• 17
    Mar
  • Pneumonia in the critically ill hospitalized patient: part 4

The patient discussed today has multiple risk factors for both upper and lower airway colonization (Table 1). These included his serious degree of underlying illness, recent surgery, the use of multiple antibiotics, endotracheal intubation and tracheostomy, malnutri­tion, the use of corticosteroids, recurrent hypotensive episodes, and the use of histamine type-2 receptor blocking agents for the prophylaxis of gastrointestinal bleeding. Each of these factors increased the risk of airway colonization through a variety of mechanisms.

Antibiotics can increase the risk of infection by interfering with the normal flora in both the upper and lower respiratory tract. The normal upper respiratory tract rarely harbors Gram-negative bacte­ria and is usually colonized by Gram-positive organ­isms, particularly anaerobes, which may “interfere” with the growth of Gram-negative organisms. It has been conceptualized that the normal flora of the upper airway occupy bacterial binding sites in the oropha­ryngeal muscosa and, thereby, block subsequent colo­nization by Gram-negative bacteria. This type of interference can be eliminated with the use of sys­temic antibiotics. A similar mechanism may also apply in the lower airway, although in most individuals the lower airway does not have normal flora and is ster­ile.

Endotracheal intubation can increase the risk of upper and lower airway colonization and pneumonia. Patients with tracheostomy have nearly a 70 percent incidence of nosocomial pneumonia and this is largely related to two factors. First, patients with tracheos­tomy have the capacity for organisms to directly enter the lower respiratory tract, thereby bypassing upper airway defenses. In addition, the presence of a trach­eostomy or an endotracheal tube may traumatize the tracheobronchial mucosa and alter its integrity, making it more susceptible to invasion and colonization. Corticosteroids may predispose to colonization by interfering with a variety of host defense mecha­nisms. Histamine type 2 (H2) blockers similarly may predispose to colonization by the mechanisms to be discussed by Dr. Craven. In our own studies of mechanically ventilated patients, it has been observed that Pseudomonas species colonization of the lower airway was more common in patients receiving H2- blockers than in patients who did not receive this therapy. kamagra tablets

Table 1- Risk Factors for Gram-Negative Airway Colonization

Oropharynx

Lower Respiratory
Tract

Antibiotic
therapy

Antibiotic
therapy

Azotemia*

Chronic
bronchitis

Coma

Ciliary
dysfunction

Diabetes

Corticosteroid
therapy

Hypotension

Bronchiectasis

Advanced age

Cystic fibrosis

Endotracheal
intubation*

Endotracheal
intubation*

Pre-existing lung
disease

Tracheostomy*

Smoking*

Malnutrition*

Surgery*

Surgery*

Serious illness*

Acute lung injury

Malnutrition*

Viral infection*

Gastric
acid-neutralization

Smoking

Gastric
acid-neutralization

The major pathogenetic mechanism that unifies many of the risk factors for upper and lower airway colonization involves the cell-cell interaction termed bacterial adherence. At multiple mucosal sites throughout the body, the binding of bacteria to the epithelial surface has been demonstrated to be an important mechanism that leads to colonization. In the respiratory tract, bacterial adherence has been demonstrated to mediate Gram-negative colonization of both the upper and the lower airway. Many of the risk factors for airway colonization have been shown to act by enhancing the ability of respiratory epithelial cells to bind bacteria, thereby allowing bacteria to establish a foothold on the respiratory mucosa (Table 1). Studies to date have demonstrated that general surgery, renal failure, malnutrition and cardiac bypass surgery all have the ability to make oropharyngeal epithelial cells express more binding sites for Gram-negative bacteria.

In studies by Johanson and colleagues, it has been demonstrated that patients whose lungs became col­onized after general surgery had a serial rise in the ability of their buccal epithelial cells to bind bacteria. Such a serial rise was not observed in patients who did not develop colonization following general surgery. The mechanism whereby serious illness and systemic insult increase the number of binding sites on oral epithelial cells has been evaluated by the same inves­tigators. In these studies, it was shown that certain critically ill patients elaborate proteases in their sali­vary secretions which have the capacity to digest fibronectin from the cell surface. Fibronectin ap­pears to be a blocking glycoprotein which covers epithelial cell receptors for Gram-negative bacteria. With the release of oral proteases, fibronectin is removed from the buccal epithelial surface, thereby exposing more epithelial receptors for subsequent bacterial binding. It is yet unknown whether similar mechanisms operate in the lower respiratory tract. However, it has been shown that patients with trach­eostomy, colonized by Pseudomonas aeruginosa, had an overall higher degree of tracheal cell binding capacity than did tracheostomized patients who were not colonized by Pseudomonas aeruginosa. In addi­tion, patients with the highest degree of tracheal cell adherence tended to have the highest levels of neutro­phil elastase in their tracheal secretions. Thus, it is possible that proteases in high concentrations, in some manner mediated the increased adherence to tracheal epithelial cells that was seen in patients colonized in the lower airway by Pseudomonas species. viagra 50 mg

Malnutrition is one host factor that has been related to both colonization and increases in adherence to both oral and tracheal epithelial cells. Higuchi and colleagues demonstrated, in an animal model, that with progressive declines in animal weight, there was a serial rise in the ability of buccal epithelial cells to bind bacteria. In addition, among tracheostomy patients, those with the most severe nutritional im­pairment tended to have the highest degree of tracheal cell adherence. In patients with endotracheal intu­bation who were receiving mechanical ventilation, it has also been shown that patients who were severely malnourished had a greater likelihood to develop lower respiratory tract colonization by Pseudomonas species than intubated patients who were better nourished.

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