 19: 942–949PubMedCrossRefGoogle Scholar
  47. 47.
    Tryba MY, Mantey-Stiers F (1987) Antibacterial activity of sucralfate in human gastric juice. Am J Med 83 (Suppl 3B): 125–127PubMedCrossRefGoogle Scholar
  48. 48.
    Daschner F, Kappstein I, Engels I (1987) Antibacteriell Aktivität von Sucralfat in kunstlichem Magensaft. Intensivmed 83: 163–166Google Scholar
  49. 49.
    Bergmans D, Bonten M, Gaillard C, van Tiel F, van der Geest S, Stobberingh E (1994) In vitro antibacterial activity of sucralfate. Eur J Clin Microbiol Infect Dis 13: 615–620PubMedCrossRefGoogle Scholar
  50. 50.
    Pingleton SK, Hinthorn DR, Liu C (1986) Enteral nutrition in patients receiving mechanical ventilation. Am J Med 80: 827–832PubMedCrossRefGoogle Scholar
  51. 51.
    Jacobs S, Chang RWS, Lee B, Bartlett FW (1990) Continuous enteral feeding: A major cause of pneumonia among ventilated intensive care unit patients. J Parent Enteral Nutr 14: 353–356CrossRefGoogle Scholar
  52. 52.
    Ibanez J, Penafiel A, Raurich JM, Marse P, Jorda R, Mata F (1992) Gastroesophageal reflux in intubated patients receiving enteral nutrition: Effect of supine and semirecumbent positions. J Parent Enteral Nutr 16: 419–422CrossRefGoogle Scholar
  53. 53.
    Stoutenbeek CP, Van Saene HKF, Miranda DR, Zandstra DF (1984) The effect of selective decontamination of the digestive tract on colonization and infection rate in multiple trauma patients. Intensive Care Med 10: 185–192PubMedCrossRefGoogle Scholar
  54. 54.
    Aerdts SJA, Clasener HAL, Van Dalen R, Van Lier HJJ, Vollaard EJ, Festen J (1991) Antibiotic prophylaxis of respiratory tract infection in mechanically ventilated patients. Chest 100: 783–791PubMedCrossRefGoogle Scholar
  55. 55.
    Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S (1992) A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. N Engl J Med 326: 594–599PubMedCrossRefGoogle Scholar
  56. 56.
    Hammond JMJ, Potgieter PD, Saunders GL, Forder AA (1992) Double-blind study of selective decontamination of the digestive tract in intensive care. Lancet 340: 5–9PubMedCrossRefGoogle Scholar
  57. 57.
    Cockerill FR III, Muller SR, Anhalt JP, et al (1992) Prevention of infection in critically ill patients by selective decontamination of the digestive tract. Ann Intern Med 117: 545–553PubMedGoogle Scholar
  58. 58.
    Gastinne H, Wolff M, Lachatre G, Boiteau R, Savy FP (1991) Antibiotic levels in bronchial tree and in serum, during selective digestive decontamination. Intensive Care Med 17: 215–218PubMedCrossRefGoogle Scholar
  59. 59.
    Stoutenbeek CP, Van Saene HKF, Miranda DR, Zandstra DF, Langrehr D (1987) The effect of oropharyngeal decontamination using topical nonabsorbable antibiotics on the incidence of nosocomial respiratory infections in multiple trauma patients. J Trauma 27: 357–364PubMedCrossRefGoogle Scholar
  60. 60.
    Brun-Buisson C, Legrand P, Rauss A, et al (1989) Intestinal decontamination for control of nosocomial multiresistant gram-negative bacilli: Study of an outbreak in an intensive care unit. Ann Intern Med 110: 873–881PubMedGoogle Scholar
  61. 61.
    Rodriguez-Roldan JM, Altuna-Cuesta A, Lopez A, et al (1990) Prevention of nosocomial lung infection in ventilated patients: Use of an antimicrobial pharyngeal nonabsorbable paste. Crit Care Med 18: 1239–1242PubMedCrossRefGoogle Scholar
  62. 62.
    Pugin J, Auckenthaler R, Lew D, Suter PM (1991) Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. JAMA 265: 2704–2710PubMedCrossRefGoogle Scholar
  63. 63.
    Kropec A, Huebner J, Riffel M, et al (1993) Exogenous or endogenous reservoirs of nosocomial Pseudomonas aeruginosa and Staphylococcus aureus infections in a surgical intensive care unit. Intensive Care Med 19: 161–165PubMedCrossRefGoogle Scholar
  64. 64.
    Murthy SK, Baltch AL, Smith RP, et al (1989) Oropharyngeal and fecal carriage of Pseudomonas aeruginosa in hospital patients. J Clin Microbiol 27: 35–40PubMedGoogle Scholar
  65. 65.
    Noone MR, Pitt TL, Bedder M, Hewlett AM, Rogers KB (1983) Pseudomonas aeruginosa colonisation in an intensive therapy unit: Role of cross infection and host factors. Br Med J 286: 341–344CrossRefGoogle Scholar
  66. 66.
    Flynn DM, Weinstein RA, Nathan C, Gaston MA, Kabins SA (1988) Patients’ endogenous flora as the source of “nosocomial” Enterobacter in cardiac surgery. J Infect Dis 156: 363–368CrossRefGoogle Scholar
  67. 67.
    Wells FC, Newsom SWB, Rowlands C (1983) Wound infection in cardiothoracic surgery. Lancet 1: 1209–1210PubMedCrossRefGoogle Scholar
  68. 68.
