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  • Pneumonia in the critically ill hospitalized patient: part 5

In studies of bacterial adherence, there has been the consistent observation, in normal individuals and in critically ill patients, that tracheal cells have a greater capacity to bind Pseudomonas aeruginosa than do buccal epithelial cells. The clinical relevance of these findings may relate to the occurrence of tissue “tropisms,” or preferences, of Pseudomonas aeruginosa in the human respiratory tract. In other words, if Pseudomonas aeruginosa binds to tracheal cells more avidly than it binds to buccal cells, then possibly Pseudomonas aeruginosa would preferentially colonize the lower airway rather than the upper airway, if the organism has access to both sites simultaneously. Such a situation does exist in patients with tracheostomy and in patients with endotracheal intubation. In both of these populations, colonization studies have dem­onstrated that Pseudomonas species colonized the lower airway more frequently and persistently than the upper airway. The patient discussed today did 174 not have bacterial adherence directly measured. How­ever, it is likely that many clinical factors did increase his tracheal cell capacity to bind Pseudomonas aeru­ginosa and, thereby, led to persistent lower airway colonization by Pseudomonas aeruginosa. The persist­ence of colonization by Pseudomonas aeruginosa in such patient may be related to multiple factors. The patient was severely malnourished and if malnutrition increased tracheal cell binding capacity for bacteria, then Pseudomonas colonization would persist until the malnutrition was reversed. In addition, with colonization, airway inflammation is present and neu­trophils in inflammatory secretions can release elas­tase which can, in turn, interfere with the local protective function of IgA and further predispose to airway colonization. A vicious circle of colonization begetting more colonization is quite likely in this circumstance.

In addition to more frequent and more persistent colonization of the lower airway rather аe the oropharynx, the other expression of tissue “tropisms” in the human respiratory tract may be that the lower airway becomes colonized by Pseudomonas species independent of the upper airway. In mechanically ventilated patients, Pseudomonas species, in contrast to other Gram-negative bacteria, have the capacity to colonize the lower airway without first colonizing the upper airway. This finding of primary tracheobron­chial colonization has been observed by several inves­tigators. Schwartz et al have reported that while Enterobacteriaceae entered the trachea after initial oropharyngeal colonization, other organisms such as Pseudomonas species rarely were found in the upper airway before colonizing the lower airway. Pingleton et al have also observed that intubated patients may have primary tracheal colonization by Gram-negative bacteria. canada drugs online

At least three different factors influence the adher­ence of bacteria to cells. These include host cell variables, bacterial variables, and micro-environmen­tal factors. Among host cell variables, the most important factors include the site of cellular origin and the type of host from which the cells are taken. Another cellular variable that may be important is the presence of cilia. Recently, it has been shown that Pseudomonas aeruginosa can bind directly to ciliary structures.

Bacterial variables are important because certain organisms have the capacity to bind epithelial cells while others do not. Specific features that enhance an organisms ability to bind to epithelial cells include the presence or absence of a capsule, the type of surface appendages present, and the nature of the exoproducts released by the bacteria. Certain Pseudomonas species do have the capacity to bind epithelial cells directly via their pili, which may serve as bacterial adhesions that attach directly to the epithelial surface.

The micro-environment in which bacteria meet epithelial cells is also a determinant of adherence. For example, the composition of sputum, both its protease and mucin components, can influence whether or not bacteria bind epithelial cells. In addition, the pH of the epithelial surface may influence the ability of bacteria to bind. As mentioned previously, proteo­lytic components of sputum may alter the bacterial binding interaction. Mucins in sputum can serve as receptors for bacterial binding and thus have the capacity to competitively inhibit bacterial binding if they bind to bacteria, but not directly to cells. On the other hand, if mucins attach directly the cellular surface, then they may act as a receptor “bridge” for bacteria and further increase the capacity of the epithelium to bind bacteria. This may be particularly important in patients who have impaired mucociliary clearance where large quantities of mucins may adhere to the epithelial surface and, thereby, predispose to colonization. kamagra soft tablets

Based on our understanding of bacterial adherence, it may become possible in the future to devise prophylactic strategies for airway colonization. As we better understand the nature of bacterial adherence, we may be able to develop vaccines with the use of adhesins as antigens and, thereby, form local antibody which can block bacterial binding. To the extent that mucins serve as cellular receptors for bacteria, the use of mucolytic or ciliokinetic agents may be helpful in modifying the risk of infection. In addition, our insight into bacterial adherence studies has shown that primary colonization of the lower airway by Pseudomonas aeruginosa is possible. Consideration of this finding may be useful in the design of protocols that employ prophylactic antibiotics. As Dr. Craven will discuss, many protocols that are designed to prevent nosocomial pneumonia involve sterilization of the oropharynx and the gastrointestinal tract, under the presumption that these are the only sources of organisms that enter the lung. If Pseudomonas aeru­ginosa can enter the tracheobronchial tree without first colonizing elsewhere, then prevention of infection by this organism may require the direct application of antibiotics to the lower airway, and not just to the oropharynx and gastrointestinal tract. Dr. Neiderman: Dr. Craven, can you discuss the scope and causes of the problem of nosocomial pneumonia? Dr. Craven: Nosocomial pneumonia accounts for ap­proximately 15 percent of hospital-acquired infec­tions and is the leading cause of death from nosocom­ial infection. Bates of nosocomial pneumonia are considerably higher in intensive care unit patients compared to patients on hospital wards, and mechan­ically ventilated patients have a risk of pneumonia that is several fold higher than nonventilated patients. Celis et al examined 120 consecutive episodes of nosocomial pneumonia and found intubation increased the risk of nosocomial pneumonia approximately 7­fold. Cross and Boupe found rates of pneumonia in patients receiving mechanical ventilation via an en­dotracheal tube were increased 10-fold compared to patients with no respiratory therapy device. In the Study on the Efficacy of Nosocomial Infection Control (SEN 1С), only 1 percent of the patients were treated with continuous ventilatory support, but the rate of pneumonia was 21-fold higher than patients who were not receiving mechanical ventilation.

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