Mechanisms of airway colonization and infection

The understanding of the pathogenesis of nosocomial pneumonia is absolutely necessary for the rational comprehension of risk factors involved with this intrahospital infection. The pathogenic scheme recently recommended by the Centers for Disease Control ( T.ab.!iD §.L.§/: 1994) is shown in Fig 1. 'Abnormal' colonization of the oropharynx and the gastric reservoir and the subsequent aspiration of their contents to lower airways in patients whose mechanical, cellular, and humoral defenses are impaired may lead to the development of nosocomial pneumonia (Table 1). The inoculation of micro-organisms to the oropharynx or lower airways is another related mechanism. An alternative mechanism may be the bacterial translocation of enteric bacteria and their products from ischemic gut to lung. Bacteremic lung metastasis is the pathogenic mechanism in some cases of nosocomial pneumonia (Ram..p.h.§J 1994).

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Fig. 1 Pathogenic scheme recommended by the Centers for Disease Control

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Table 1 Pathogenesis scheme recommended by the Centers for Disease Control.

Abnormal oropharyngeal and gastric colonization

The majority of cases of nosocomial pneumonia are the result of aspiration of oropharyngeal and gastric contents to the lower airways. The 'abnormal' colonization of the oropharynx is a clear risk factor for the development of nosocomial pneumonia. Gram-negative bacillary colonization of the oropharynx increases from 35 per cent in moderately ill patients to 73 per cent in critically ill patients. Furthermore, the rate of nosocomial pneumonia is almost eight times higher in colonized compared with non-colonized patients. Intimal mechanisms for 'abnormal' oropharyngeal colonization are the release of oral proteases and the loss of fibronectin which is necessary to prevent the adherence of Gram-negative bacilli to the epithelial cells of the oropharyngeal mucosal surface. Antibiotic therapy seems to be one of the main mechanisms related to oropharyngeal colonization.

Transcolonization from contiguous structures to the oropharynx is an important feature in oropharyngeal colonization. Reservoirs such as dental plaque, sinuses, and nasal mucosa could be the initial reservoir for oropharyngeal colonization. The presence of sinusitis as a risk factor for pneumonia has been reported but is not widely appreciated. The presence of sinusitis has been linked to the nasal placement and duration of endotracheal and gastric intubation. Nosocomial pneumonia occurs significantly more frequently in the patients with maxillary sinusitis.

Gastric colonization as a reservoir for retrograde oropahryngeal colonization or direct tracheal colonization was detected some years ago. The stomach is usually sterile, but at alkaline pH (>4) may contain more than 100 million organisms/ml. Increases in gastric colonization may occur with advanced age, achlorhydria, alterations in gastric juice secretion, and particularly with treatment with antacids or H 2 blockers prescribed for stress bleeding prophylaxis in critically ill patients. Although still controversial, several randomized studies have shown that rates of nosocomial pneumonia, particularly in mechanically ventilated patients, are decreased when sucralfate is given rather than antacid or H 2 blockers. The absence of gastric alkalinization with sucralfate and its antibacterial effect may explain the protective effect of this drug against nosocomial pneumonia ( Craven ef a/ 1994).

Another factor related to the existence of bacteria in the gastric cavity is the presence of bilirubin in gastric contents. Indeed, the presence and amount of bilirubin in the stomach is related to a decrease in duodenal motility. Aspiration

Aspiration frequently occurs in healthy people during sleep and is one of the final steps in the development of nosocomial pneumonia. The amounts of aspiration and of bacterial inoculum are variables related to this pathogenic mechanism of nosocomial pneumonia. Overall, factors that promote alteration of conciousness favor aspiration. It is important to remember that even the presence of an endotracheal tube may not avoid the risk of aspiration between the tracheal tube cuff and the tracheal wall (Rejloefa/ 1997). Aspiration of gastric contents to lower airways is favored by the supine position and by the presence of a nasogastric tube.

Nasogastric intubation is a risk factor for nosocomial pneumonia since it indirectly favors several risk factors for pneumonia: oropharyngeal colonization, gastroesophageal reflux, bacterial migration, and sinusitis. Gastroesophageal reflux is a constant feature in mechanically ventilated patients with a nasogastric tube in place and potentially may increase oropharyngeal colonization. Reducing the size of nasogastric tubes would have a beneficial effect in reflux. Maintaining the patient in the upright position reduces the amount of aspiration of gastric contents to the lower airways.

An endotracheal tube 'bypasses' the natural mechanical host defenses and obviously facilitates the entry of bacteria into the lung. Also, leakage around the cuff allows the pooled secretions accumulated above the cuff to enter the trachea. Suction to remove subglottic secretions is an effective prophylactic mechanism for ventilator-associated pneumonia. The importance of careful airway management, including maintenance of adequate intracuff pressure, in reducing the risk of pneumonia should be emphasized (Relloela/ 1996).

Biofilm formation in endotracheal tubes and the dislodgement of these biofilms with bacteria to the lower airways is another risk factor suggested to be implicated in ventilator-associated pneumonia.

Bacterial translocation

Bacterial or toxin translocation from gut to lung is an alternative mechanism for the development of nosocomial pneumonia. Intramucosal gastric ischemia measured by tonometry was invariably present in a group of critically ill patients with nosocomial pneumonia and was also an independent risk factor in a multivariate analysis. More prospective investigations are needed to confirm that intramucosal gastric ischemia is a risk factor for the development of nosocomial pneumonia.

Aerosols or contamination of respiratory equipment

External colonization by aerosol inoculation or contamination of respiratory equipment is a well-known mechanism for respiratory nosocomial transmission. Among several types of equipment, nebulizers are the most dangerous since the size of particles produced easily bypasses the lower-airway defenses.

In mechanical ventilators, excessive manipulation of tubing and the formation of water condensate are risk factors for nosocomial pneumonia. Water humidifiers favor the formation of water condensate in ventilator tubing. Heat moisture exchangers that recycle exhaled heat and moisture eliminate water condensate.

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