    Farmer JJ III, Weinstein RA, Zierdt CH, Brokopp CD (1982) Hospital outbreaks caused by Pseudomonas aeruginosa: Importance of serogroup 011. J Clin Microbiol 16: 266–270PubMedGoogle Scholar
  69. 69.
    Cefai C, Richards J, Gould FK, McPeake P (1990) An outbreak of acinetobacter respiratory tract infection resulting from incomplete disinfection of ventilatory equipment. J Hosp Infect 15: 177–182PubMedCrossRefGoogle Scholar
  70. 70.
    Freeman R, McPeake PK (1982) Acquisition, spread, and control of Pseudomonas aeruginosa in a cardiothoracic intensive care unit. Thorax 37: 732–736PubMedCrossRefGoogle Scholar
  71. 71.
    Craven DE, Conolly MG, Livhtenberg DA (1982) Contamination of mechanical ventilators with tubing changes every 24 or 48 hours. N Engl J Med 306: 1505–1508PubMedCrossRefGoogle Scholar
  72. 72.
    Smith PW, Massanari RM (1977) Room humidifiers as the source of acinetobacter infections. JAMA 237: 795–798PubMedCrossRefGoogle Scholar
  73. 73.
    Fagerman KE, Paauw JA, Dean RE (1985) Bacterial contamination of enteral solutions. J Parent Enteral Nutr 9: 378CrossRefGoogle Scholar
  74. 74.
    Levy J, Van Laethem Y, Verhaegen G, Perpete C, Bytzler JP, Wenzel RP (1989) Contaminated enteral nutrition solutions as a cause of nosocomial bloodstream infection: A study using plasmid fingerprinting. J Parent Enteral Nutr 13: 228–234CrossRefGoogle Scholar
  75. 75.
    Thurn J, Crossley K, Gerdts A, Maki M, Johnson J (1990) Enteral hyperalimentation as a source of nosocomial infection. J Hosp Infection 15: 203–217CrossRefGoogle Scholar
  76. 76.
    Weinstein RA, Nathan C, Gruenfelder R, Kabins SA (1980) Endemic aminoglycoside resistance in gram-negative bacilli: Epidemiology and mechanisms. J Infect Dis 141: 338–345PubMedCrossRefGoogle Scholar
  77. 77.
    Gaynes RP, Weinstein RA, Smith J, Carman M, Kabins SA (1983) Control of aminoglycoside resistance by barrier precautions. Infection Control 4: 221–224PubMedGoogle Scholar
  78. 78.
    Maki DG (1978) Control of colonization and transmission of pathogenic bacteria in the hospital. Ann Intern Med 89: 777–780PubMedGoogle Scholar
  79. 79.
    Olson B, Weinstein RA, Nathan C, Chamberlin W, Kabins SA (1989) Epidemiology of endemic Pseudomonas aeruginosa: Why infection control efforts have failed. J Infect Dis 150: 808–816CrossRefGoogle Scholar
  80. 80.
    Widmer AF, Wenzel RP, Trilla A, Bale MJ, Jones RN, Doebbeling BN (1993) Outbreak of Pseudomonas aeruginosa infections in a surgical intensive care unit: Probable transmission via hands of a health care worker. Clin Infect Dis 16: 372–376PubMedCrossRefGoogle Scholar
  81. 81.
    Mayer JA, Dubbert PM, Miller M, Burkett PA, Chapman SW (1986) Increasing handwashing in an intensive care unit. Infect Control 7: 259–262PubMedGoogle Scholar
  82. 82.
    Maki DG, Alvarado CJ, Hassemer CA, Zilz MA (1982) Relation of the inanimate hospital environment to endemic nosocomial infection. N Engl J Med 307: 1562–1566PubMedCrossRefGoogle Scholar
  83. 83.
    Massanari RM, Hierholzer WJ Jr (1984) A crossover comparison of antiseptic soaps on nosocomial infection rates in intensive care units. Am J Infect Control 12: 247–248Google Scholar
  84. 84.
    Doebbeling BN, Stanley GL, Sheetz CT, et al (1992) Comparative efficacy of alternative hand-washing agents in reducing nosocomial infections in intensive care units. N Engl J Med 327: 88–93PubMedCrossRefGoogle Scholar
  85. 85.
    Albert RK, Condie F (1981) Hand-washing patterns in medical intensive care units. N Engl J Med 304: 1465–1466PubMedCrossRefGoogle Scholar
  86. 86.
    Quraishi ZA, McGuckin M, Blais FX (1984) Duration of handwashing in intensive care units: A descriptive study. Am J Infect Control 12: 83–87PubMedCrossRefGoogle Scholar
  87. 87.
    Graham M (1990) Frequency and duration of handwashing in an intensive care unit. Am J Infect Control 18: 77–81PubMedCrossRefGoogle Scholar
  88. 88.
    Bonten MJM, Gaillard CA, Johanson WGM, van Tiel FH, van der Geest S, Stobberingh EE (1995) Colonization in patients receiving and not-receiving topical antimicrobial prophylaxis. Am J Resp Crit Care Med (in press)Google Scholar
  89. 89.
    Frank U, Lenz W, Damrath E, Kappstein I, Daschner FD (1989) Nasal carriage of Staphylococcus aureus treated with topical mupirocin in a children’s hospital. J Hosp Infect 13: 117–120PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • M. J. M. Bonten
  • C. A. Gaillard
  • G. Ramsay

There are no affiliations available

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