byPseudomonas aeruginosaorAcinetobacterspp.; medical rather than surgical illnesses; and
ineffective antibiotic therapy (18–22).
VAP is the leading cause of both nosocomial mortality and morbidity. Secondary
bacteremia and empyema have been reported to occur in 4% to 38% and 5% to 8% of cases,
respectively. On an average, the hospital stay of VAP patients is extended for 4 to 13 days
(median 7.6 days). Current estimates indicate that this additional length of stay generates a cost
of $20,000 to $40,000 per case of HAP or VAP in the ICU. In Canada, VAP accounts for
approximately 17,000 ICU days per year or around 2% of all ICU days (23); the cost to the
health care system is CA $46 million.
PATHOGENESIS
The pathogenesis of HAP and VAP is linked to two separate, but related, processes:
colonization of the aerodigestive tract with pathogenic bacteria and aspiration of contaminated
secretions.
For VAP to occur, the delicate balance between host defenses and microbial invasion has
to be upset, allowing pathogens to colonize the lower respiratory tract (24).
In healthy subjects, the oropharynx is colonized by generally nonpathogenic micro-
organisms, includingStreptococcus viridans,Streptococcus pneumoniae, several anaerobes, and,
occasionally,Haemophilus influenza;yet, it is rare to find opportunistic gram-negative rods such
asP. aeruginosaandAcinetobacterspp. Several factors have been proposed to contribute to the
pathogenesis of VAP, such as the severity of the underlying disease, prior surgery, exposure to
antibiotics, and the use of invasive respiratory equipment (2,25–34). Oropharyngeal and
tracheal colonization byP. aeruginosaand enteric gram-negative bacilli have been related to
length of hospital stay and severity of the underlying disease (30).
The main route of VAP infection is oropharyngeal colonization by normal flora or by
exogenous pathogens acquired in the ICU. Typical sources of these pathogens are the hands of
medical staff or contaminated respiratory equipment, water, or air.
Once the oropharynx has been invaded, microorganisms may reach the lower respiratory
tract and lungs through several mechanisms. The main portals of bacterial entry into the lungs
areoropharyngeal pathogen aspirationor the leakage of bacteria-containing secretions around the
endotracheal cuff. The stomach and sinuses may act as potential reservoirs for nosocomial
pathogens colonizing the oropharynx, but their role is largely unknown and could depend on
the patient population or the changing natural history and management of VAP.
Microaspiration is common even in healthy individuals. Approximately 45% of healthy
subjects aspirate during sleep, and the rate of aspiration is higher in patients with reduced
levels of consciousness. Factors promoting aspiration include a generally reduced level of
consciousness, a diminished gag reflex, abnormal swallowing for any reason, delayed gastric
emptying, or decreased gastrointestinal motility. Reflux and aspiration of non-sterile gastric
contents is also a possible mechanism of pathogen entry into the lungs.
The risk of pneumonia is determined by the number and virulence of microorganisms
colonizing the oropharynx (35). Hospitalized patients may become colonized with aerobic
gram-negative bacteria within several days of admission, and as many as 75% of severely ill
patients will be infected within 48 hours (36). In addition, the near sterility of the stomach and
upper gastrointestinal tract may be disrupted by alterations in gastric pH due to illness,
medication, or enteric feeding. Much attention has, therefore, been paid to the possible
detrimental effects of ulcer prophylaxis regimens that raise the gastric pH (33,34).
Orotracheal intubation diminishes the natural defense mechanisms of the respiratory
tract, affecting mechanical factors (ciliated epithelium and mucus), humoral factors (antibody
and complement), and cell factors (polymorphonuclear leukocytes, macrophages, lympho-
cytes, and their respective cytokines).
The dorsal decubitus position is more conducive to microaspiration. The use of a
nasogastric tube obstructs the ostia of the facial sinuses. The sinuses may then act as an
infection reservoir from which organisms may seed the tracheobronchial tree (37–39).
The formation of a biofilm on the endotracheal tube could help sustain tracheal
colonization, and this mechanism is also thought to play a role in late-onset VAP caused by
resistant organisms.
Nosocomial Pneumonia in Critical Care 179